Intravenous nerve stimulation to promote volume return by splanchnic bed innervation

Abstract

Systems, devices, and methods for promoting a patient's volume return to the heart and cardiac pre-load by inducing constriction of at least a portion of the splanchnic bed of the patient are described herein. Constriction of at least a portion of the splanchnic bed is induced via electrical stimulation to splanchnic nerve fibers of one or more splanchnic nerves. Electrical stimulation to splanchnic nerve fibers is delivered using at least one intravenous electrode disposed within a vein of the patient proximate to the splanchnic nerve fibers.

Description

INTRAVENOUS NERVE STIMULATION TO PROMOTE VOLUME RETURN BY SPLANCHNIC BED INNERVATION

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 633,174, filed April 12, 2024, the entire content of which is incorporated herein by reference.

[0002] The present disclosure is directed to influencing organ function, and more specifically, systems, devices, and methods to influence the functioning of the splanchnic bed vasculature through stimulating splanchnic nerve fibers.SUMMARY

[0003] Embodiments described herein are directed to systems, devices, and methods to promote heart volume return and cardiac pre-load by activating neural pathways using neurostimulation, e.g., for managing orthostatic hypotension, postural orthostatic tachycardia syndrome (POTS), and symptoms thereof in patients. Generally, the illustrative systems, devices, and methods may be described as activating one or more splanchnic nerves by delivering stimulation to splanchnic nerve fibers using intravenous electrodes disposable within a vein of the patient. The vein may be one or more of an azygos vein, a side branch of an azygos vein, a hemiazygos vein, a side branch of a hemiazygos vein, a posterior intercostal vein, and a side branch of a posterior intercostal vein.

[0004] One illustrative system may include at least one intravenous electrode disposable within a vein of a patient to deliver electrical stimulation to splanchnic nerve fibers of the patient to activate one or more splanchnic nerves and a computing apparatus including at least one processor and operably coupled to the at least one intravenous electrode. The vein is one or more of an azygos vein, a branch site of an azygos vein, a hemiazygos vein, a branch site of a hemiazygos vein, a posterior intercostal vein, and a branch site of a posterior intercostal vein. The computing apparatus is configured to control the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers to activate constriction of splanchnic vasculature of the patient.

[0005] An illustrative implantable medical device may include at least one intravenous electrode disposable within a vein of a patient to deliver electrical stimulation tosplanchnic nerve fibers of the patient to activate one or more splanchnic nerves and a computing apparatus including at least one processor and operably coupled to the at least one intravenous electrode. The vein is one or more of an azygos vein, a branch site of an azygos vein, a hemiazygos vein, a branch site of a hemiazygos vein, a posterior intercostal vein, and a branch site of a posterior intercostal vein. The computing apparatus is configured to control the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers to activate constriction of splanchnic vasculature of the patient.

[0006] An illustrative method may include disposing at least one intravenous electrode within a vein of a patient and proximate to splanchnic nerve fibers of the patient to activate splanchnic nerves innervating at least a portion of the splanchnic bed of the patient and controlling electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers to activate constriction of splanchnic vasculature of the patient. The vein is one or more of an azygos vein, a branch site of an azygos vein, a hemiazygos vein, a branch site of a hemiazygos vein, a posterior intercostal vein, and a branch site of a posterior intercostal vein.

[0007] The at least one intravenous electrode may be disposed on a lead body. The lead body may include one or more of a cuff, a stent, a balloon-expandable stent, a selfexpandable stent, and a ring. The at least one intravenous electrode may include a plurality of individually controllable electrodes and controlling the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers may include controlling each electrode of the plurality of individually controllable electrodes in response to one or more of EMG measurements, ECAP measurements, side effect response metrics, and stimulation response metrics. The one or more splanchnic nerves may include one or more of the greater splanchnic nerve, the left greater splanchnic nerve, the right greater splanchnic nerve, the lesser splanchnic nerve, the left lesser splanchnic nerve, the right lesser splanchnic nerve, the lumbar splanchnic nerve, the left lumbar splanchnic nerve, and the right lumbar splanchnic nerve.

[0008] The system may further include at least one sensor, the device may further include at least one sensor, and the method may further include providing at least one sensor. The at least one sensor may be configured to monitor at least one physiological parameter of the patient. The computing apparatus may be further configured to monitor at least onephysiological parameter using at least one sensor. The method may further include monitoring at least one physiological parameter using at least one sensor. Controlling the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers may include controlling the electrical stimulation in response to the at least one monitored physiological parameter. The at least one sensor may include an implantable sensor. The at least one sensor may include the at least one intravenous electrode. The at least one sensor may include an implantable auxiliary electrode disposable proximate the patient’s heart. The implantable auxiliary electrode disposable proximate the patient’s heart may be configured to monitor impedance of the inferior vena cava. The at least one sensor may include at least one of an optical sensor configured to monitor a blood pressure of the patient and a membrane sensor configured to monitor a blood pressure of the patient. The at least one physiological parameter of the patient may include one or more of a posture, a body position, an activity level, a heart rate, a median R-wave to R-wave timing interval, an R-wave to R-wave variability, a thoracic impedance, an abdominal impedance, a thoracic impedance, an inferior vena cava impedance, a lung impedance, a temperature (e.g., a body temperature), and a blood pressure.

[0009] The system may further include a posture sensor, the device may further include a posture sensor, and the method may further include providing a posture sensor. The posture sensor may be configured to monitor a posture of the patient’s body between a supine position and an upright position. The computing apparatus may be further configured to monitor a posture of the patient’s body using a posture sensor. The method may further include monitoring a posture of the patient’s body using a posture sensor. Controlling the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers may include controlling the electrical stimulation in response to the monitored posture. Monitoring the posture of the patient’s body may include detecting a transition from a first position to a second position higher than the first position. Monitoring the posture of the patient’s body may include detecting a tilt of 60 degrees or greater, between 40 degrees and 90 degrees, or between 60 degrees and 90 degrees.

[0010] The electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers may have a pulse width of 210 mics, between 50 mics and 210mics, or between 210 mics and 1,000 mics. The electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers may have a frequency of 4 Hertz (Hz), 40 Hz, between 40 Hz and 60 Hz, or between 4 Hz and 100 Hz. Controlling the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers may include delivering electrical stimulation using the at least one intravenous electrode to splanchnic nerve fibers of one or more of the L1-L4 vertebrae, the T5-T11 vertebrae, and the T10-T11 vertebrae. The intravenous electrode may be disposable in the vein 25 mm or less from the patient’s spinal midline, between 1 mm and 5 mm from the splanchnic nerve fibers, or 2 mm or less from the splanchnic nerve fibers.

[0011] Controlling the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers may include adjusting one or more parameters of the electrical stimulation. The one or more parameters of the electrical stimulation may include one or more of pulse width, amplitude, frequency, on / off cycle timing, burst cycle timing, and pulse shape. The at least one intravenous electrode disposable with the vein of the patient to deliver stimulation to splanchnic nerve fibers of the patient to activate one or more splanchnic nerves may be configured to deliver stimulation to the splanchnic nerve fibers of the patient to activate the one or more splanchnic nerves innervating at least a portion of the splanchnic bed of the patient.

[0012] Another illustrative method may include disposing at least one intravenous electrode within a vein of a patient and proximate to splanchnic nerve fibers of the patient and causing delivery of electrical stimulation using the at least one intravenous electrode to the splanchnic nerve fibers. The vein is one or more of an azygos vein, a branch site of an azygos vein, a hemiazygos vein, a branch site of a hemiazygos vein, a posterior intercostal vein, and a branch site of a posterior intercostal vein. The electrical stimulation is configured to activate constriction of splanchnic vasculature of the patient and thereby promote volume return to the heart.

[0013] Yet another illustrative method may include disposing at least one intravenous electrode within a vein of a patient and proximate to splanchnic nerve fibers of the patient and causing delivery of electrical stimulation using the at least one intravenous electrode to the splanchnic nerve fibers, thereby activating constriction of splanchnic vasculature of the patient and promoting volume return to the heart. The vein is one or more of an azygosvein, a branch site of an azygos vein, a hemiazygos vein, a branch site of a hemiazygos vein, a posterior intercostal vein, and a branch site of a posterior intercostal vein.

[0014] The above summary is not intended to describe each disclosed embodiment or every implementation of the present disclosure. The figures and the detailed description below more particularly exemplify illustrative embodiments.BRIEF DESCRIPTION OF DRAWINGS

[0015] The discussion below refers to the following figures, wherein the same reference number may be used to identify the similar / same component in multiple figures. However, the use of a number to refer to a component in a given figure is not intended to limit the component in another figure labeled with the same number. The figures are not necessarily to scale.

[0016] FIG. 1 A is a schematic diagram of the anatomical pathways of splanchnic nerve fibers.

[0017] FIG. IB is a sectional right anterior oblique view of a human abdominal cavity, showing splanchnic nerves and surrounding anatomy.

[0018] FIG. 2 is a diagram including an illustrative implantable system configured to deliver stimulation to splanchnic nerve fibers.

[0019] FIG. 3 is an enlarged sectional right anterior oblique view of the human abdominal cavity of FIG. IB, including an intravenous lead positioned in the azygos vein, e.g., that could be used in the system of FIG. 2.

[0020] FIGS. 4A and 4B are diagrammatic views of illustrative intravenous leads positioned within a vein to deliver stimulation to target splanchnic nerve fibers, e.g., that could be used in the system of FIG. 2.

[0021] FIGS. 5A and 5B are diagrammatic views of illustrative intravenous leads, e.g., that could be used in the system of FIG. 2.

[0022] FIG. 6 is a block diagram of an illustrative implantable system, e.g., for use with the intravenous leads of FIGS. 3-5B.

[0023] FIGS. 7 A and 7B are flow diagrams of illustrative methods of splanchnic nerve fiber stimulation, e.g., that could be performed or executed using the systems of FIGS. 2- 6.

[0024] FIG. 8 is a flow diagram of an illustrative method of splanchnic nerve fiber stimulation in response to one or more physiological parameters, e.g., that could be performed or executed using the systems of FIGS. 2-6 or as part of the methods of FIGS. 7 A and 7B.

[0025] FIG. 9 is a flow diagram of an illustrative method of stimulating splanchnic nerve fibers in response to a patient’s heart rate informed by the patient’s posture, e.g., that could be performed or executed using the systems of FIGS. 2-6 or as a part of the methods of FIGS. 7 A and 7B.

[0026] FIG. 10 is a flow diagram of an illustrative method of adjusting one or more parameters of electrical stimulation to splanchnic nerve fibers, e.g., that could be performed or executed using the systems of FIGS. 2-6 or as a part of the methods of FIGS. 7 A and 7B.DETAILED DESCRIPTION

[0027] In the following detailed description of illustrative embodiments, reference is made to the accompanying figures of the drawing which form a part hereof, and in which are shown, by way of illustration, specific embodiments which may be practiced. It is to be understood that other embodiments may be utilized, and structural changes may be made without departing from (e.g., still falling within) the scope of the present disclosure.

[0028] Illustrative systems, devices, and methods are described with reference to the figures of the drawings. It will be apparent to one skilled in the art that elements or processes from one embodiment may be used in combination with elements or processes of the other embodiments, and that the possible embodiments of such systems, devices, and methods using combinations of features set forth herein is not limited to the specific embodiments shown in the Figures or described herein. Further, it will be recognized that the embodiments described herein may include elements that are not necessarily shown to scale. Still further, it will be recognized that timing of the processes and the size and shape of various elements herein may be modified but still fall within the scope of the present disclosure.

[0029] Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder defined by an increase in heart rate of 30 beats per minute (BPM) within 10 minutes of a change in posture (e.g., during a change from a supine position to an upright position, orduring a head-up tilt test to at least 60 degrees) without an increase in activity level. The peripheral nervous system response to a postural change typically includes inducing constriction in the venous system of the patient’s legs. Because of peripheral denervation in patients with POTS, the autonomic nervous system does not induce enough vasoconstriction in the legs in response to a postural change, causing reduced volume return to the heart and a decrease in cardiac pre-load. The decrease in cardiac pre-load is typically overcompensated via hormone release, which leads to the sudden increase in heart rate, and may result in symptoms such as dizziness, chest pain, palpitations, and fatigue. The population of POTS patients is about 1 million in the United States, alone, and has been associated with long term COVID and autoimmunity diseases. POTS especially occurs in females of childbearing age.

[0030] Orthostatic hypotension is a type of low blood pressure that occurs after a postural change, such as from sitting or lying down to standing, which can result in dizziness, lightheadedness, and / or fainting. Upward postural changes, such as from sitting or lying down to standing, generally cause blood to collect, or pool, in the legs and abdomen, which may cause a blood pressure drop due to reduced volume return to the heart.

[0031] Illustrative systems, devices, and methods described herein may utilize splanchnic nerve fiber stimulation to activate vasoconstriction in the patient’s splanchnic bed, thereby promoting heart volume return / cardiac pre-load. The splanchnic capacitance veins contain about 25 % of a patient’s total blood volume. By stimulating splanchnic nerve fibers, one or more splanchnic nerves may be activated, thus innervating the splanchnic bed. By innervating the splanchnic bed, constriction of the splanchnic capacitance veins can be induced, resulting in greater volume return to the heart, and promoting cardiac pre-load.

[0032] Illustrative systems, devices, and methods described herein may be described as activating one or more splanchnic nerves (e.g., of greater splanchnic nerves (GSN) and / or of lesser splanchnic nerves) through electrical stimulation of the splanchnic nerve fibers to mimic the electrical activation signals of the one or more splanchnic nerves. The electrical stimulation may be delivered to the splanchnic nerve fibers, for example, by at least one electrode positioned proximate to the target splanchnic nerve fibers. In particular, the electrical stimulation may be delivered to the splanchnic nerve fibers by at least one intravenous electrode disposed, or disposable, within a venous site (e.g., a within a vein or a venous branch site) proximate to the target splanchnic nerve fibers, such as an azygosvein, a hemiazygos vein, or a posterior intercostal vein, or a branch site of an azygos vein, a branch site of a hemiazygos vein, or a branch site of a posterior intercostal vein. Stimulating splanchnic nerve fibers using intravenous electrodes disposed in a venous site proximate to the target splanchnic nerve fibers may advantageously afford easier placement of electrodes proximate to the target splanchnic nerve fibers. Furthermore, in accordance with one or more embodiments described herein, the shape and spread of a stimulation field of the intravenous electrodes be controlled, for example, to adjust the splanchnic nerve fibers stimulated, manage stimulation response, manage side effect response, and / or accommodate for non-optimal intravenous placement.

[0033] A schematic diagram of the anatomical pathways of splanchnic nerve fibers, is shown in FIG. 1 A. As shown, the anatomical pathways may be described as travelling, or extending, along the spinal column 110, e.g., from the left chain ganglia 112 and the right chain ganglia 114 down the spinal cord 111 to the coccygeal ganglia 116. As shown, the anatomical pathways include splanchnic nerve fibers of the greater splanchnic nerve 132, which may be described as travelling, or extending, from the T5-T9 vertebrae, along the spinal column 110, and peripherally travelling, or extending, to the celiac ganglion 118. The anatomical pathways further include splanchnic nerve fibers of the lesser splanchnic nerve 134, which may be described as travelling, or extending, from the T9-T12 vertebrae, along the spinal column 110, and peripherally travelling, or extending, to the celiac ganglion 118. From the celiac ganglion 118, the splanchnic nerve fibers may be described as travelling, or extending, peripherally to various portions of the patient’s abdominal anatomy, including the patient’s stomach 140, splanchnic vascular bed 142, liver 143, pancreas 144, adrenal gland 145, small intestine 146, superior mesenteric ganglion 119, and large intestine 147.

[0034] In general, splanchnic nerve fibers may be described as carrying, or transmitting, sensory signals from the splanchnic bed to the brain and carrying, or transmitting, control signals (e.g., affecting vasoconstriction of the splanchnic vasculature) from the brain to the splanchnic bed. The illustrative systems, devices, and methods described herein may be configured to deliver stimulation to the splanchnic nerve fibers using one or more electrodes positioned proximate to the splanchnic nerve fibers to induce vasoconstriction of the splanchnic vasculature. Stimulation of neurons of splanchnic nerve fibers activates the one or more splanchnic nerves, which innervates at least a portion of the splanchnicbed, leading to increased vasoconstriction and, subsequently, greater volume return to the heart, thus promoting cardiac pre-load.

[0035] A sectional right anterior oblique view of a human abdominal cavity is depicted in FIG. IB, showing splanchnic nerves and surrounding anatomy. As shown, the azygos vein 122 may be described as running up, or extending along, the right side of the thoracic vertebral column. The azygos vein 122 may be described as draining towards the superior vena cava. One or more portions of the azygos vein 122 may be described as being proximate to (e.g., intersecting with or extending lateral to) one or more portions of the splanchnic nerve fibers, such as one or more portions of the greater splanchnic nerve 132, one or more portions of the lesser splanchnic nerve 134, and / or one or more portions of the lumbar splanchnic nerve.

[0036] Compared to the azygos vein 122, the hemiazygos vein 124 is at the opposite side of the spinal column 110 and may be described as a tributary to the azygos vein 122. The hemiazygos vein 124 may be described as draining into the azygos vein 122 in the midthoracic level. Similarly to the azygos vein 122, one or more portions of the hemiazygos vein 124 may be described as being proximate to (e.g., intersecting with or extending lateral to) one or more portions of the splanchnic nerve fibers, such as one or more portions of the greater splanchnic nerve 132, one or more portions of the lesser splanchnic nerve 134, and / or one or more portions of the lumbar splanchnic nerve.

[0037] One or more of the posterior intercostal veins 126 (one labeled in FIG. IB) may be described as draining into the azygos vein 122 or the hemiazygos vein 124. Similarly to the azygos vein 122 and the hemiazygos vein 124, one or more portions of the posterior intercostal veins 126 may be described as proximate to (e.g., intersecting with or extending lateral to) one or more portions of the splanchnic nerve fibers, such as one or more portions of the greater splanchnic nerve 132 and / or one or more portions of the lesser splanchnic nerve 134.

[0038] The greater splanchnic nerve 132 may be described as extending through the diaphragm into the abdominal cavity and along the thoracic vertebral column. The lesser splanchnic nerve 134 may be described as extending laterally to (e.g., parallel to, nearly parallel to, or alongside) the greater splanchnic nerve 132. The illustrative systems, devices, and methods described herein may be configured to deliver stimulation using intravenous electrodes disposed in one or more of the azygos vein 122, the hemiazygosvein 124, and / or the posterior intercostal vein 126, or a branch site of one of those, to splanchnic nerve fibers of one or more of the greater splanchnic nerve 132, the lesser splanchnic nerve 134, or the lumbar splanchnic nerve (not shown).

[0039] For example, electrical stimulation of the patient’s splanchnic nerve fibers may be controlled and administered by an implantable system implanted in a patient. A diagrammatic view of an illustrative implantable system 100 configured to deliver electrical stimulation to the splanchnic nerve fibers of a patient 104 is depicted in FIG. 2. The implantable system 100 may include a device 102 and at least one lead 106 electrically coupled to the device 102. The implantable system 100 may be configured as an electrical stimulator that generates and delivers electrical stimulation to the patient 104 via one or more electrodes arrayed on the lead 106. Although the implantable system 100 shown in FIG. 2 includes one lead 106, it is to be understood that illustrative systems, devices, and methods described herein may include two leads or more than two leads (e.g., one lead, two or more leads, three or more leads, a plurality of leads, etc.).

[0040] The implantable system 100 may be a chronic system configured to remain implanted within the patient 104 on the order of days to years. Conversely, the implantable system 100 may be a temporary or trial system used to screen or evaluate the efficacy of electrical stimulation. The lead 106 may be positioned in a vein (e.g., the azygos vein, the hemiazygos vein, or the posterior intercostal vein) proximate to the target splanchnic nerve fibers to deliver stimulation to the target splanchnic nerve fibers. As shown in FIG. 2, the lead may be positioned in the azygos vein (not shown in detail in FIG. 2) proximate the patient’s spinal column 110 to deliver stimulation to the splanchnic nerve fibers, as will be described further herein.

[0041] In addition to electrical stimulation, the implantable system 100 may also be configured to generate and deliver control pulses configured to elicit (e.g., trigger or initiate) evoked compound action potential (ECAP) signals. The control pulses may not stimulate the splanchnic nerve fibers to activate one or more splanchnic nerves. Additionally, in one or more embodiments, one or more of the electrodes of the lead 106 can be configured to sense an ECAP in response to the stimulation pulses. The stimulation pulses may or may not stimulate the splanchnic nerve fibers to activate one or more splanchnic nerves, and the sensed ECAP response may facilitate measuring the efficacy of the applied pulses.

[0042] The electrodes of the lead 106 may additionally or alternatively be configured to sense electromyographic (EMG) data / measurements, for example, to measure side effects such as muscle contractions or shivering. EMG data / measurements may also be measured with external (e.g., skin-worn) electrodes, such as in a clinical programming session or during an operating room procedure to implant the implantable system 100.

[0043] Additionally or alternatively to the electrodes for stimulation of the splanchnic nerve fibers, one or more additional electrodes (i.e., not the same electrodes used for stimulation) for sensing may be operably coupled to the implantable system 100 (e.g., via the lead 106 or via additional leads) and positioned (e.g., implanted in the tissue of the patient or placed on the skin of the patient) to sense the ECAP or EMG to the stimulation pulses. The one or more additional electrodes for sensing may be positioned in any suitable location. Suitable sensing electrode locations may include, for example, proximate the same splanchnic nerve fibers as a corresponding stimulating electrode or proximate the patent’s spinal column 110 (e.g., upstream or downstream of one or more corresponding electrodes for stimulating), or in other tissues known to exhibit stimulation side effects. As described herein, any electrode, including the electrodes used for stimulation, may operate as a sensing electrode.

[0044] In some embodiments, the lead 106 may include a lead body, which may be, for example, a cuff, a ring, or a stent. The lead body may be implanted into the target vein near the target splanchnic nerve fibers using any suitable technique, (e.g., methods, devices, etc.). For example, the lead 106 may be inserted into the femoral vein and navigated through the venous system to the target vein near the target splanchnic nerve fibers. The lead 106 may be delivered, for example, using a delivery system including an outer catheter and an inner elongate member slidably disposed within the outer catheter. The outer catheter may extend from a proximal end region to a distal end region, and may define a lumen extending therethrough. The outer catheter may be configured to navigate to the target vein site (e.g., via the patient’s venous system). The outer catheter may have any suitable length, outer diameter, flexibility, and pushability, each of which may be selected based on factors such as the inner diameter of the target vein site and the distance from a laparoscopic incision in the patient’s skin to the target vein site. In other words, suitable properties of the outer catheter may be selected such that the outer catheter issuitable to be navigated to the target venous site proximate to the target splanchnic nerve fibers.

[0045] The inner elongate member of the delivery system may be, or include, an inner catheter, or guidewire, extending from a proximal end region to a distal end region. In some embodiments, the inner elongate member is slidably disposable within the outer catheter and configured to deliver (e.g., push) the lead 106 to the target vein site proximate the target splanchnic nerve fibers. For example, the lead 106 may be disposable at (e.g., couplable to or supported on) the distal end region of the inner elongate member. In one or more embodiments, such as embodiments where the lead 106 includes a balloonexpandable stent, the distal end region of the inner elongate member has a balloon coupled to the distal end region, and the lead 106 may be supported (e.g., couplable or disposable) thereon.

[0046] The lead 106 includes electrodes arrayed on the lead body, such as about the circumference of the lead body and / or down the length of the lead body. Two or more electrodes may be configured to provide stimulation, for example, by being electrically coupled to respective anodic and cathodic outputs of a pulse generator of the device 102. For an ECAP process, two or more different electrode segments (e.g., at a distal end of the lead) may be electrically coupled to sense the evoked response, with one electrode being utilized as an anode and the other as a cathode. The lead 106 may have any number of electrodes (e.g., up to or more than four) to allow for customizing the location of the stimulation and sensing. This customization can be performed electronically by the selection of different subsets of the electrodes for each function, for example, using a switching circuit.

[0047] For splanchnic nerve fiber stimulation, the lead 106 may be positioned in the target vein near the target splanchnic nerve fibers. In this configuration, portions of the stimulation electrodes (configured, for example, as ring electrodes) may be facing (e.g., adjacent to, or relatively close to) the target nerve fibers. The portions of the stimulation electrodes facing away from target nerve fibers may deliver (e.g., emit) stimulation into non-target tissue, and the part, or portion, of the sensing electrodes facing away from the target nerve fibers may receive electromagnetic impulses unrelated to the splanchnic nerve fiber stimulation.

[0048] Accordingly, in some embodiments described herein, directional electrodes may be configured to sense and emit electromagnetic fields over a first partial circumference of the lead, such that there is no respective sensing and emission along a second partial circumference at the same longitudinal location along the lead. In such embodiments, the second partial circumference is different than the first partial circumference (e.g., the partial circumferences may be non-overlapping). This may be achieved, for example, by segmenting the electrodes at each longitudinal location, or by covering parts of fully circumferential electrodes (e.g., ring electrodes) with an electrical insulator that suppresses emission / sensing along the covered portions. The segmented electrodes may be controlled, or controllable, to steer the resulting fields to stimulate the target splanchnic nerve fibers (e.g., to position a cathode towards the target structure and a corresponding anode away), for example, to account for non-optimal lead positioning. Further steering may be achieved, for example, by staggering directional electrodes with nondirectional electrodes. The segments of the directional electrodes may be individually controllable, or programmable, using different parameters (e.g., ping, synchronous, asynchronous, continuous, or discontinuous) to control the depth of field of the stimulation.

[0049] A diagrammatic view showing an intravenous lead 206 of the illustrative implantable system 100 of FIG. 2 with an intravenous electrode 208 disposed within a vein of a patient is shown in FIG. 3. As shown, the intravenous electrode 208 of the intravenous lead 206 may be disposed, or disposable, within a vein of the patient, such as the azygos vein 122, to deliver electrical stimulation to target splanchnic nerve fibers, such as splanchnic nerve fibers of the greater splanchnic nerve 132 (e.g., the left greater splanchnic nerve or the right greater splanchnic nerve), splanchnic nerve fibers of the lesser splanchnic nerve 134 (e.g., the left lesser splanchnic nerve or the right lesser splanchnic nerve), or splanchnic nerve fibers of the lumbar splanchnic nerve (e.g., the left lumbar splanchnic nerve or the right lumbar splanchnic nerve). Electrical stimulation may be delivered to the target splanchnic nerve fibers to activate one or more splanchnic nerves (e.g., the greater, lesser, or lumbar splanchnic nerves), thus innervating at least a portion of the splanchnic bed of the patient. It will be understood in light of this disclosure that any suitable splanchnic nerve fibers may be targeted, and that suitable target splanchnic nerve fibers may be selected based on factors, such as those described herein. In someembodiments, suitable target splanchnic nerve fibers may be selected based on generating the desired volume shift effect (e.g., increasing volume return to the patient’s heart).

[0050] While FIG. 3 shows the intravenous electrode 208 disposed within the azygous vein 122, the intravenous electrode 208 may additionally or alternatively be disposed, or disposable, within other suitable veins, such as the hemiazygos vein 124 or the posterior intercostal vein 126, as two examples. Additionally or alternatively, the intravenous electrode 208 may be disposed within suitable venous branch sites, such as branch sites of the azygous vein, the hemiazygos vein, and / or the posterior intercostal vein. Suitable venous sites for intravenous electrode placement may be selected based on factors such as proximity to the target nerve fibers, navigability, accessibility, stability of placement for the intravenous electrode, or inner diameter, as a few examples.

[0051] In some embodiments, the at least one intravenous electrode (e.g., the intravenous electrode 208) may be positioned in the patient’s vein a suitable distance from the target splanchnic nerve fibers. For example, the intravenous electrode 208 may be positioned a suitable distance from the target splanchnic nerve fibers of the patient’s greater splanchnic nerve. Suitable distances from the nerve fibers of the greater splanchnic nerve may be, for example, between 1 millimeter (mm) and 5 mm. In one embodiment, the intravenous electrode may be positioned 2 mm from the splanchnic nerve fibers of the greater splanchnic nerve. As further examples, suitable distances from the nerve fibers of the greater splanchnic nerve may be 1 mm or greater, 2 mm or greater, 3 mm or greater, 4 mm or greater, or 5 mm or greater, and / or 6 mm or less, 5 mm or less, 4 mm or less, 3 mm or less, 2 mm or less, or 1 mm or less. It will be understood in light of this disclosure that any suitable distance from the nerve fibers of the greater splanchnic nerve may be used and the disclosure is not limited in this regard. Furthermore, it will be understood that suitable distances from the nerve fibers of the greater splanchnic nerve may be selected based on factors, such as those described herein.

[0052] As another example, the intravenous electrode may be positioned a suitable distance from the splanchnic nerve fibers of the patient’s lesser splanchnic nerve. Suitable distances from the splanchnic nerve fibers of the lesser splanchnic nerve may be between 1 mm and 5 mm. In one embodiment, the intravenous electrode may be positioned 2 mm from the splanchnic nerve fibers of the lesser splanchnic nerve fibers. As further examples, suitable distances from the nerve fibers of the lesser splanchnic nerve may be 1 mm orgreater, 2 mm or greater, 3 mm or greater, 4 mm or greater, or 5 mm or greater, and / or 6 mm or less, 5 mm or less, 4 mm or less, 3 mm or less, 2 mm or less, or 1 mm or less. It will be understood in light of this disclosure that any suitable distance from the nerve fibers of the lesser splanchnic nerve may be used and the disclosure is not limited in this regard. Furthermore, it will be understood that suitable distances from the nerve fibers of the lesser splanchnic nerve may be selected based on factors, such as those described herein.

[0053] As yet another example, the intravenous electrode may be positioned a suitable distance from the splanchnic nerve fibers of the patient’s lumbar splanchnic nerve.Suitable distances from the splanchnic nerve fibers of the lumbar splanchnic nerve may be between 1 mm and 5 mm. In one embodiment, the intravenous electrode may be positioned 2 mm from the splanchnic nerve fibers of the lumbar splanchnic nerve. As further examples, suitable distances from the nerve fibers of the lumbar splanchnic nerve may be 1 mm or greater, 2 mm or greater, 3 mm or greater, 4 mm or greater, or 5 mm or greater, and / or 6 mm or less, 5 mm or less, 4 mm or less, 3 mm or less, 2 mm or less, or 1 mm or less. It will be understood in light of this disclosure that any suitable distance from the nerve fibers of the lumbar splanchnic nerve may be used and the disclosure is not limited in this regard. Furthermore, it will be understood that suitable distances from the nerve fibers of the lumbar splanchnic nerve may be selected based on factors, such as those described herein.

[0054] In one or more embodiments, the at least one intravenous electrode (e.g., the intravenous electrode 208) may be positioned in the patient's vein a suitable distance from the patient’s spinal midline, or spinal centerline. Suitable distances from the patient’s spinal midline may be, for example, less than 25 mm or between 10 mm and 35 mm.

[0055] In at least one embodiment, the at least one intravenous electrode (e.g., the intravenous electrode 208) may be positioned in the patient’s vein at a suitable vertebral level, or at suitable vertebral levels. Suitable vertebral levels may include, for example, one or more levels between LI and L4, between T5 and Ti l, and between T10 and Ti l. In one embodiment, the intravenous electrode may be positioned at the T10 vertebral level. In another embodiment, the intravenous electrode may be positioned at the T11 vertebral level. In still another embodiment, the intravenous electrode may be positioned at, or between, the T10 vertebral level and the T11 vertebral level.

[0056] Diagrammatic views of illustrative embodiments of an intravenous lead 206 (e.g., for use in the implantable system 100) positioned within a vein 120 to deliver electrical stimulation to target nerve fibers 130 are shown in FIGS. 4 A and 4B. In some embodiments, the intravenous lead 206 includes a lead body to support the electrodes. For example, the lead 206 may include a stent lead body 220 (e.g., an expandable stent), as shown in FIG. 4A. As another example, the lead 206 may include a cuff lead body 222, as shown in FIG. 4B.

[0057] The lead body (e.g., the stent lead body 220 or the cuff lead body 222) may have, or include, any suitable form, or configuration. Suitable lead bodies may be selected based on factors such as navigability, outer diameter (e.g., relative to the inner diameter of the venous site), or desired blood flow (e.g., past, through, or around the intravenous lead), as a few examples. Suitable lead body forms may be, or include, stent, ring, cuff, tubular, elongate, etc. In one embodiment, the lead body is a balloon-expandable stent. In another embodiment, the lead body is a self-expandable stent. The lead and the lead body may each include any suitable materials (e.g., coatings, embedded materials, etc.). Suitable materials may include, for example, anti-thrombogenic coatings or other coatings to improve biocompatibility. As another example, suitable materials may include echogenic markers, radiopaque markers, or other materials for use in navigating the lead body to the vein site. It will be understood in light of the present disclosure that any suitable lead body form, or configuration, may be used and the disclosure is not limited in this regard.Furthermore, it will be understood in light of the present disclosure that suitable lead body forms, or configurations, may be selected based on factors such as those described herein.

[0058] In some embodiments, the intravenous lead 206 includes one or more intravenous electrodes, which may have, or include, any suitable electrode configuration. The intravenous electrodes may be arrayed on the lead body (e.g., the stent lead body 220 or the cuff lead body 222). The intravenous electrodes may be configured as electrode pairs, as shown in FIGS. 4 A and 4B, in which each lead 206 includes a first electrode pair 210 (including electrodes 210A and 210B), a second electrode pair 212 (including electrodes 212A and 212 B), a third electrode pair (including electrodes 214A and 214 B), and a fourth electrode pair (including electrodes 216A and 216B). While each intravenous lead 206 is shown with four electrode pairs (i.e., a quadripolar configuration), each lead may have fewer, or more, electrodes. For example, a lead may have four to eight electrodes.For another example, a lead (e.g., the lead 206) may have a single electrode or two electrodes. Furthermore, while described herein primarily as pairs of electrodes, suitable electrode configurations may additionally or alternatively include individual electrodes, groupings of two electrodes, groupings of three electrodes, groupings of four or more electrodes, or combinations thereof. In some embodiments with multiple leads, each lead may have a different number of electrodes. It will be understood in light of the present disclosure that any suitable number of intravenous electrodes may be used, and the disclosure is not limited in this regard. Furthermore, it will be understood in light of the present disclosure that suitable numbers of intravenous electrodes may be selected based on factors such as those described herein.

[0059] In some embodiments, the intravenous electrodes (e.g., the electrodes 210A, 21 OB, 212A, 212B, 214A, 214B, 216A, 216B) may have, or define, different spacing configurations on, about, or along, the lead 206 / lead body. For example, as shown in FIGS. 4 A and 4B, the intravenous electrodes may be positioned circumferentially about a lead body (e.g., along the cuff lead body 222, along the stent lead body 220, etc.), axially along a lead body, or both.

[0060] Diagrammatic views of illustrative intravenous leads (e.g., for use with the system 100 of FIG. 2) including an elongate lead body 224 supporting intravenous electrodes having different spacing configurations are shown in FIGS. 5 A and 5B. In certain embodiments, the spacing between two electrodes in an electrode pair may be varied, as shown in FIG. 5 A. The splanchnic nerve fibers (e.g., of the greater splanchnic nerve 132) proximate to the intravenous lead 206 may be covered (e.g., stimulated) by four pairs of electrodes (e.g., the intravenous electrodes 210A and 210B, 212A and 212B, 214A and 214B, and 216A and 216 B).

[0061] In some embodiments, the spacing within each electrode pair may be varied, which may improve targeting stimulation of target splanchnic nerve fibers. For example, the electrodes 210A and 210B of the first electrode pair 210 are spaced a first distance di apart (measured, for example, from the center of electrode 210A to the center of electrode 210B) whereas the electrodes 212A and 212B of the second electrode pair 212 are spaced a second distance d2 apart (measured, for example, from the center of the electrode 212A to the center of the electrode 212B) where the first distance di and the second distance d2 are not equal (e.g., the first distance di may be greater than the second distance d2 or thesecond distance d2 may be greater than the first distance di). In one or more embodiments, the distances may be configured as a ratio of a distance between electrodes to a length of the lead, or to a number of electrodes arrayed on the lead body.

[0062] Any suitable intra-electrode spacing (e.g., spacing between pairs of an electrode, such as between the electrodes 210A and 21 OB of the first electrode pair 210) may be used. Suitable intra-electrode spacing may be selected based on factors, such as the size (e.g., width) of the targeted splanchnic nerve fibers, or the distance from the targeted splanchnic nerve fibers, as examples. The intra-electrode spacing may be affected by placement of electrodes of different sizes. Suitable intra-electrode spacing may be, for example, between 1 mm and 8 mm or between 4 mm and 6 mm. In one embodiment, the intra-electrode spacing may be approximately 5 mm. As further examples, suitable intra- electrode spacings may be 1 mm or greater, 2 mm or greater, 3 mm or greater, 4 mm or greater, 5 mm or greater, 6 mm or greater, 7 mm or greater, or 8 mm or greater, and / or 8 mm or less, 7 mm or less, 6 mm or less, 5 mm or less, 4 mm or less, 3 mm or less, 2 mm or less, or 1 mm or less. It will be understood in light of the present disclosure that any suitable intra-electrode spacing may be used, and the disclosure is not limited in this regard. Furthermore, suitable intra-electrode spacings may be selected based on factors such as those described herein.

[0063] Additionally or alternatively, lengths of electrodes may vary between electrodes along the length of the lead / lead body. For example, an electrode pair may have a longer electrode and a shorter electrode (i.e., shorter in the axial direction of an elongate lead body, or shorter in the axial direction along the vein).

[0064] In some embodiment, spacing variation may include variations in spacing between electrode pairs (i.e., inter-electrode spacing), as illustrated in FIG. 5B. Inter-electrode spacing may be described the space, or distance, between the second electrode of a first pair and a first electrode of a subsequent pair. For example, electrodes 210B and 212A are spaced apart by a distance ds along the elongate lead body 224, and electrodes 214B and 216A are spaced apart by a distance d4 along the elongate lead body 224, where the distance ds and the distance d4 are not equal.

[0065] Any suitable inter-electrode spacing may be used. Suitable inter-electrode spacing may be selected based on factors, such as the size (e.g., width) of the targeted splanchnic nerve fibers, or the distance from the targeted splanchnic nerve fibers, as examples.Suitable inter-electrode spacing may be, for example, between 1 mm and 8 mm or between 4 mm and 6 mm. In one embodiment, the inter-electrode spacing may be approximately 5 mm. As further examples, suitable inter-electrode spacings may be 1 mm or greater, 2 mm or greater, 3 mm or greater, 4 mm or greater, 5 mm or greater, 6 mm or greater, 7 mm or greater, or 8 mm or greater, and / or 8 mm or less, 7 mm or less, 6 mm or less, 5 mm or less, 4 mm or less, 3 mm or less, 2 mm or less, or 1 mm or less. Additionally or alternatively, the inter-electrode spacing may be configured as a ratio of a distance between electrode pairs to a length of the lead, or to a number of electrodes arrayed on the lead body. It will be understood in light of the present disclosure that any suitable interelectrode spacing may be used, and the disclosure is not limited in this regard.Furthermore, suitable inter-electrode spacing may be selected based on factors such as those described herein. It will be further understood in light of the present disclosure that inter-electrode spacing variations and intra-electrode spacing variations, such as those illustrated in FIGS. 4A, 4B, 5A, and 5B, may be used in any suitable combination.

[0066] Each electrode may have any suitable size, which may include, for example, any suitable diameter and / or any suitable length. Suitable electrode diameters may be, for example, between 1 mm and 3 mm or between 3 mm and 5 mm. In one embodiment, the electrode diameter may be approximately 1 mm. Suitable electrode lengths may be, for example, between 1 mm and 3 mm or between 3 mm and 5 mm. In one embodiment, the electrode length may be approximately 1 mm. It will be understood in light of the present disclosure that any suitable electrode size may be used and the disclosure is not limited in this regard. It will be further understood in light of the present disclosure that suitable electrode sizes may be selected based on factors, such as those described herein.

[0067] The varying inter- and intra-electrode spacings may be advantageous to accommodate varying distances between anatomical structures, such as where the targeted splanchnic neural structures and the veins for lead placement are separated by various distances, or to selectively target different nerves, or nerve side branches. For example, as illustrated in FIG. 3, the distance separating the azygos vein 122 from the splanchnic nerve fibers of the greater splanchnic nerve 132 may increase as the azygos vein 122 and the greater splanchnic nerve extend in the cephalad direction. The varying electrode spacings may additionally be advantageous due to differences between patients, such as differences in height between patients. In some embodiments, the spacing may be 3, 3, 2 spacing foran illustrative eight-contact lead, which could also anticipate migration by providing redundancy in 2 / 3 of the pairs. In other leads, two four-contact electrode clusters may protect against migration. As discussed herein, the electrodes may be individually controlled, or segments of a directional electrode may be individually controlled, for example, to configure multi-polar leads as mono-polar leads. As set forth, a lead may also include more than eight electrodes, which may provide additional spacing options. The electrodes are controlled by a control unit as part of an implantable system (e.g., the implantable system 100) discussed herein.

[0068] A block diagram of an illustrative implantable system 300 for use, e.g., with the implantable system 100 of FIG. 2, is shown in FIG. 6. As shown, the system 300 includes a computing apparatus, or a control unit, 301, which may be described as a self-contained unit that may be implanted within the patient or located externally. The system 300 further includes at least one lead 302 that is operably coupled to the computing apparatus 301 via a connector 304. The computing apparatus 301 may include any componentry configured to control electrical stimulation delivered using the at least one intravenous electrode (e.g., the intravenous electrode 208) to the splanchnic nerve fibers to activate constriction of splanchnic vasculature of the patient to promote volume return to the heart / cardiac preload according to the methods and processes described herein. The computing apparatus 301 may include, among other things, switching circuitry 306 that selectively couples electrodes 303 (and segments thereof, if so configured) arrayed on the lead 302 to individual circuit elements within the computing apparatus 301. Further, the computing apparatus 301 may include sensing circuitry 308 operatively coupled to the electrodes 303 via the switching circuitry 306 to receive signals, such as ECAP measurements or EMG measurements. Additionally or alternatively, the electrodes 303 may be coupled to stimulation circuitry 310 via the switching circuitry 306 to deliver electrical stimulation (e.g., signals, pulse waveforms, etc.) to target splanchnic nerve fibers using the electrodes 303.

[0069] The switching circuitry 306, sensing circuitry 308, and stimulation circuitry 310 may include analog processing circuitry such as preamplifiers, amplifiers, and filters, and any other electrical or electronic component so as to perform the methods and processes described herein. As the computing apparatus 301 may use digital signal processing, the computing apparatus 301 may utilize an analog-to-digital converter 311 and / or a digital-to-analog converter 312, which may facilitate digital signal processing via processors 314 (or at least one processor). The processor 314 may include any suitable combination of, or number of, central processing units, co-processors, digital signal processors, application specific integrated circuits, etc. The processor 314 may be coupled to memory 318, which may include any combination of volatile memory (e.g., random access memory) and nonvolatile memory (e.g., firmware, flash memory).

[0070] The system 300 may further include one or more sensors 342, such as pressure sensors, accelerometers, flow sensors, blood chemistry sensors, posture sensors, activity sensors, temperature sensors, or other suitable physiological sensors. The sensors 342 may be coupled to the computing apparatus 301 via the data interface 315, which may provide sensor signals to the processor 314. The sensor signals may be used by the processor 314 for detecting physiological events or conditions of a patient. For example, the computing apparatus 301 may monitor various physiological parameters (e.g., a patient’s blood pressure, activity level, posture, heart rate, median R-wave to R-wave timing interval (RR timing), R-wave to R-wave variability (RR variability), impedance, thoracic impedance, abdominal impedance, inferior vena cava impedance, lung impedance, respiration rate, abdominal fluid content or fluid content in thoracic tissue, pulmonary wedge pressure, etc.). In one or more embodiments, the sensors 342 include a posture sensor. The posture sensor may be configured, for example, to monitor a posture of the patient’s body, for example, between a horizontal position (e.g., a prone position or a supine position) and vertical position (e.g., an upright position or an erect position), or between a low position (e.g., crouching, kneeling, sitting, prostrate, squatting, bowing, leaning, lying, etc.) and an upright position (e.g., erect, standing, etc.). In other words, monitoring a posture of the patient's body may include detecting a transition from a first position to a second position higher than the first position, or with the patient’s chest / head farther from the ground than in the first position. As just a few examples, monitoring a posture of the patient’s body may include detecting a transition from sitting to standing, lying to sitting, kneeling to crouching, or lying to crouching. Monitored signals may be used, for example, to determine whether to deliver, adjust, terminate, or initiate splanchnic nerve fiber stimulation, as described herein.

[0071] The processor 314 may operate in response to instructions stored in the memory 318. The instructions may include a segment selection and configuration functionality 320,for example, to set up leads having one or more segmented electrodes. The instructions may also include splanchnic nerve fiber stimulation functionality 322 for controlling stimulation to the target splanchnic nerve fibers, as described further herein with reference to FIGS. 7A-10. The memory 318 may further store a variety of programmed-in operating mode and parameter values that may be used by the processor 314. The memory 318 may also be used for storing metrics / data compiled from sensed signals and / or relating to device operating history (e.g., abdominal impedance, posture, heat rate, etc. for use in delivering, adjusting, controlling, initiating, and / or terminating stimulation) and / or for communicating such data outside of the patient. Examples of metrics / data compiled from sensed signals and / or relating to device operating history may include, for example, parameters of electrical stimulation (e.g., frequency, sinusoidal current, voltage, pulse width, tonic or burst stimulation, uni- or multi-lateral stimulation, balance of multi-lateral stimulation, on / off cycle timing, etc.), stimulation response metrics (e.g., EMG data / measurements or ECAP data / measurements, impedance sensor measurements, blood pressure sensor measurements, etc.), side effect response metrics (e.g., EMG data / measurements, ECAP data / measurements, sensor measurements, etc.).

[0072] In some embodiments, the system 300 further includes an external programmer 317. The computing apparatus 301 may be able to be programmed or controlled via the external programmer 317. The external programmer 317 links with the data interface 315 of the device. The data interface 315 may facilitate communications via any combination of wireless media, wired media, optical media, etc. The external programmer 317 may send control instructions to the computing apparatus 301, add software / firmware to the computing apparatus 301, update software / firmware of the computing apparatus 301, and / or download data gathered by the computing apparatus 301.

[0073] In at least one embodiment, the computing apparatus 301 includes a self-contained power source 316 (e.g., one or more batteries, capacitors, generators, converters, etc.). The system 300 may include a wireless power transmitter operably coupled to the power source 316. The wireless power transmitter may be positioned (e.g., implanted) proximate to the electrodes 303 or the lead 302 and configured to wirelessly transmit power for delivering stimulation using the electrodes 303. Additionally or alternatively, the lead 302 may include its own lead power source, which may be charged using wireless power transmission from the wireless power transmitter. The lead power source may additionallyor alternatively be charged using any suitable technique, such as an intravenous catheter operably coupled to the lead 302 or a wireless charger positionable at an external surface of the patient’s skin proximate to the lead 302.

[0074] Different fiber types may have different responses to stimulation at low pulse widths and high amplitudes compared with high pulse widths and low amplitudes (e.g., represented by a strength-duration curve of a fiber type). Similarly, different fiber types may have different responses to simulation at high frequency compared with low frequency. The difference in responses between different fiber types may be used to selectively stimulate target, or intended, fibers or to selectively avoid stimulating nontarget, or unintended, fibers. By adjusting one or more of pulse width, amplitude, and frequency and comparing measured responses at each, pulse width, amplitude, and frequency may be configured to optimize simulation, such as to maximize the patient’s stimulation effect response and minimize the patient’s side effect response. In some embodiments, optimizing one or more of pulse width, amplitude, and frequency may include using a self-learning algorithm.

[0075] In one or more embodiments, ECAP may be used to determine a fiber type or fiber types responding to stimulation pulses. Determining fiber types responding may be used to adjust stimulation parameters to select the target fiber types. For example, the stimulation may be adjusted until the target fiber types respond to the adjusted stimulation. Such embodiments may include measuring a response latency of the ECAP signals to the stimulation pulses. The response latency may be measured, for example, by determining a duration, or time period, between stimulation delivered using a stimulating electrode (e.g., proximate to target splanchnic nerve fibers) and sensing of the stimulation using a corresponding sensing electrode (e.g., proximate the target splanchnic nerve fibers or proximate nerve fibers that are downstream of the target splanchnic nerve fibers).

[0076] The fiber type(s), or population(s), activated by the stimulation may be determined, or classified, based on the response latency and the known physical distance (e.g., distance of separation) between the stimulating electrode and the sensing electrode. For example, myelinated fibers may be described as having a faster signal (e.g., stimulation pulse) propagation (e.g., between about 10 meters per second (m / s) and 100 m / s or greater), and thus a lesser response latency. As another example, small unmyelinated fibers may be described as having slower signal (e.g., stimulation pulse) propagation (e.g., betweenabout 0.5 m / s and 10 m / s), and, thus, a greater response latency. Target splanchnic nerve fibers of the greater splanchnic nerve may be described as sympathetic myelinated nerve fibers. Target splanchnic nerve fibers of the lesser splanchnic nerve may be described as sympathetic myelinated nerve fibers. Target splanchnic nerve fibers of the lumbar splanchnic nerve may be described as sympathetic myelinated nerve fibers.

[0077] The speed of propagation of different fiber types may be used to determine which fiber types are activated by electrical stimulation using certain stimulation parameters. For example, a stimulating electrode (e.g., positioned proximate the targeted splanchnic nerve fibers) may deliver a first series of one or more stimulation pulses and a sensing electrode (e.g., positioned proximate nerve fibers that are downstream of the targeted splanchnic nerve fibers) may thereafter sense the first series of one or more stimulation pulses, and the time delay between the delivery and the sensing of the pulses may be measured, or determined, as a first response latency. If the determined first response latency is not characteristic of the targeted splanchnic nerve fibers (e.g., the response latency is relatively low or relatively high, which may be described as uncharacteristic of splanchnic nerve fibers), one or more parameters of the stimulation may be adjusted. In an example, the determined first response latency may be relatively low (e.g., 30 milliseconds), which may be described as uncharacteristic of the target splanchnic nerve fibers (i.e., myelinated fibers), and one or more parameters of the stimulation may be adjusted in response. Subsequently, the stimulating electrode may deliver a second series of one or more stimulation pulses, the sensing electrode may thereafter sense the second series of one or more stimulation pulses, and the second response latency may be determined.

[0078] If the determined second response latency is more characteristic of the targeted splanchnic nerve fibers than the determined first response latency, then the stimulation parameters may be further adjusted (e.g., to further tune the stimulation parameters) or the stimulation parameters may continue to be used (e.g., in stimulating the targeted splanchnic nerve fibers to activate one or more splanchnic nerves innervating at least a portion of the splanchnic bed of the patient to activate constriction of splanchnic vasculature of the patient to promote volume return / cardiac pre-load). On the other hand, if the determined second response latency is less characteristic of the targeted splanchnic nerve fibers than the determined first response latency, then the stimulation parameters may be adjusted (e.g., by reversing the previous adjustment or by adjusting differentparameters) and the response latency of subsequent series of one or more pulses may be determined.

[0079] In one or more embodiments, if the latency response indicates, or suggests, that multiple fiber types are responding to the simulation pulses, the stimulation parameters may be adjusted, for example, to enhance the amplitude, or signal strength, of the ECAP signal(s) characteristic of the target (i.e. desired or intended) fiber types (e.g., the preganglionic dorsal root fibers or the renal afferent nerve fibers) and minimize the amplitude of the ECAP signal(s) characteristic of non-target (i.e., non-desired or nonintended) fiber types. In other words, while adjusting the stimulation parameters may not eliminate response, or stimulation, of non-target fibers, adjusting the stimulation parameters may thereby adjust, or shift, the ratio of responding target fibers to responding non-target fibers.

[0080] The ECAP measurements can be used to adjust the stimulation (e.g., pulse width, amplitude, frequency, on / off cycle timing, etc.) to improve the efficacy of the stimulation, such as by improving selectivity of stimulation (e.g., greater stimulation of target, or intended, fibers and reduced stimulation of non-target, or unintended, fibers). The measurement of the ECAP response allows for, among other things, the manual or automatic adjustment of the stimulation delivered using a system (e.g., the implantable system 100 or the implantable system 300) to compensate for changing conditions over the life of the system and patient. Examples of changing conditions may include, for example, shifting of position or orientation of a lead within the patient’s body, postural changes of the patient, or changing physiology of the patient.

[0081] The ECAP measurements may additionally or alternatively be used to position the electrodes arrayed on a lead, such as during an operation to implant one or more electrodes. For example, one or more of the ECAP amplitude, morphology (e.g., shape of the signal), and latency may be measured, or monitored, during placement of a stimulating electrode during surgery. When the one or more ECAP measurements indicate that the stimulating electrode being placed is configured to stimulate the target fiber population (e.g., splanchnic nerve fibers), positioning of the stimulating electrode may be finalized.

[0082] In one or more embodiments, a health care professional placing, or implanting, a lead may advance the lead through the vein (e.g., the azygos vein). While advancing, ECAP measurements may be received in response to stimulation by an electrode on theleady / lead body, and the ECAP measurements may be presented to the health care professional (e.g., visually on a display). The health care professional may advance the lead to find a position corresponding to, or providing, ECAP measurements that indicate that the stimulating electrode is proximate to and activating the target splanchnic nerve fibers (e.g., of the greater splanchnic nerve, of the lesser splanchnic nerve, etc.).

[0083] Stimulation parameters used to stimulate the target splanchnic nerve fibers may be controlled or adjusted, for example, in response to one or more physiological parameters of the patient, or changes to physiological parameters of the patient, such as one or more of a body position, a posture, an activity level, a heart rate, a median R-wave to R-wave timing interval, an R-wave to R-wave variability, a thoracic impedance, an abdominal impedance, a thoracic impedance, an inferior vena cava impedance, a lung impedance, a temperature (e.g., a body temperature), or a blood pressure. Additionally or alternatively, stimulation parameters used to stimulate the target splanchnic nerve fibers may be controlled or adjusted such that the electrical stimulation avoids stimulating non-target, or non-intended, fibers. For example, a characteristically high percentage of the target splanchnic nerve fibers may be described as tonic, such that the stimulation may be described in terms of stimulation waves that have, or define, a tonic form. The tonic stimulation may involve low frequencies, such as between 4 hertz (Hz) and 100 Hz or between 40 Hz and 60 Hz, as examples. In one embodiment, the tonic stimulation may have a frequency of 4 Hz. In another embodiment, the tonic stimulation may have a frequency of 40 Hz. In one or more embodiments, the tonic stimulation may have a frequency of 3 Hz or greater, 4 Hz or greater, 10 Hz or greater, 20 Hz or greater, 30 Hz or greater, 50 Hz or greater, 65 Hz or greater, 80 Hz or greater, or 100 Hz or greater, and / or 110 Hz or less, 100 Hz or less, 80 Hz or less, 65 Hz or less, 50 Hz or less, 30 Hz or less, 20 Hz or less, 10 Hz or less, or 4 Hz or less. Additionally or alternatively, tonic stimulation may be delivered continuously with regular periodic pulses, in bursts of pulses with periods of no stimulation, and / or continuously with irregular timing (e.g., random, pseudo random, stochastic timing variation, etc.) between pulses.

[0084] Another illustrative parameter for electrical stimulation delivered to the splanchnic nerve fibers may include pulses of controlled current, for example with a square waveform. Suitable pulse amplitude currents may be, for example, between 0.1 milliamps (mA) and 0.3 mA or between 0.3 mA and 1 mA. In one embodiment, the pulse amplitudecurrent may be approximately 0.2 mA. As further examples, suitable pulse amplitude currents may include 0.1 mA or greater, 0.2 mA or greater, 0.3 mA or greater, 0.4 mA or greater, 0.5 mA or greater, 0.6 mA or greater, 0.7 mA or greater, 0.8 mA or greater, 0.9 mA or greater, or 1 mA or greater, and / or 1 mA or less, 0.9 mA or less, 0.8 mA or less, 0.7 mA or less, 0.6 mA or less, 0.5 mA or less, 0.4 mA or less, 0.3 mA or less, 0.2 mA or less, or 0.1 mA or less. It will be understood in light of the present disclosure that any suitable pulse amplitude current may be used and the disclosure is not limited in this regard. Furthermore, suitable pulse amplitude currents may be selected based on factors, such as those described herein.

[0085] Yet another illustrative parameter for electrical stimulation delivered to the splanchnic nerve fibers may include a voltage amplitude. Voltage- and current-controlled stimulation may be delivered as continuous sinusoidal wave forms or discrete stimulation pulses. Suitable voltage amplitudes may be, for example, between 1 volt (V) and 8 V. As further examples, suitable voltage amplitudes may include 1 V or greater, 2 V or greater, 3 V or greater, 4 V or greater, 5 V or greater, 6 V or greater, 7 V or greater, or 8 V or greater, and / or 8 V or less, 7 V or less, 6 V or less, 5 V or less, 4 V or less, 3 V or less, 2 V or less, or 1 V or less. It will be understood in light of the present disclosure that any suitable voltage amplitude may be used and the disclosure is not limited in this regard. Furthermore, suitable voltage amplitudes may be selected based on factors, such as those described herein.

[0086] Still another illustrative parameter for electrical stimulation delivered to the splanchnic nerve fibers may include a pulse frequency. Suitable pulse frequencies may be, for example, between 5 Hz and 10 Hz or between 10 Hz and 100 Hz. In one embodiment, the pulse frequency may be approximately 40 Hz. As further examples, suitable pulse frequencies may include 5 Hz or greater, 6 Hz or greater, 7 Hz or greater, 8 Hz or greater, 9 Hz or greater, 10 Hz or greater, 25 Hz or greater, 50 Hz or greater, 75 Hz or greater, or 100 Hz or greater, and / or 100 Hz or less, 75 Hz or less, 50 Hz or less, 25 Hz or less, 10 Hz or less, 9 Hz or less, 8 Hz or less, 7 Hz or less, 6 Hz or less, or 5 Hz or less. It will be understood in light of the present disclosure that any suitable pulse frequency may be used and the disclosure is not limited in this regard. Furthermore, suitable pulse frequencies may be selected based on factors, such as those described herein.

[0087] Still yet another illustrative parameter for electrical stimulation delivered to the splanchnic nerve fibers may include a pulse width of each pulse. Suitable pulse widths may be, for example, between 50 microseconds (mics) and 210 mics or between 210 mics and 1,000 mics. In one embodiment, the pulse width may be 210 mics. As further examples, suitable pulse widths may include 40 mics or greater, 50 mics or greater, 60 mics or greater, 80 mics or greater, 100 mics or greater, 150 mics or greater, 200 mics or greater, 210 mics or greater, 250 mics or greater, 300 mics or greater, 400 mics or greater, 500 mics or greater, 700 mics or greater, or 1,000 mics or greater, and / or 1,200 mics or less, 1,000 mics or less, 700 mics or less, 500 mics or less, 400 mics or less, 300 mics or less, 250 mics or less, 210 mics or less, 200 mics or less, 150 mics or less, 100 mics or less, 80 mics or less, 60 mics or less, or 50 mics or less. It will be understood in light of the present disclosure that any suitable pulse width may be used and the disclosure is not limited in this regard. Furthermore, suitable pulse widths may be selected based on factors, such as those described herein.

[0088] In one or more embodiments, electrical stimulation delivered to the splanchnic nerve fibers may include one or more pulse trains. Pulse trains may be described as regular sequences of two or more pulses. In embodiments including delivery of electrical stimulation to the splanchnic nerve fibers that include pulse trains, parameters for electrical stimulation may include, for example, a number of pulses per train, a train amplitude (i.e., an amplitude of an individual pulse train), a train pulse amplitude (i.e., an amplitude of an individual pulse in a pulse train), a train frequency (i.e., a frequency of pulse trains in a period of time), a train pulse frequency (i.e., a frequency of pulses in an individual pulse train), a train width (i.e., a width of an individual pulse train), and / or a train pulse width (i.e., a width of an individual pulse in a pulse train), as a few examples. In embodiments including electrical stimulation delivered to the splanchnic nerve fibers that include one or more pulse trains, any suitable pulse train parameters, or combination of pulse train parameters, may be used. For example, any suitable train pulse frequency may be used, such as between 10 Hz and 100 Hz, between 10 Hz and 10 kHz, or between 15 Hz and 40 Hz. In one embodiment, the train pulse frequency is 20 Hz. As another example, any suitable train width may be used, such as between 0.05 milliseconds (ms) and 2 ms or between 0.5 ms and 1.5 ms. In one embodiment, the train width is 1 ms. As still another example, any suitable train amplitude current may be used, such as between0.1 mA and 10 mA or between 0.1 mA and 8 mA. In some embodiments, the train amplitude current is between 2 mA and 4 mA. It will be understood in light of the present disclosure that any suitable pulse train parameters may be used and the disclosure is not limited in this regard. Furthermore, suitable pulse train parameters may be selected based on factors, such as those described herein.

[0089] Other illustrative parameters for electrical stimulation delivered to the splanchnic nerve fibers may include, for example, synchronization (e.g., with multiple leads, electrodes, or electrode segments), and an on / off cycle, which may advantageously prevent battery drain, account for a wearing off time, and / or maintain the effect of stimulation over time.

[0090] When splanchnic nerve fiber stimulation is used to activate constriction of the splanchnic vasculature of the patient to promote volume return / cardiac pre-load, the stimulation parameters may at least start with initial settings and be adjusted as needed. Both positive and negative electrodes may be used, and the electrodes may be guided by x-ray or ultrasound guidance to the venous site proximate to the target splanchnic nerve fibers. The initial parameters may include, for example, one or more of amplitude (e.g., starting between 1 V and 8 V or starting at 1 V), pulse frequency (e.g., starting between 5 Hz and 100 Hz or starting at 5 Hz), tonic or burst stimulation, and pulse width (e.g., starting between 100 mics and 1,000 mics or starting at 100 mics). In certain embodiments, the initial parameters may be, or include an amplitude between 1 V and 8 V, a pulse frequency between 5 Hz and 100 Hz, a pulse width between 100 mics and 1,000 mics, and a tonic waveform.

[0091] In one or more embodiments according to this disclosure, the shape and spread of a stimulation field may be controlled, for example, to adjust the splanchnic nerve fibers stimulated, manage stimulation response, or manage side effect response. In some embodiments, an electrode may be configured to deliver multi-polar stimulation, which may help localize stimulation. For example, an electrode may be configured as a tri -pole with a cathode and two anodes (+ - +) (e.g., proximate to and spaced apart from the cathode or adjacent to the cathode) to contain the spread of the current flows from the cathode and fine tune the shape and spread of the stimulation field, such as to restrict stimulation of fibers other than the target splanchnic nerve fibers. Electrodes may additionally or alternatively include unbalanced multi-polar configurations. For example,an unbalanced tri-polar electrode may be configured with 75 % of anodal current on an upstream (e.g., caudal) electrode and 25 % of anodal current on a downstream (e.g., cephalad) electrode (i.e., 75 %+, 100 %-, 25 %+). For another example, a multi-polar electrode may be configured with the cathodes unbalanced (e.g., 50 %+, 25 %-, 75 %-, 50 %+) to further fine tune the shape and spread of the stimulation field. In still another example, both the anodes and the cathodes may be unbalanced.

[0092] A flow diagram of an illustrative method 400 of splanchnic nerve fiber stimulation to activate constriction of the splanchnic bed vasculature of the patient to promote volume retum / cardiac pre-load (e.g., that may be performed or executed by the systems of FIGS. 2-6), is depicted in FIG. 7A. When a patient, such as a patient managing symptoms of POTS, undergoes a postural change 402, the patient may experience blood pooling away from the heart, such as blood pooling in the legs 404, which leads to reduced volume return and a decrease in cardiac pre-load 406. The decrease in cardiac pre-load 406 may cause an overcompensated release of hormones 408, which causes a sudden increase in heart rate 410. The overcompensated release of hormones 408 and the sudden increase in heart rate 410 may cause symptoms such as dizziness, chest pain, palpitations, and fatigue.

[0093] As described herein, electrical stimulation may be delivered to the splanchnic nerve fibers 414 of the patient to mimic activation signals of the splanchnic nerves, thus activating one or more splanchnic nerves 416 to induce splanchnic bed vasoconstriction 418. The splanchnic bed vasoconstriction 418 causes increased blood volume return to the heart 420 from the splanchnic bed vasculature, increasing cardiac pre-load 422, thus reducing, or minimizing, the heart rate increase and overcompensated hormone release. As described herein, physiological parameters may be measured or monitored 412 (e.g., impedance, heart rate, blood pressure, etc.) to determine whether or when splanchnic nerve stimulation should be administered, as discussed further below.

[0094] A flow diagram of an illustrative method 450 of splanchnic nerve fiber stimulation to activate constriction of the splanchnic bed vasculature of the patient to promote volume return to the heart (e.g., that may be performed or executed by the systems of FIGS. 2-6), is depicted in FIG. 7B. When a patient, such as a patient managing symptoms of orthostatic hypotension, undergoes a postural change 452, the patient may experience blood pooling away from the heart, such as blood pooling in the legs / abdomen 454, whichleads to a decrease in blood pressure 456. The decrease in blood pressure 456 may cause symptoms such as dizziness, lightheadedness, or fainting.

[0095] As described herein, electrical stimulation may be delivered to the splanchnic nerve fibers 460 of the patient to mimic activation signals of the splanchnic nerves, thus activating one or more splanchnic nerves 462 to induce splanchnic bed vasoconstriction 464. The splanchnic bed vasoconstriction 464 causes blood volume return to the heart 466 from the splanchnic bed vasculature, which increases blood pressure 468, thus reducing, or minimizing, symptoms such as dizziness, lightheadedness, or fainting. As described herein, physiological parameters may be measured or monitored 458 (e.g., impedance, heart rate, blood pressure, etc.) to determine whether or when splanchnic nerve stimulation should be administered, as discussed further below.

[0096] A flow diagram of an illustrative method 500 of stimulating splanchnic nerve fibers in response to one or more physiological parameters is shown in FIG. 8. At least one physiological parameter of a patient is determined 502 (e.g., measured, monitored, determined from measurement data, etc.). The at least one physiological parameter could include one, two, or more physiological, or physical, parameters such as, for example, a patient’s posture, respiration rate, abdominal fluid content, impedance in various regions of the body (e.g., thoracic impedance, abdominal impedance, inferior vena cava impedance, lung impedance, etc.), ratios of impedance between body regions, systolic blood pressure (SBP), diastolic blood pressure (DBP), aortic blood pressure, venous blood pressure, brachial blood pressure, finger blood pressure, blood oxygen level (e.g., blood oxygen concentration), a temperature (e.g., a body temperature), blood flow (e.g., aortic flow, vascular flow, etc.), physiologic nerve excitation spiking (e.g., at the intravenous electrode, between the intravenous electrode and an auxiliary electrode, etc.), or rates of change thereof. One or more of the physiological parameter values may be compared with a selected threshold value 504 that represents a point at which either splanchnic nerve fiber stimulation for a patient should be started (e.g., initiated, triggered, etc.), or in the case of ongoing splanchnic nerve fiber stimulation, the splanchnic nerve fiber stimulation should be adjusted (e.g., by increasing stimulation parameters, decreasing stimulation parameters, terminating stimulation, etc.).

[0097] In one or more embodiments according to the illustrative method 500, if it is determined that splanchnic nerve fiber stimulation does not need to be adjusted or startedbased on the comparison to selected threshold values, the method may return to measuring one or more physiological parameters 502.

[0098] If the comparison to selected threshold values determines that splanchnic nerve fiber stimulation needs to be started or adjusted (e.g., a physiological parameter equals or exceeds a selected threshold value), splanchnic nerve fiber stimulation is initiated 506 (or adjusted). As discussed herein, splanchnic nerve fiber stimulation may involve stimulating splanchnic nerve fibers of one or more of the greater splanchnic nerve, the lesser splanchnic nerve, and the lumbar splanchnic nerve. In certain embodiments, if a single physiological parameter exceeds a predetermined threshold, the splanchnic nerve fibers are stimulated. In other embodiments where two or more physiological parameters are determined, stimulation may be initiated if only one, only two, only certain designated, or all parameters exceed one or more respective predetermined threshold values. Stimulation is continued until one or more designated physiological parameters no longer exceed the predetermined threshold value(s). In some embodiments, the same physiological parameter, or the same set of physiological parameters, is used to initiate and halt splanchnic nerve fiber stimulation. Additionally or alternatively, a first physiological parameter, or a first set of physiological parameters, may be used to initiate splanchnic nerve fiber stimulation and a different second physiological parameter, or a different second set of physiological parameters, may be used to halt splanchnic nerve fiber stimulation.

[0099] In some embodiments according to the illustrative method 500, if one or more of the physiological, or physical, parameters do not exceed (or no longer exceed) a threshold, stimulation is stopped 508. In this context, the term exceed means to go beyond the limits of, which in certain embodiments, may mean to increase above, or decrease below a threshold value. In certain embodiments, if a single parameter does not exceed a predetermined threshold, stimulation may be stopped. In other embodiments where two or more parameters are determined, stimulation may be stopped if only one, only two, only certain designated, or all parameters do not exceed one or more predetermined levels. In some embodiments, the stimulation may be stopped after a predetermined duration, or time period. Additionally or alternatively, the stimulation may be stopped after a predetermined number of pulses or after a predetermined number of pulse trains. The predetermined threshold may be determined for a designated demographic or personalizedfor each patient. For example, the selected threshold or parameters may be determined through a self-learning algorithm to improve, or optimize, conditions for initiating or altering splanchnic nerve fiber stimulation based on a subset of non-overlapping parameters.

[0100] In at least one embodiment, a first parameter, or a first set of parameters, (e.g., posture / postural change and / or activity level) may inform how / when to stimulate based on a second parameter, or a second set of parameters (e.g., heart rate and / or impedance). A flow diagram of an illustrative method 550 of stimulating splanchnic nerve fibers in response to a patient’s heart rate informed by the patient’s posture is shown in FIG. 9. The patient’s posture (i.e., a first physiological parameter) is determined 552 (e.g., measured, monitored, determined from measurement data, etc.), and the determined posture may be compared with a selected posture threshold value 554, for example, to determine whether a degree, or amount, of postural change over a time period has exceeded the selected postural threshold value. If it is determined that the posture, or change in posture, does not exceed the selected postural threshold value, the method 550 may return to determining the patient’s posture 552. As an example, the selected postural threshold value may be a change in tilt of 30 degrees or more in a 10-second period; if it is determined that the patient’s posture has changed in tilt from 0 degrees to 15 degrees (such as when a patient rises to her elbows from a fully prone position, for example) in a 10 second period, which is less than (i.e., does not exceed) the selected postural threshold value, then the method 550 may return to determining the patient’s posture.

[0101] In one or more embodiments according to the illustrative method 550, if it is determined that the patient’s posture, or change in posture over a time period, exceeds the selected postural threshold value, the method 550 includes determining the patient’s heart rate 556 (i.e., a second physiological parameter). As an example, the selected postural threshold value may be a change in tilt of 30 degrees or more in a 10-second period; if it is determined that the patient’s posture has changed in tilt from 0 degrees to 90 degrees (such as when a patient rises from a fully prone position to a fully erect position) in a 10 second period, which is greater than (i.e., does exceed) the selected postural threshold value, then the method 550 may proceed to determining the patient’s heart rate 556.

[0102] The determined heart rate may be compared with a selected heart rate threshold value 558, for example, to determine whether the heart rate, or a change in the heart rateover a time period, has exceeded the selected heart rate threshold value. If it is determined that the heart rate, or change in heart rate, does not exceed the selected heart rate threshold value, the method 550 may return to determining the patient’s posture 552. As an example, the selected heart rate threshold value may be a 30 BPM increase in heart rate in a 10- second period; if it is determined that the patient’s heart rate has increased 10 BPM in a 10-second period, which is less than (i.e., does not exceed) the selected heart rate threshold value, then the method 550 may return to determining the patient’s posture 552. In one or more embodiments, the method 550 may continue determining the patient’s heart rate 556 for a pre-determined duration, or time period, after the patient’s determined posture has exceeded the selected postural threshold value.

[0103] In some embodiments according to the illustrative method 550, if it is determined that the patient’s heart rate, or change in heart rate over a time period, exceeds the selected heart rate threshold value, the method 550 may initiate splanchnic nerve fiber stimulation 560. As an example, the selected heart rate threshold value may be a 30 BPM increase in heart rate in a 10-second period; if it is determined that the patient’s heart rate has increased 35 BPM in a 10-second period, which is greater than (i.e., does exceed) the selected heart rate threshold value, then the method 550 may proceed to initiating splanchnic nerve fiber stimulation 560.

[0104] In at least one embodiment, the methods (e.g., the method 500) and systems (e.g., the system 100) described herein may include measuring, or determining, the patient’s blood pressure. Blood pressure may be measured using any suitable technique (e.g., methods, devices, sensors, etc.). Suitable blood pressure measurement techniques may include, for example, using an optical sensor, using a membrane sensor, using an implantable medical device such as an implantable cardiac monitor (e.g., LINQ from MEDTRONIC), using an external medical device such as an ankle band, finger pressure cuff, or arm cuff. It will be understood in light of the present disclosure that any suitable blood pressure measurement technique may be used and the disclosure is not limited in this regard. It will be further understood that suitable blood pressure measurement techniques may be selected based on factors, such as those described herein.

[0105] In one or more embodiments, stimulation delivered using the at least one intravenous electrode (e.g., the intravenous electrode 208) may be controlled based on selected thresholds for the patient’s systolic blood pressure (SBP), such as based onwhether the patient's SBP is less than a selected threshold value. Selected threshold values for the patient’s SBP may be, for example, between 60 millimeters of mercury (mmHg) and 100 mmHg. In one embodiment, the selected SBP threshold value may be 80 mmHg or less. As further examples, suitable selected SBP threshold values may be 100 mmHg or less, 90 mmHg or less, 85 mmHg or less, 80 mmHg or less, 75 mmHg or less, or 70 mmHg or less. It will be understood in light of the present disclosure that any suitable SBP threshold value may be used and the disclosure is not limited in this regard. It will be further understood that suitable SBP threshold values may be selected based on factors, such as those described herein.

[0106] In some embodiments, stimulation delivered using the at least one intravenous electrode (e.g., the intravenous electrode 208) may be controlled based on selected thresholds for the patient’s diastolic blood pressure (DBP), such as based on whether the patient's DBP is less than a selected threshold value. Selected threshold values for the patient’s DBP may be, for example, between 30 mmHg and 60 mmHg. In one embodiment, the selected DBP threshold value may be 40 mmHg or less. As further examples, suitable selected DBP threshold values may be 70 mmHg or less, 60 mmHg or less, 55 mmHg or less, 50 mmHg or less, 45 mmHg or less, 40 mmHg or less, 35 mmHg or less, or 30 mmHg or less. It will be understood in light of the present disclosure that any suitable DBP threshold value may be used and the disclosure is not limited in this regard. It will be further understood that suitable DBP threshold values may be selected based on factors, such as those described herein.

[0107] In at least one embodiment, stimulation delivered using the at least one intravenous electrode (e.g., the intravenous electrode 208) may be controlled based on selected thresholds for both the patient’s DBP and the patient’s SBP. For example, stimulation may be delivered based on a selected SBP threshold value of 80 mmHg or less and a selected DBP threshold value of 40 mmHg or less.

[0108] In one or more embodiments, the methods (e.g., the method 500) and systems (e.g., the system 100) described herein may include measuring, or determining, the patient's posture, or postural changes of the patient. The patient's posture, and changes thereof, may be measured using any suitable technique (e.g., methods, devices, sensors, etc.). Suitable posture measurement techniques may include, for example, using an activity sensor, a 3- axis accelerometer, a gyroscope, an implantable medical device such as an implantablecardiac monitor (e.g., LINQ from MEDTRONIC), or an external medical device such as an ankle band or a wrist sensor. It will be understood in light of the present disclosure that any suitable posture measurement technique may be used and the disclosure is not limited in this regard. It will be further understood that suitable posture measurement techniques may be selected based on factors, such as those described herein.

[0109] In some embodiments, stimulation delivered using the least one intravenous electrode (e.g., the intravenous electrode 208) may be controlled in response to the patient’s posture, such as in response to the patient’s posture exceeding a selected threshold value, or in response to a postural change exceeding a selected threshold value for postural changes. For example, stimulation may be delivered based on a measured change in the patient’s posture being greater than a selected threshold value in a time period, or a measured change in the patient’s posture between horizontal (e.g., supine or prone) and vertical (e.g., upright or erect) being greater than a selected threshold value. In one embodiment, monitoring the patient’s posture includes detecting sitting up (e.g., from a supine position) and / or standing up (e.g., from a supine position or from a sitting position). In such an embodiment, stimulation may be controlled in response to detecting that the patient’s posture has changed to sitting up or that the patient’s posture has changed to standing up.

[0110] In one or more embodiments, monitoring the patient’s posture includes detecting a tilt, which may be described as an angle defined between the patient’s body and the horizontal plane, such as an angle of 90 degrees when a patient is standing fully upright, or an angle of 0 degrees when the patient is supine, or laying fully down on the horizontal plane. Stimulation may be controlled in response to detecting a tilt greater than a selected tilt threshold value, or a change in tilt in a time period that is greater than a selected threshold value. For example, stimulation may be controlled (e.g., initiated) in response to, or based on, detecting a tilt between 40 degrees and 90 degrees or a tilt between 60 degrees and 90 degrees. In one embodiment, stimulation is controlled (e.g., initiated) in response to detecting a tilt of 60 degrees or greater. As further examples, simulation may be controlled in response to detecting a tilt of 30 degrees or greater, 40 degrees or greater, 50 degrees or greater, 60 degrees or greater, 70 degrees or greater, 80 degrees or greater, or 85 degrees or greater. It will be understood in light of the present disclosure that any suitable posture threshold value may be used and the disclosure is not limited in thisregard. It will be further understood that suitable posture threshold values may be selected based on factors, such as those described herein.[oni] In at least one embodiment, the methods (e.g., the method 500) and systems (e.g., the system 100) described herein may include measuring, or determining, the patient’s heart rate, or parameters of the patient's heart rate (e.g., median RR timing, RR variability, etc.). Heart rate may be measured using any suitable technique (e.g., methods, devices, sensors, etc.). Suitable heart rate measurement techniques may include, for example, using an implantable medical device such as an implantable cardiac monitor (e.g., LINQ from MEDTRONIC), using an external medical device such as an ankle band or activity sensor, using ECG measurements (e.g., from a smartwatch), using EMG measurements (e.g., from an implantable cardiac device), using peak selection on cyclic variation of pulse pressure, or using impedance waveform. It will be understood in light of the present disclosure that any suitable heart rate measurement technique may be used and the disclosure is not limited in this regard. It will be further understood that suitable heart rate measurement techniques may be selected based on factors, such as those described herein.

[0112] In one or more embodiments, the methods (e.g., the method 500) and systems (e.g., the system 100) described herein may include measuring, or determining, the patient’s impedance (e.g., thoracic impedance, abdominal impedance, etc.). Impedance may advantageously be indicative of blood pooling away from the heart, such as in the legs.

[0113] Impedance may be measured using any suitable technique (e.g., methods, devices, sensors, etc.). Suitable impedance measurement techniques may include, for example, using an implantable medical device such as an implantable cardiac monitor (e.g., LINQ from MEDTRONIC), using an external medical device such as an ankle band or a chest band, or using measurement from a conductance catheter (e.g., disposed in a blood vessel of the patient). Another suitable impedance measurement technique may be, or include, measuring the impedance between a lead (e.g., the intravenous lead 206) disposed in a vein of the patient (e.g., to deliver electrical stimulation to splanchnic nerve fibers) and an implantable medical device case (e.g., the computing apparatus 301) positioned elsewhere in the patient’s torso. Still another suitable measurement technique includes measuring impedance between a lead (e.g., the intravenous lead 206) disposed in a vein of the patient (e.g., to deliver electrical stimulation to splanchnic nerve fibers), an implantable medical device case positioned in the torso, and / or auxiliary leads supporting electrodes elsewherein the torso, such as an implantable auxiliary electrode disposed, or disposable, proximate to the patient’s heart and configured to monitor impedance of the inferior vena cava. Yet another suitable measurement technique includes using jugular vein intra- or extra- vascular ultrasound to measure filling, corresponding to impedance. Still yet another suitable impedance measurement technique includes measuring impedance between two or more electrodes (e.g., the electrodes 210, 212, 214, 216) arrayed on a lead body (e.g., the lead body 220). It will be understood in light of the present disclosure that any suitable impedance measurement technique may be used and the disclosure is not limited in this regard. It will be further understood that suitable impedance measurement techniques may be selected based on factors, such as those described herein.

[0114] In another example, two or more physiological parameters are used together, such as a patient’s posture and a thoracic fluid content shift. A patient’s thoracic fluid content shift can identify a measurement of a patient’s abdominal impedance as well as an indirect measurement of a patient’s subcutaneous impedance. For example, a patient’s intraabdominal pressure (IAP) may be measured to provide an estimate of the amount of splanchnic bed volume, which can be indicative of pooling blood. Additionally or alternatively, the impedance of the lungs may be measured. Impedance can be measured using a technique disclosed in U.S. Patent Application Publication No. 2018 / 0126172 entitled “Method and apparatus for monitoring tissue fluid content for use in an implantable cardiac device” and published May 10, 2018, which is incorporated herein by reference in its entirety.

[0115] In some embodiments, the physiological parameters are determined, or measured, in real time (e.g., every 5 seconds or every 10 seconds). The timing and frequency of measurements can be adjusted in accordance with a patient’s body position, posture, physical activity, heart rate, or respiration measured with a sensor (e.g., one or more of the sensors 342).

[0116] A flow diagram of an illustrative method 600 of adjusting, or titrating, one or more parameters of electrical stimulation to splanchnic nerve fibers in response to physiological is illustrated in FIG. 10. Parameters of electrical stimulation to splanchnic nerve fibers may include any suitable parameters such as, for example, frequency, sinusoidal current, voltage, pulse width, tonic or burst stimulation, uni- or multi-lateral stimulation, balance of multi-lateral stimulation, on / off cycle timing, etc. Electrical stimulation may bedelivered using at least one electrode to splanchnic nerve fibers 602 of one or more of the greater splanchnic nerve, the lesser splanchnic nerve, and the lumbar splanchnic nerve, e.g., using the systems and devices described herein with respect to FIGS. 2-6.

[0117] The method 600 includes receiving metrics, or data, related to at least one side effect response 604. The side effect response metrics may include, for example, sensed data from electrodes (e.g., EMG data / measurements or ECAP data / measurements, such as from the intravenous electrodes 208 or electrodes of the sensors 342), sensor measurements (e.g., from the sensors 342), or patient feedback (e.g., reporting perceived side effects). Side effect response metrics may be related to side effects such as, for example, shivering, muscle contractions, cramps (e.g., bowel cramps), pain, discomfort, heart rate, blood pressure, affected breathing (e.g., difficult breathing, such as due to muscle contractions), or sensory phenomenon (e.g., paresthesia).

[0118] Side effect response metrics may be used to determine whether to adjust one or more parameters 606 of the electrical stimulation delivered to the splanchnic nerve fibers. Side effect response metrics may indicate not to adjust stimulation parameters, for example, because all side effect responses are within an acceptable range (e.g., below a threshold perceived by the patient or below a hazard threshold value). Side effect response metrics may indicate to adjust stimulation parameters, for example, because one or more side effect responses are outside of an acceptable range (e.g., above a threshold tolerated by the patient or above a hazard threshold value). For example, a 0 % to 10 % increase in the patient’s SBP above a baseline SBP value may be within the acceptable range of side effect responses. In another example, a 0 % to 10 % increase in the patient’s blood glucose level above a baseline blood glucose value may be within the acceptable range of side effect responses.

[0119] The acceptable range, or threshold, for side effect responses may differ based on circumstances, such as whether the patient is receiving stimulation to address acute symptoms (e.g., in a hospital) or chronic symptoms (e.g., chronic POTS). For example, mild shivering may be within the acceptable range of side effect responses for a patient receiving stimulation to address acute symptoms, but mild shivering may be outside the acceptable range of side effect responses for a patient receiving stimulation chronically.

[0120] If side effect response metrics indicate to adjust stimulation parameters, one or more parameters of electrical stimulation may be adjusted 608. For example, if EMGdata / measurements indicates motor response (e.g., muscle contractions or shivering) is above a perception threshold of the patient, one or more parameters of stimulation may be adjusted to reduce stimulation (e.g., by reducing sinusoidal current or voltage). For another example, if ECAP data / measurements indicates non-target fibers are being stimulated above an acceptable threshold (e.g., the patient’s perception threshold), one or more parameters of stimulation (e.g., pulse width, amplitude, ratio of pulse width to amplitude to adjust sub-population of stimulated fibers based on the respective strengthduration curve) may be adjusted to reduce stimulation of the non-target fibers. For yet another example, if side effect response metrics indicate all side effect responses are well within acceptable ranges (e.g., EMG data / measurements indicates motor response is far below the patient’s perception threshold), one or more stimulation parameters may be adjusted to increase, or up-titrate, stimulation (e.g., by increasing amplitude).

[0121] The method 600 may further include receiving metrics, or data, related to at least one stimulation response 610. Stimulation response metrics may include, for example, sensed data from the electrodes (e.g., EMG data / measurements or ECAP data / measurements, such as from the intravenous electrode 208 or electrodes of the sensors 342), sensor measurements (e.g., from the sensors 342), or patient feedback. Stimulation response data may be related to stimulation goals such as, for example, increasing cardiac pre-load, increasing volume return to the heart, decreasing splanchnic bed fluid volume, or reducing symptoms (e.g., dizziness, palpitations, increased heart rate, etc.).

[0122] In some embodiments, stimulation response metrics are used to determine whether to adjust one or more parameters 612 of the electrical stimulation delivered to the splanchnic nerve fibers. Stimulation response metrics may indicate to not adjust stimulation parameters, for example, because all stimulation responses are within an acceptable range (e.g., heart rate response to postural changes is within an acceptable range). Stimulation response metrics may indicate to adjust stimulation parameters, for example, because one or more stimulation responses are outside of an acceptable range (e.g., heart rate response to postural changes exceeds an acceptable threshold value, volume return to the heart is below an acceptable threshold value, etc.).

[0123] If stimulation response metrics indicate to adjust stimulation parameters, one or more parameters of electrical stimulation are adjusted 608. For example, if ECAPdata / measurements indicates target fibers are being stimulated below an acceptable threshold (e.g., a threshold useful to stimulate the splanchnic nerve fibers of the patient to activate splanchnic nerves innervating at least a portion of the splanchnic bed to activate constriction of splanchnic vasculature of the patient to promote volume return / cardiac preload), one or more parameters of stimulation (e.g., pulse width, amplitude, ratio of pulse width to amplitude to adjust sub-population of stimulated fibers) may be adjusted to increase, or up-titrate, stimulation of target fibers. For another example, if stimulation response metrics indicate stimulation is below a threshold effective to promote volume return / cardiac pre-load, stimulation may be increased, such as by increasing amplitude.

[0124] Although the method 600 includes both adjusting one or more parameters of stimulation in response to side effect response metrics 606 and adjusting one or more parameters of stimulation in response to stimulation response metrics 612, in some embodiments, the method 600 only includes one of adjusting one or more parameters of stimulation in response to side effect response metrics 606 and adjusting one or more parameters of stimulation in response to stimulation response metrics 612.ASPECTS

[0125] Aspect 1 is a system comprising: at least one intravenous electrode disposable within a vein of a patient to deliver electrical stimulation to splanchnic nerve fibers of the patient to activate one or more splanchnic nerves, wherein the vein is one or more of an azygos vein, a branch site of an azygos vein, a hemiazygos vein, a branch site of a hemiazygos vein, a posterior intercostal vein, and a branch site of a posterior intercostal vein; and a computing apparatus comprising at least one processor and operably coupled to the at least one intravenous electrode, the computing apparatus configured to control the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers to activate constriction of splanchnic vasculature of the patient.

[0126] Aspect 2 is an implantable medical device comprising: at least one intravenous electrode disposable within a vein of a patient to deliver electrical stimulation to splanchnic nerve fibers of the patient to activate one or more splanchnic nerves, wherein the vein is one or more of an azygos vein, a branch site ofan azygos vein, a hemiazygos vein, a branch site of a hemiazygos vein, a posterior intercostal vein, and a branch site of a posterior intercostal vein; and a computing apparatus comprising at least one processor and operably coupled to the at least one intravenous electrode, the computing apparatus configured to control the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers to activate constriction of splanchnic vasculature of the patient.

[0127] Aspect 3 is a method comprising: disposing at least one intravenous electrode within a vein of a patient and proximate to splanchnic nerve fibers of the patient to activate splanchnic nerves innervating at least a portion of the splanchnic bed of the patient, wherein the vein is one or more of an azygos vein, a branch site of an azygos vein, a hemiazygos vein, a branch site of a hemiazygos vein, a posterior intercostal vein, and a branch site of a posterior intercostal vein; and controlling electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers to activate constriction of splanchnic vasculature of the patient.

[0128] Aspect 4 is the system as in aspect 1, device as in aspect 2, or method as in any one of aspects 3, 24, and 25, wherein the at least one intravenous electrode is disposed on a lead body, and wherein the lead body optionally comprises one or more of a cuff, a stent, a balloon-expandable stent, a self-expandable stent, and a ring.

[0129] Aspect 5 is the system as in aspect 1, device as in aspect 2, or method as in any one of aspects 3, 24, and 25, wherein the at least one intravenous electrode comprises a plurality of individually controllable electrodes; and wherein controlling the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers comprises controlling each electrode of the plurality of individually controllable electrodes in response to one or more of EMG measurements, ECAP measurements, side effect response metrics, and stimulation response metrics.

[0130] Aspect 6 is the system, device, or method as in any one of aspects 1-5, 24, and 25, wherein the one or more splanchnic nerves comprises one or more of the greater splanchnic nerve, the left greater splanchnic nerve, the right greater splanchnic nerve,the lesser splanchnic nerve, the left lesser splanchnic nerve, the right lesser splanchnic nerve, the lumbar splanchnic nerve, the left lumbar splanchnic nerve, and the right lumbar splanchnic nerve.

[0131] Aspect 7 is the system, device, or method as in any one of aspects 1-6, 24, and 25, wherein the system further comprises at least one sensor, the device further comprises at least one sensor, or the method further comprises providing at least one sensor, and wherein the at least one sensor is configured to monitor at least one physiological parameter of the patient.

[0132] Aspect 8 is the system, device, or method as in any one of aspects 1-6, 24, and 25, wherein the computing apparatus is further configured to execute or the method further comprises monitoring at least one physiological parameter using at least one sensor; and wherein controlling the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers comprises controlling the electrical stimulation in response to the at least one monitored physiological parameter.

[0133] Aspect 9 is the system, device, or method as in any one of aspects 7-8, wherein the at least one sensor comprises an implantable sensor.

[0134] Aspect 10 is the system, device, or method as in any one of aspects 7-9, wherein the at least one sensor comprises the at least one intravenous electrode.

[0135] Aspect 11 is the system, device, or method as in any one of aspects 7-10, wherein the at least one sensor comprises an implantable auxiliary electrode disposable proximate the patient’s heart, and wherein the implantable auxiliary electrode disposable proximate the patient’s heart is optionally configured to monitor impedance of the inferior vena cava.

[0136] Aspect 12 is the system, device, or method as in any one of aspects 7-11, wherein the at least one sensor comprises at least one of an optical sensor configured to monitor a blood pressure of the patient and a membrane sensor configured to monitor a blood pressure of the patient.

[0137] Aspect 13 is the system, device, or method as in any one of aspects 7-12, wherein the at least one physiological parameter of the patient comprises one or more of a posture, a body position, an activity level, a heart rate, a median R-wave to R-wave timing interval, an R-wave to R-wave variability, a thoracic impedance, an abdominal impedance, a thoracic impedance, an inferior vena cava impedance, a lung impedance, a temperature, and a blood pressure.

[0138] Aspect 14 is the system, device, or method as in any one of aspects 1-13, 24, and 25, wherein the system further comprises a posture sensor, the device further comprises a posture sensor, or the method further comprises providing a posture sensor, and wherein the posture sensor is configured to monitor a posture of the patient’s body between a supine position and an upright position.

[0139] Aspect 15 is the system, device, or method as in any one of aspects 1-13, 24, and 25, wherein the computing apparatus is further configured to execute or the method further comprises monitoring a posture of the patient’s body using a posture sensor; and wherein controlling the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers comprises controlling the electrical stimulation in response to the monitored posture.

[0140] Aspect 16 is the system, device, or method as in any one of aspects 14-15, wherein monitoring the posture of the patient’s body comprises detecting a transition from a first position to a second position higher than the first position.

[0141] Aspect 17 is the system, device, or method as in any one of aspects 14-16, wherein monitoring the posture of the patient’s body comprises detecting a tilt of 60 degrees or greater, between 40 degrees and 90 degrees, or between 60 degrees and 90 degrees.

[0142] Aspect 18 is the system, device, or method as in any one of aspects 1-17, 24, and 25, wherein the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers has a pulse width of 210 mics, between 50 mics and 210 mics, or between 210 mics and 1,000 mics.

[0143] Aspect 19 is the system, device, or method as in any one of aspects 1-18, 24, and 25, wherein the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers has a frequency of 4 Hertz (Hz), 40 Hz, between 40 Hz and 60 Hz, or between 4 Hz and 100 Hz.

[0144] Aspect 20 is the system, device, or method as in any one of aspects 1-19, 24, and 25, wherein controlling the electrical stimulation delivered using the at least oneintravenous electrode to the splanchnic nerve fibers comprises delivering electrical stimulation using the at least one intravenous electrode to splanchnic nerve fibers of one or more of the L1-L4 vertebrae, the T5-T11 vertebrae, and the T10-T11 vertebrae.

[0145] Aspect 21 is the system, device, or method as in any one of aspects 1-20, 24, and 25, wherein the intravenous electrode is disposable in the vein 25 mm or less from the patient’s spinal midline, between 1 mm and 5 mm from the splanchnic nerve fibers, or 2 mm or less from the splanchnic nerve fibers.

[0146] Aspect 22 is the system, device, or method as in any one of aspects 1-21, 24, and 25, wherein controlling the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers comprises adjusting one or more parameters of the electrical stimulation, and wherein the one or more parameters optionally comprises one or more of pulse width, amplitude, frequency, on / off cycle timing, burst cycle timing, and pulse shape.

[0147] Aspect 23 is the system, device, or method as in any one of aspects 1-22, 24, and 25, wherein the at least one intravenous electrode disposable with the vein of the patient to deliver stimulation to splanchnic nerve fibers of the patient to activate one or more splanchnic nerves is configured to deliver stimulation to the splanchnic nerve fibers of the patient to activate the one or more splanchnic nerves innervating at least a portion of the splanchnic bed of the patient.

[0148] Aspect 24 is a method comprising: disposing at least one intravenous electrode within a vein of a patient and proximate to splanchnic nerve fibers of the patient, wherein the vein is one or more of an azygos vein, a branch site of an azygos vein, a hemiazygos vein, a branch site of a hemiazygos vein, a posterior intercostal vein, and a branch site of a posterior intercostal vein; and causing delivery of electrical stimulation using the at least one intravenous electrode to the splanchnic nerve fibers, the electrical stimulation configured to activate constriction of splanchnic vasculature of the patient and thereby promote volume return to the heart.

[0149] Aspect 25 is a method comprising: disposing at least one intravenous electrode within a vein of a patient and proximate to splanchnic nerve fibers of the patient, wherein the vein is one or more of an azygosvein, a branch site of an azygos vein, a hemiazygos vein, a branch site of a hemiazygos vein, a posterior intercostal vein, and a branch site of a posterior intercostal vein; and causing delivery of electrical stimulation using the at least one intravenous electrode to the splanchnic nerve fibers and thereby activating constriction of splanchnic vasculature of the patient and promoting volume return to the heart.

Claims

CLAIMSWhat is claimed:

1. A system comprising: at least one intravenous electrode disposable within a vein of a patient to deliver electrical stimulation to splanchnic nerve fibers of the patient to activate one or more splanchnic nerves, wherein the vein is one or more of an azygos vein, a branch site of an azygos vein, a hemiazygos vein, a branch site of a hemiazygos vein, a posterior intercostal vein, and a branch site of a posterior intercostal vein; and a computing apparatus comprising at least one processor and operably coupled to the at least one intravenous electrode, the computing apparatus configured to control the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers to activate constriction of splanchnic vasculature of the patient.

2. The system as in claim 1, wherein the at least one intravenous electrode is disposed on a lead body, and wherein the lead body optionally comprises one or more of a cuff, a stent, a balloon-expandable stent, a self-expandable stent, and a ring.

3. The system as in any one of claims 1 and 2, wherein the one or more splanchnic nerves comprises one or more of the greater splanchnic nerve, the left greater splanchnic nerve, the right greater splanchnic nerve, the lesser splanchnic nerve, the left lesser splanchnic nerve, the right lesser splanchnic nerve, the lumbar splanchnic nerve, the left lumbar splanchnic nerve, and the right lumbar splanchnic nerve.

4. The system as in any one of claims 1-3, wherein the computing apparatus is further configured to monitor at least one physiological parameter using at least one sensor; and wherein controlling the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers comprises controlling the electrical stimulation in response to the at least one monitored physiological parameter.

5. The system as in any one of claims 1-4, wherein the system further comprises a posture sensor configured to monitor a posture of the patient’s body between a supine position and an upright position.

6. The system as in claim 5, wherein monitoring the posture of the patient’s body comprises detecting a transition from a first position to a second position higher than the first position.

7. The system as in any one of claims 5-6, wherein controlling the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers comprises controlling the electrical stimulation in response to the monitored posture.

8. The system as in any one of claims 1-7, wherein the at least one intravenous electrode disposable with the vein of the patient to deliver stimulation to splanchnic nerve fibers of the patient to activate one or more splanchnic nerves is configured to deliver stimulation to the splanchnic nerve fibers of the patient to activate the one or more splanchnic nerves innervating at least a portion of the splanchnic bed of the patient.

9. A method comprising: disposing at least one intravenous electrode within a vein of a patient and proximate to splanchnic nerve fibers of the patient to activate splanchnic nerves innervating at least a portion of the splanchnic bed of the patient, wherein the vein is one or more of an azygos vein, a branch site of an azygos vein, a hemiazygos vein, a branch site of a hemiazygos vein, a posterior intercostal vein, and a branch site of a posterior intercostal vein; and controlling electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers to activate constriction of splanchnic vasculature of the patient.

10. The method as in claim 9, wherein the one or more splanchnic nerves comprises one or more of the greater splanchnic nerve, the left greater splanchnic nerve, the right greater splanchnic nerve, the lesser splanchnic nerve, the left lessersplanchnic nerve, the right lesser splanchnic nerve, the lumbar splanchnic nerve, the left lumbar splanchnic nerve, and the right lumbar splanchnic nerve.

11. The method as in any one of claims 9-10, wherein method further comprises monitoring at least one physiological parameter using at least one sensor; and wherein controlling the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers comprises controlling the electrical stimulation in response to the at least one monitored physiological parameter.

12. The method as in any one of claims 9-11, wherein the method further comprises providing a posture sensor configured to monitor a posture of the patient’s body between a supine position and an upright position.

13. The method as in claim 12, wherein monitoring the posture of the patient’s body comprises detecting a transition from a first position to a second position higher than the first position.

14. The method as in any one of claims 12-13, wherein controlling the electrical stimulation delivered using the at least one intravenous electrode to the splanchnic nerve fibers comprises controlling the electrical stimulation in response to the monitored posture.

15. The method as in any one of claims 9-14, wherein the at least one intravenous electrode disposable with the vein of the patient to deliver stimulation to splanchnic nerve fibers of the patient to activate one or more splanchnic nerves is configured to deliver stimulation to the splanchnic nerve fibers of the patient to activate the one or more splanchnic nerves innervating at least a portion of the splanchnic bed of the patient.

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