Determining potential influences for increasing the number of peaks within a volume pulse curve of a subject

Abstract

The invention relates to a method for determining potential influences for increasing the number of peaks within a volume pulse curve of a subject, to a method for ascertaining a pressure cuff control plan for a subject, to a device for actuating pressure cuffs provided on a subject, to the use of such a device, to a data processing device for carrying out the aforementioned method, and to a computer program product or a computer-readable medium for same.

Description

[0001] Determining ways to increase the number of peaks within a subject's volume pulse curve

[0002] TECHNICAL FIELD

[0003] The present invention relates to a method for determining and monitoring possible ways of influencing the number of peaks within a volume pulse curve of a subject (or a patient), a method for defining a pressure cuff control plan for a patient, and a device for controlling (pressure) cuffs provided (connected) to a patient for therapeutic purposes, and a device for data processing with means for carrying out these methods, and a computer program product or a computer-readable medium with instructions for a computer for carrying out these methods.

[0004] BACKGROUND OF THE INVENTION & STATE OF THE ART

[0005] So-called "endothelial flow medicine" is a novel form of physical therapy. Endothelial flow medicine can utilize various physiological effects for therapeutic purposes by modulating blood circulation. The possibilities for modulation and the underlying physiological principles are described below.

[0006] Cardiovascular diseases have long been among the most common causes of death in Europe. Atherosclerosis, which is often the underlying cause, has been a growing problem in modern civilization for decades, and medicine is attempting to address it using a wide variety of methods. Examples of atherosclerotic vascular diseases include coronary heart disease (CHD) and peripheral arterial occlusive disease (PAD), in which the arteries are narrowed or even blocked, which in advanced stages can even require amputation. Atherosclerosis can be slowed or even reversed through non-invasive treatment methods such as behavioral changes (adjusting dietary habits) and drug therapies, e.g., to lower blood pressure or cholesterol.In addition to the well-known non-invasive or drug-based therapies, invasive treatment methods are used in acute or life-threatening situations. Examples include minimally invasive vascular dilation using a balloon catheter or stent, or the removal of deposits using a special catheter, a so-called ablation catheter, which can be used to "cut out" the vessels. Surgical treatment with bypass grafting is also used as an invasive treatment method. However, all invasive procedures generally involve physical strain and risks for the patient, as well as considerable effort and expense.

[0007] In addition to the methods already mentioned, extracorporeal pulsation therapy has gained importance in recent years as a non-invasive treatment option for patients with atherosclerotic vascular diseases. Extracorporeal pulsation therapy now encompasses various procedures that utilize specialized pulsation devices. These include extracorporeal counterpulsation (ECP) or enhanced external counterpulsation (EECP), pneumatic external counterpulsation (PECP), and sequenced / sequential external counterpulsation (SECP). These procedures are applied with the appropriate medical devices.

[0008] The scientific background of the developed extracorporeal counterpulsation can be found already 20 years ago, when MH Laughlin and TN McAllister (Laughlin MH, McAllister RM. 1992 J Appl Physiol) proposed that ECP causes functional changes in the vessels through an increase in blood pressure in two types of adaptive responses: 1) structural vascular adaptation in the arterial wall and 2) altered control of vascular resistance. Structural vascular adaptation occurs through an increase in the cross-sectional area of ​​the proximal coronary arteries and is an adaptive process in which the vessel cross-section increases primarily through a thickening of the vessel wall as a result of an increase in blood pressure. However, this has the disadvantage that the very high pressure levels of EECP of up to 300 mmHg (millimeters of mercury) cause compensatory remodeling of the vessel wall with primary increase in wall thickness and not in the vessel lumen.Altered control of vascular resistance occurs through angiogenesis, which involves the growth of tiny capillaries, which, however, do not reduce but rather increase resistance in the distal circulation. In vascular occlusive disease, this often does not improve blood flow to the ischemic area. Therefore, physiologically efficient vascular remodeling involves the growth of collateral arteries and the enlargement of end arteries.

[0009] Sport and physical activity are undisputedly recognized as effective vascular training and, like the pulsation therapies described here – for example, Individual Shear Rate Therapy (ISRT - see below) (Zietzer A, Hillmeister P, Buschmann 2016, Acta Physiologica) – induce effective vascular remodeling. An important component of exercise physiology is the improvement of vascular endothelial function, which can be measured via flow-mediated dilation (FMD). Increases in FMD are considered a general improvement in vascular function, indicate an adaptive response of the vessels, and determine the so-called vascular age. An increase in FMD also enables improved regenerative vascular remodeling and increased vasodilation, thereby increasing vessel diameter.Conversely, an enlargement of the blood vessels significantly weakens the increase in shear forces, because the shear stresses caused by shear forces on the arterial wall decrease. Accordingly, the effect of any training-induced increase in blood flow is undesirably weakened, and initial training successes decrease with increasing training intensity. The training effect on the arteries can, however, be further improved under these circumstances. Tinken et al. (Tinker, Hypertension, 2010) showed that handgrip training caused a 60% increase in the shear stress rate in the brachial artery. Taylor et al. (Taylor, Ann Biomed Eng, 2002) showed that bicycle training led to a 300% increase in the shear stress rate in the supraceliacal and infrarenal aorta. Thus, the shear stress and theInfluencing these mechanisms plays a key role in the prevention of endothelial dysfunction and cardiovascular disease (Laughlin MH, Newcomer SC, Bender SB. J Appl Physiol 2008). Pulsation therapy was developed to influence this shear stress without requiring the patient to undergo active training. Its development can essentially be divided into two generations:

[0010] A "first-generation" pulsation therapy comprises the above-mentioned ECP / EECP procedures using ECP devices and serves to activate adaptive vascular remodeling. As described below, EECP, through the high pressure levels, causes compensatory remodeling of the vessel wall, with primary increase in wall thickness and angiogenesis in the capillary flow area. This leads to structural changes in the vessel wall that often do not achieve the desired effect and can, in fact, have undesirable and even harmful side effects (Soubh N, Hillmeister P, Buschmann E, Klaproth C, Buschmann I, Acta Physiologica, January 4, 2023). ECP, and especially EECP, sometimes use very high treatment pressures and are currently only indicated for the treatment of cardiac diseases and are contraindicated for the treatment of arterial circulatory disorders because they have been shown to have harmful effects in these cases (Thakkar B, Hirsch A. Vase Med. 2010).In ECP and EECP, pneumatic cuffs are forced and inflated at high pressure levels, thereby compressing soft tissue and extremities. As a result, the blood vessels within them are emptied (squeezed out), and the intravascular pressure is increased—potentially unphysiologically, with all its undesirable consequences—and additional blood volume beyond the stroke volume is mobilized, counter to the physiological flow direction.

[0011] The first generation of this type of ECP device inflates the pressure cuffs hydraulically or pneumatically, i.e. by filling or inflating the cuffs with a fluid, usually compressed air. Inflation is carried out during diastole of the cardiac cycle and is usually from distal to proximal, i.e. pressure is applied to the patient's vessels from a distant point on the treated extremity, e.g. the patient's foot or lower leg, across the distal part of the thigh proximally to the patient's buttocks. Blood flow is supported accordingly from distal to proximal. This not only causes a volume shift towards the heart, but also creates an increased venous supply in the low-pressure system to the right ventricle by squeezing the venous circulation in the legs and pelvis.However, such treatment is always directed against the direction of blood flow in a retrograde direction only during the diastolic phase. However, the resulting retrograde blood flow is increased at the expense of reduced antegrade blood flow and can trigger critical perfusion deficits in the periphery, which is particularly problematic in systemic atherosclerosis, including in the lower extremities. For this reason, first-generation retrograde pulsation therapy (ECP or EECP) is contraindicated in manifest peripheral arterial disease (PAD) (Soubh, 2023 Acta Physiologica).

[0012] The "second generation" of extracorporeal pulsation therapy (ISRT®) is not designed to increase pressure, but rather to increase intra-arterial shear stress through flow acceleration, thus stimulating arteriogenesis. Individually adjusted cuff pressures are intended to specifically influence blood flow-induced collateral vascular growth and thus stimulate arteriogenesis. The application of the second generation (ISRT®) is therefore based on influencing flow-induced collateral vascular growth and is therefore fundamentally different from first-generation extracorporeal counterpulsation therapy using ECP and EECP devices.

[0013] To successfully treat arterial circulatory disorders non-invasively, further developments of existing non-invasive procedures are necessary. Drug treatments can be associated with undesirable side effects. Therefore, there is great interest in developing highly effective, yet as side-effect-free, procedures for treating arterial circulatory disorders as possible.

[0014] In summary, there are crucial differences between the first and second generation of pulsation therapy. The first generation (EECP) is a blood pressure elevation procedure based on the misguided belief that this can increase blood flow. The second generation (ISRT, antepulsation) is a blood flow acceleration procedure in medium-sized arteries distal to a vascular occlusion. Unlike EECP, ISRT does not aim to increase blood pressure, but rather to accelerate blood flow. The underlying principle can be demonstrated by measuring blood flow in a patient's macrocirculation using ultrasound. In the resting phase, a physiologically more or less steep flow curve results, which rises simultaneously with the onset of the T wave in the ECG. With the use of ISRT, the flow curve can be modified by having a steeper rise.The ISRT procedure is designed for use in both the retrograde and antegrade directions. If blood flow is increased in the antegrade direction during ISRT, this is referred to as the antepulsation procedure. Antepulsation accelerates blood flow towards the respective extremity through the precise timing of cuff compression, which can activate the growth of collateral bypass arteries, which then develop into functional natural bypasses. See also Buschmann, IR, Lehmann, K., le Noble, F., "Physics meets molecules: Is modulation of shear stress the link to vascular prevention?" Circ. Res. 2008 Mar 14; 102(5):510-2. The antepulsation procedure increases the shear rate or the Relative Peak Shear Index (RPSI). See also Buschmann Ivo R.; Busch Hans-Jörg; Mies Günter; Hossmann Konstantin-Alexander ''Therapeutic induction of arteriogenesis in hypoperfused rat brain via granulocyte-macrophage colony-stimulating factor”, Circulation 2003; 108(5):610-5. An acceleration of blood flow velocity during ISRT in the retrograde direction serves to treat coronary artery disease (CAD), while application in the antegrade direction (here the antepulse procedure is used) serves to treat peripheral arterial occlusive disease (PAOD).

[0015] To date, only the second-generation ISRT procedure is suitable for treating patients with systemic atherosclerosis. It is important to note that with retrograde ISRT, suprasystolic therapy pressures are never achieved if PAD is present in addition to CAD. Suprasystolic therapy pressures (see first-generation devices) can lead to insufficient blood flow to peripheral vascular systems and virtually dry out these body parts. Patients with PAD should therefore not be treated with EECP (Soubh, 2023 Acta Physiologica). With ISRT, blood flow is accelerated at comparatively low, physiological therapy pressures and the maximum flow velocity is simultaneously increased. The success of the ISRT procedure is monitored using Doppler ultrasound. However, to successfully treat arterial circulatory disorders non-invasively, further developments of existing non-invasive therapy methods are necessary.Drug treatments can be associated with undesirable side effects. Therefore, there is great interest in developing highly effective, yet as side-effect-free, therapeutic methods for treating arterial circulatory disorders. Therefore, the third generation has now been developed, which utilizes various physiological effects for therapeutic purposes (endothelial flow medicine) through modulation of blood circulation. Third-generation pulsation therapy is the subject of this invention and is explained below.

[0016] While flow velocity and blood flow changes can be measured using duplex sonography during 2nd-generation ISRT / Antepuls pulsation therapy, continuous monitoring during therapy is limited due to the constantly changing probe position. Information on relative volume pulse changes, which are necessary for therapy monitoring and control, is obtained with 3rd-generation ISRT / Antepuls pulsation therapy via volume pulse measurement using plethysmography.

[0017] The third generation of pulsation therapy (ISRT / antepulsation) has another advantage over the second generation: plethysmography does not measure blood flow in the macrocirculation, but rather volume changes in the precapillary arterioles and postcapillary venules, which is important for the microcirculation. Volume increases or decreases are actually measured in the last corner, the region at risk from potential stenosis or occlusion processes of atherosclerotic occlusive disease. Optical volume pulse measurement can provide measurements that are completely different from those obtained with second-generation ultrasound. Optical volume pulse measurement is ideally suited to duplex sonography because the probes are placed behind the actual flow obstruction, allowing changes in the volume pulse in potentially critical regions to be continuously monitored and controlled.

[0018] It is an object of the present invention to provide a method for determining and monitoring possibilities for influencing the number of peaks within a volume pulse curve of a subject.

[0019] SUMMARY OF THE INVENTION

[0020] This problem is solved by the subject matter of the independent claims.

[0021] According to a first aspect of the invention, a method is provided for determining influencing options for increasing the number of peaks within a volume pulse curve of a subject (P), in particular for determining and monitoring influencing options for increasing the number of peaks within a volume pulse curve of the microcirculation beyond closed vascular sections of a patient.

[0022] In the context of this invention, "beyond" is understood to mean "behind a closed vessel section, viewed in the direction of blood flow." In the context of this document, "closed vessel section" is understood to mean a vessel section affected by vascular occlusive disease. For example, a patient may have a blockage of a major artery in the lower leg - a measurement "beyond" this blockage would then be, for example, a measurement on the big toe. This involves measuring whether, despite closed vessel sections, a relative increase in blood flow volume beyond the closed sections at the toe is achieved when steps of the method according to the invention are carried out.

[0023] The method according to the first aspect comprises the following steps, preferably in this order: a. Determining a temporal position of a cardiac cycle of the subject (P) by means of a cardiac cycle detection device, wherein a cardiac cycle corresponds to an entire diastolic and systolic phase; b. Detecting an initial volume pulse occurring in a microcirculation of the subject by means of a volume pulse detection device, in particular by means of optical plethysmography. c. Representing the volume pulse as an initial volume pulse curve and determining the number of peaks within the initial volume pulse curve; d. Controlling a pressure cuff applied to the subject during a diastole of the cardiac cycle with predetermined control parameters; e. Detecting the volume pulse occurring in the microcirculation of the subject by means of the volume pulse detection device; f.Displaying the volume pulse as a volume pulse curve and determining the number of peaks within the volume pulse curve; g. re-activating the pressure cuff during a diastole of the cardiac cycle. The re-activation of the pressure cuff can comprise a change in the control parameters to generate a modified volume pulse curve. The change in the control parameters can be selected from a group consisting of a change in a preset pressure and / or a pressure holding time of the pressure cuff, or a combination of these changes; h. detecting the modified volume pulse in the subject's microcirculation generated by the re-activation of the pressure cuff using the volume pulse detection device and displaying the volume pulse as a modified volume pulse curve; and i. determining whether there is an increase in the number of peaks within the modified volume pulse curve due to the re-activation of the pressure cuff.

[0024] According to one embodiment of the invention, the above-mentioned steps can be carried out sequentially and / or simultaneously for each pressure cuff used. In a therapy that can also be referred to as endothelial flow medicine, different modulations of the circulation (of a patient) achieve different physiological effects. Surprisingly, it has been discovered that the use of optical plethysmography can be advantageous for a method for determining and monitoring potential influences on such a therapy. Plethysmography is used to detect the volume pulse, i.e., with this technique, a volume pulse change that has a particular influence on the microcirculation can be measured (detected). Optical plethysmography uses optical sensors to detect a volume change.Typically, light is directed at the tissue of an extremity, and changes in light absorption or scattering are measured. As blood volume in the extremity's vessels increases or decreases during a cardiac cycle, the light absorption or scattering changes, which is recorded as a plethysmogram.

[0025] Furthermore, it is particularly advantageous to determine the number of volume pulse peaks and the volume pulse of diseased, underperfused vascular segments of small vessels.

[0026] In the context of this disclosure, a “volume pulse curve” is understood to mean the (graphic / optical) representation of an intravascular volume fluctuation in a patient’s blood. The volume pulse is generated by rhythmic cardiac contractions. With each compression, the heart generates cyclical pressure fluctuations through volume shifts to the periphery, which exert a modulating function on the arterial blood vessels. Due to the inertia of the incompressible blood column, a local intravascular pressure increase occurs in the arteries after each cardiac muscle contraction. The viscoelastic properties of the arteries, coupled with the increase in transmural pressure, cause the vessel wall to stretch, resulting in a local cross-sectional expansion. The stroke volume ejected by the heart is temporarily stored in the blood vessel and only after a time delay is it pushed distally against the closed aortic valve; this is known as the “stroke volume curve.”Windkessel effect: The ability of elastic arteries and the aorta to expand after a cardiac contraction, thus converting part of the kinetic energy of the outflowing blood into potential energy. The damping property of the arterial vascular system converts pressure fluctuations into a continuous (longitudinal) blood flow. The pressure gradient that has developed between the dilated and the following arterial segment is the driving force for the acceleration and forward propulsion of the stroke volume stored in the vessel lumen. Storage, emptying, and continued flow are simultaneous phenomena that are captured in the volume-pulse curve—determined by duplex sonography or plethysmography.

[0027] The volume pulse curve, unlike the leading pressure wave, is understood as a wave-like movement of the arterial wall due to expansion and subsequent contraction as blood moves from the heart to the body's periphery. Different measurement methods can be used to represent the volume pulse curve differently, each capturing different physical properties (pressure, acceleration / velocity, volume).

[0028] A volume pulse curve therefore contains three basic phenomena: pressure pulse, flow pulse (blood flow velocity), and volume pulse. In a system in which the volume pulse curve runs in only one direction, the three basic phenomena of the volume pulse curve exhibit temporally consistent curve progressions. All volume pulse curves (pressure, flow, volume) always run synchronously and simultaneously and can be described as follows:

[0029] The pressure wave mentioned above can be represented as a pressure curve, which should not be confused with blood flow. A pressure pulse curve can be recorded, for example, using pressure sensors in appropriate pneumatic cuffs. The pulse wave velocity indicates the time it takes for cyclical pressure fluctuations to propagate through the vascular system and spread as a pressure pulse wave. The stiffer a vessel, the faster the pressure wave propagates centrifugally in the longitudinal direction. Blood pressure-induced deflections of the vessel walls can be recorded using sensors in pneumatic cuffs. The pulse wave velocity describes the propagation speed of the pressure wave along the arteries in m / s.For the purposes of this document, the term "optical plethysmography" refers to a measurement method used to assess arterial vascular disease by applying a probe of a detection device to, for example, fingers and toes. Optical plethysmography measures the relative number of blood particles and thus indirectly, based on the volume-pulse curve, relative volume changes. Pressure waves and volume waves are images of a wave propagating longitudinally, synchronously with the pulse. They are related but measured differently. However, the pulse pressure waves and flow waves are not synonymous with the blood volume wave. The volume wave is a movement of blood caused by systolic compression as the heartbeat volume, which is pumped to the periphery.

[0030] In this document, the term “peak” refers to abrupt changes in the volume pulse curve in the sense of an increase or decrease in intravascular volume.

[0031] The volume pulse curve indicates the change in filling volume and allows indirect conclusions to be drawn about the flow behavior. The relative change in the velocity of particles can be recorded using reflected sound or light waves. Using pulsed Doppler, which provides information about the depth of the blood vessel or the distance to the diverted particles, their velocity can be calculated (exactly). In the above-mentioned second generation of pulsation therapy, flow accelerations (and changes in direction) are determined using ultrasound measurements in the macrocirculation (RPS l method). A so-called Doppler shift provides information about the velocity and flow direction. The ultrasound measurement produces a curve in which the amplitude indicates the velocity and the area under the curve indicates the volume of blood moved. Changes in blood flow can be determined using ultrasound measurements.However, this can only be assessed in larger blood vessels that can be imaged sonographically and only to a very limited extent during therapy. If the diameter of the vessel in question is known, the volume pulse per unit time in the relevant vessel section can be calculated based on the central flow velocity. The flow velocity of blood in closed vessels depends on the prevailing resistance, pressure gradient and vessel diameter, as well as the viscosity. In a closed blood system, the blood expands discontinuously and only reaches the peak flow velocity determined by duplex sonography for a short time, before being slowed down to practically zero due to peripheral capillary resistance. Reflected waves can even lead to brief retrograde blood flow with a dicrotic wave; in vessels distant from the heart, dicrotia or dicrotic wave refers to the second peak of an arterial blood pressure curve.The flow velocity in the arterial system is comparable to the slow-moving traffic on a congested highway. Behind obstructions in the flow path, a drop in pressure occurs downstream due to the inertia of the flowing fluid. For this reason, the low-pressure venous system is less prone to discontinuous flow fluctuations.

[0032] In the context of this document, the term “volume pulse curve” can be understood in particular to mean that each heartbeat of a patient moves the stroke volume, which can be recorded as a volume pulse in the entire blood vessel system.

[0033] Blood flow follows the pressure wave emanating from the heartbeat. Changes in the volume pulse curve can be displayed graphically and are similar to the blood flow curve or pressure pulse curve. The volume pulse curve can be measured as an increase in volume using optical plethysmography in the arterial and venous vessels, e.g., on the fingertip or toe. Optical plethysmography does not measure the pulse by measuring pressure, but rather by measuring volume changes using infrared light over the vessel sections, e.g., on a patient's toe or finger. The volume pulse can be recorded using optical plethysmography in the sum of the smallest blood vessels in the microcirculation. The amount of absorbed and not reflected infrared light correlates with volume fluctuations in the blood volume in the tissue section under investigation. These changes are not directly dependent on blood pressure or flow velocity, but rather depend on volume shifts.

[0034] If the vessel cross-section or fill volume remains constant, when inflow and outflow are in balance, blood flow cannot be measured using a volume pulse curve. Only when the volume fill levels in the vessel sections change can we obtain information about the volume changes in the measured tissue section through optical plethysmography. Because fluids are incompressible, the vessel cross-section corresponds to the respective fill volume. With its fluctuations, this volume synchronously reflects the waves of the pressure pulse and flow pulse. This allows changes in volume fill to be continuously recorded, particularly in sections that receive little perfusion due to flow obstructions, or in smaller vessels that cannot be demarcated sonographically. The larger the area under the derived curve, the greater the volume moved.

[0035] At its lowest and highest point, the volume pulse curve exhibits reversal points (similar to the ebb and flow of the tides) for the ascending and descending parts, respectively. The area under the curve corresponds to the total relative volume of blood moved. The steepness of the curve provides information about the relative acceleration, while the amplitude provides information about the relative speed, but not about the absolute speed (Vmax). It also provides no information about the direction of flow. At a constant flow velocity, when inflow and outflow are throttled and not pulsatile - i.e. occur at the same speed - the volume pulse curve exhibits no change, because no volume fluctuations occur within the vascular section.

[0036] For the purposes of this document, the term "microcirculation" refers to the part of the bloodstream that occurs in the smallest blood vessels, e.g., arterioles, venules; pre- and post-capillary. Accordingly, a patient's microcirculation blood vessel is understood to be a vessel in the sense of arterial blood capillaries or arterioles. Both the patient's initial volume pulse wave profile and the altered volume pulse wave profile are preferably recorded using measurements in or at the same part of the patient.

[0037] Basic measurable parameters of circulation include pressure, flow (acceleration and velocity), and changes in the vascular system's level (the volume pulse). Each individual parameter requires a specific measurement method. Due to the pulsatile nature of blood flow, each parameter can be displayed and monitored as a time-dependent, pulse-synchronous waveform. All pulse curves (pressure, flow, volume) can be recorded at any point in the vascular system and display a waveform synchronized with the heartbeat.

[0038] According to a second aspect of the invention, a method is provided for establishing a pressure cuff activation plan for a subject, wherein, based on the method for determining influencing options for increasing the number of peaks within a volume pulse curve of a subject, a schedule for pressure cuff activation is established as a function of an upper transition point of an R-wave of a cardiac cycle of the subject, and the time of the upper transition point of the R-wave is used as the temporal zero point for the subsequent step of reactivating the pressure cuffs in order to set the reactivation of the pressure cuffs to a period during a diastole immediately following the R-wave.

[0039] According to a further aspect of the invention, a device for controlling pressure cuffs provided on a subject is provided, comprising a plurality of independently controllable pressure cuffs; a cardiac cycle detection device for determining the temporal position of a cardiac cycle, in particular an electrocardiogram (ECG) device, further in particular a 3-channel ECG recording device; a volume pulse detection device for detecting volume pulses in the microcirculation of the subject (P) and displaying the volume pulse as a volume pulse curve, preferably in the form of an optical plethysmography sensor; and a control unit for controlling the pressure cuffs. The control unit is designed to control the pressure cuffs during a diastole of the determined cardiac cycle according to a pressure cuff control plan defined using the method according to an embodiment of the invention.

[0040] According to a further aspect of the invention, the use of the device according to the preceding aspect for carrying out a process defined by the method according to an embodiment of the invention

[0041] Pressure cuff control plan provided.

[0042] According to a further aspect of the invention, the methods according to the invention are computer-implemented methods.

[0043] According to a further aspect, a device for data processing is provided, comprising means for carrying out the method according to an embodiment of this invention, in the event that this is a computer-implemented method: The device can be used to acquire and process simultaneously acquired measured values ​​with computer-aided analysis for carrying out therapeutic methods of endothelial flow medicine.

[0044] According to a further aspect, a computer program product or computer-readable medium is provided, comprising instructions which, when executed by a computer, cause the computer to carry out at least one of the methods described above, in the event that the method is a computer-implemented method.

[0045] Features that were previously described for one of the methods according to the invention can also be used analogously to define the other method according to the invention, to define the device according to the invention, to define the use according to the invention, to define the device for data processing according to the invention, to define the computer program product according to the invention and / or to define the computer-readable medium according to the invention and are hereby expressly disclosed as corresponding device features.The same applies in the other direction: Features disclosed only for defining the device according to the invention, for defining the use according to the invention, for defining the data processing apparatus according to the invention, for defining the computer program product according to the invention, and / or for defining the computer-readable medium according to the invention can also be used to define one or both of the methods according to the invention. As used here and also in the appended claims, the singular forms "a" and "the" can also include their plurals, unless the context clearly indicates otherwise. Similarly, the words "comprise," "contain," and "comprise" are to be understood as both "exclusive" and "non-exclusive," i.e., in the sense of "including, but not limited to...".The terms "several", "multiple" or "plurality" usually refer to two or more, i.e. 2 or >2, including further integer multiples of 1, whereas the terms "single" or "alone" refer to one (1), i.e. "=1". Furthermore, the expression "at least one" or "at least one" is to be understood as one or more, i.e. 1 or >1, also including integer multiples. Furthermore, the words "herein", "above", "previously" and "below" or "subsequently" and words of similar meaning, when used in this description, are intended to refer to this description as a whole and not to specific parts of the description.

[0046] The description of specific embodiments in this specification is not intended to be exhaustive, nor is the disclosure provided herein intended to be limited to the precise form disclosed. While specific embodiments and examples described herein are illustrative of the disclosure, various equivalent modifications are possible within the scope of the disclosure, as would be appreciated by one skilled in the art. Specific technical elements of described embodiments may be combined with or substituted for technical elements in other embodiments. In the drawings, like reference numerals designate like elements to avoid repetition, and parts that one skilled in the art can implement without special knowledge may be omitted for clarity.

[0047] Additional embodiments of the individual aspects are described below.

[0048] According to one embodiment, the method for determining possible ways of influencing the increase in the number of peaks within a volume pulse curve of a subject further comprises, preferably after the step of determining whether there is an increase in the number of peaks within the changed volume pulse curve due to the renewed activation of the pressure cuff: a. Activating the pressure cuff and at least one further pressure cuff applied to the subject, b. Detecting the volume pulse occurring in the microcirculation of the subject by means of the volume pulse detection device, c. Representing the volume pulse as a volume pulse curve and determining the number of peaks within the volume pulse curve; d.Reactivating the pressure cuff and the at least one additional pressure cuff during a diastole of the cardiac cycle, wherein reactivating the pressure cuff and the at least one additional pressure cuff comprises changing the activation parameters to generate a modified volume pulse curve. The change in the activation parameters can be selected from a group consisting of changing a preset pressure and / or a pressure holding time of the pressure cuff, changing a sequence of pressure applications by the pressure cuffs, changing a time interval between pressure applications by the pressure cuffs, or a combination of these changes. e.Detecting the altered volume pulse in the subject's microcirculation generated by the renewed activation of the pressure cuffs using the volume pulse detection device and displaying the volume pulse as an altered volume pulse curve; and f. Determining whether there is an increase in the number of peaks within the altered volume pulse curve due to the renewed activation of the pressure cuffs.

[0049] Reactivating one or more pressure cuffs has the advantage that an increase in the number of peaks within the altered volume pulse curve can be achieved more quickly and the effect of the peak increase is validated. According to one embodiment of the method for determining possible ways of influencing an increase in the number of peaks within a volume pulse curve of a subject, the steps of reactivating the pressure cuffs, detecting the altered volume pulse, and determining whether the reactivation of the pressure cuffs results in an increase in the number of peaks within the volume pulse curve are repeated until the number of peaks within the altered volume pulse curve determined in the last step corresponds to at least two peaks, preferably three peaks or more. This has the advantage that the frequency of flow-induced endothelial activation per cardiac cycle is increased.The procedure is designed to maximize the effect of endothelial flow medicine on the microcirculation in order to achieve the strongest possible therapeutic effect.

[0050] According to a further embodiment of the method for determining influencing options for increasing the number of peaks within a volume pulse curve of a subject, the step of reactivating the pressure cuffs is preceded by a step of determining the time of an upper transition point of an R-wave of a cardiac cycle of the subject, wherein the time of the upper transition point of the R-wave is used as a temporal zero point for triggering the subsequent step of reactivating the pressure cuffs in order to specify the reactivation of the pressure cuffs for a period during a diastole immediately following the R-wave. This has the advantage that the compression of time-controlled cuffs activates the Windkessel effect described above to increase the number of peaks.The blood volume displaced by the compressed cuff is thus temporarily stored in the subsequent blood vessels according to the windkessel effect and is only pushed forward by the selected time delay.

[0051] According to one embodiment of the method for determining possible ways to increase the number of peaks within a volume pulse curve of a subject, a sequence of pressure applications by the pressure cuff(s) comprises controlling at least one distal pressure cuff arranged on an extremity of the subject. Subsequently, the control of at least one proximal pressure cuff arranged on the same extremity of the subject can occur, or at least one proximal pressure cuff arranged on an extremity of the subject can be controlled, followed by the control of at least one distal pressure cuff arranged on the same extremity of the subject.Furthermore, optionally additionally, a change in the time interval between the pressure applications by the pressure cuffs can comprise a temporal overlap of the activation of at least one distal pressure cuff arranged on an extremity of the subject and a temporal overlap of the activation of at least one proximal pressure cuff arranged on the same extremity of the subject, preferably wherein the change in the time interval between the pressure applications by the pressure cuffs comprises a temporal overlap of the pressure holding times of at least two pressure cuffs. This has the advantage that the movement of the blood volume into the target area to be treated can be controlled by the successive compressions of cuffs. The aim of this method and technique is to treat different vascular flow areas, and this goal can be controlled by this measure.Here is an example: Firstly, the compression of one cuff, e.g. a hip cuff, moves the blood towards the heart, but also towards the foot. If you want to treat patients with peripheral arterial disease (PAD) and ischemic tissue in the lower leg or foot, the blood volume can be accelerated further towards the lower leg by compressing a second distal thigh cuff. If the compression of the hip cuff overlaps with the compression of the thigh cuff, the blood in the area of ​​the thigh cuff can no longer escape proximal to the hip and the blood volume is moved entirely towards the foot. The blood volume movement towards the foot is thereby maximized. By increasing the moved blood volume, the number of peaks within a subject's volume pulse curve can also be efficiently increased.

[0052] According to one embodiment of the method for determining possible influences to increase the number of peaks within a subject's volume pulse curve, a peak represents an abrupt increase in the pressure of the volume pulse curve or an abrupt decrease in the pressure of the volume pulse curve, and / or both the subject's initial volume pulse curve and the subject's altered volume pulse curve are based on volume flows recorded by the volume pulse recording device in the microcirculation area to be examined, or "microcirculation" for short, of the subject. This has the advantage that the effects in the microcirculation area to be treated are recorded locally—that is, where the endothelial flow activation also exerts its effect. We therefore record either cranial, caudal, and also local influence effects in the microcirculation and can thus derive an individual therapy effect for this region.Possible therapeutic effects no longer have to be derived approximately from ultrasound measurements for the terminal flow area, as is the case with the 2nd generation of pulsation therapy.

[0053] According to one embodiment, the method for determining possible ways to increase the number of peaks within a volume pulse curve of a subject further comprises a step of determining an enlargement of the subject's vascular endothelial cells due to the increase in the number of peaks. This has the advantage of being able to measure how the vascular resistance in the microcirculation decreases. Along with arteriogenesis, the reduction in resistance in the microcirculation is the most important therapeutic effect of pulsation therapy for improving blood perfusion in cardiovascular occlusive diseases.

[0054] According to one embodiment of the method for determining a pressure cuff control plan for a subject, the pressure to be applied to the subject's extremity by the pressure cuffs is in a range of 80 mmHg to 180 mmHg, preferably with an accuracy of ± 15 mmHg. This has the advantage that the therapy can be precisely individualized. Previous devices exhibited a pressure fluctuation of > 40 mmHg during cuff compression. Individual therapy pressures (ISRT) range between 80 mmHg and 180 mmHg, thus sometimes even subsystolic and serve to achieve the most effective therapy outcome. Pressure levels that are too low or too high can lose the therapeutic effect, and the pressure levels must therefore be selected as precisely as possible.

[0055] According to one embodiment of the method for determining a pressure cuff control plan for a subject, in order to determine the pressure cuff control plan of the subject, in addition to the control of the pressure cuffs due to the change in the control parameters leading to an increase in the peak frequency, a control of a further pressure cuff is used as a basis, wherein the pressure cuff and / or the at least one further pressure cuff is arranged on an extremity of the subject and wherein the further pressure cuff is arranged on the extremity of the subject at a location that is more distal than the previously used pressure cuffs, wherein preferably only the further pressure cuff is controlled exclusively during a period in which the control of the previously used pressure cuffs is paused,Furthermore, the additional pressure cuff is preferably controlled exclusively during the period in which the control of the previously used pressure cuffs is paused, with a low pressure below 80 mmHg, preferably 60 mmHg, for a fixed period (te), which lasts over several cardiac cycles. This has the advantage that in the regions to be treated (e.g., the lower leg region), the blood volume and also the lymph are squeezed out once with the compression of a cuff at a low pressure level. This process can last up to 10 seconds, and pulsation therapy is paused during this period. The control of this method serves to ensure that, by squeezing out any accumulated blood volume, the pressure gradient is maximally increased again during a possible subsequent cuff compression as part of the standard pulsation therapy.

[0056] BRIEF DESCRIPTION OF THE DRAWINGS

[0057] They show:

[0058] Figure 1 shows a method according to an embodiment of the invention;

[0059] Figures 2a-2c show a temporal relationship between the electrocardiogram of a patient shown in Figure 2a and the R-wave occurring therein, the pulse wave in the patient's aorta following the pre-ejection period "PEP" shown in Figure 2b, and the pulse wave in a peripheral artery of the patient shown in Figure 2c. Figure 3 Changes in the volume pulse curves; representation of a

[0060] Volume pulse curve and the increase of volume peaks by means of peak frequency increase.

[0061] Figure 4a-4c shows the different ways of attaching pressure cuffs

[0062] Figure 5 shows the hemodynamic changes during

[0063] Pulsation therapy; a simplified diagram of the arterial, capillary and venous vascular system; and

[0064] Figures 6a-6f show the control and positioning of the pressure cuffs depending on the indication.

[0065] DETAILED DESCRIPTION

[0066] In the following description of the present invention using an exemplary embodiment, the figures represent the subject matter of the invention only schematically. The exemplary embodiment is illustrated in the figures and is described in more detail below.

[0067] The method for determining possible ways to increase the number of peaks within a volume pulse curve of a subject P, according to one exemplary embodiment, begins with step S01 and is illustrated in Figure 1. In step S01, a temporal position of a cardiac cycle of the subject P is determined by a cardiac cycle detection device, wherein a cardiac cycle corresponds to an entire diastolic and systolic phase; in step S02, an initial volume pulse occurring in a microcirculation of the subject P is then detected by a volume pulse detection device, in particular by optical plethysmography. Step S03 represents the volume pulse as an initial volume pulse curve and determines the number of peaks within the initial volume pulse curve.According to the exemplary embodiment, this is followed by controlling S04 a pressure cuff D1 applied to the subject P during a diastole of the cardiac cycle with predetermined control parameters. In the next step, the volume pulse occurring in the microcirculation of the subject P is detected S05 by means of the volume pulse detection device, the volume pulse is displayed as a volume pulse curve, and the number of peaks within the volume pulse curve is determined S06.According to the exemplary embodiment, this is followed by renewed activation S07 of the pressure cuff D1 during a diastole of the cardiac cycle, wherein the renewed activation S07 of the pressure cuff D1 comprises a change in the activation parameters to generate a modified volume pulse curve, and wherein the change in the activation parameters is selected from a group consisting of a change in a preset pressure and / or a pressure holding time t2 of the pressure cuff D1, or a combination of these changes. Step S08 comprises detecting S08 the modified volume pulse in the microcirculation of the subject P generated by the renewed activation S07 of the pressure cuff D1 by the volume pulse detection device and displaying the volume pulse as a modified volume pulse curve.Finally, in step S09, a determination is made as to whether there is an increase in the number of peaks within the changed volume pulse curve due to the renewed control S07 of the pressure cuff D1.

[0068] In addition, according to another embodiment, the method can comprise further steps. Step S10 involves activating the pressure cuff D1 and at least one further pressure cuff D2 applied to the subject. Step S11 involves detecting the volume pulse occurring in the microcirculation of the subject P using the volume pulse detection device. Step S12 involves displaying the volume pulse as a volume pulse curve and determining the number of peaks within the volume pulse curve.According to step S13, the pressure cuff D1 and the at least one further pressure cuff D2 can be activated again during a diastole of the cardiac cycle, wherein the activated again S13 of the pressure cuff D1 and the at least one further pressure cuff D2 comprises a change in the activation parameters to generate a changed volume pulse curve, and wherein the change in the activation parameters is selected from a group consisting of a change in a preset pressure and / or a pressure holding time t2, t4 of the pressure cuff D1, a change in a sequence of pressure applications by the pressure cuffs D1, D2, a change in a time interval ts between the pressure applications by the pressure cuffs D1, D2, or a combination of these changes.This can be followed by step S14, namely detecting the changed volume pulse in the microcirculation of the subject P generated by the renewed actuation S13 of the pressure cuffs D1, D2 by the volume pulse detection device and displaying the volume pulse as a changed volume pulse curve; and determining S15 whether there is an increase in the number of peaks within the changed volume pulse curve due to the renewed actuation S13 of the pressure cuffs D1, D2. According to one embodiment, the method for determining influencing options for increasing the number of peaks within a volume pulse curve of a subject P further comprises a step S16 of determining an enlargement of vascular endothelial cells of the subject P due to the increase in the number of peaks.

[0069] According to one embodiment of the invention, the above steps may be performed sequentially and / or simultaneously for each pressure cuff used.

[0070] In optical plethysmography, the volume change is measured in the periphery. The pulse wave depicted in Figure 2 can be visualized as a volume change using optical plethysmography, as shown in Figure 3. Typically, a volume peak is observed per cardiac cycle, indicated by arrows in Figures 3a-c. The key to this invention is to increase the number of wave peaks per cardiac cycle. These volume peaks induce endothelial remodeling.

[0071] Figures 2a-2c show a temporal relationship between the electrocardiogram of a patient shown in Figure 2a and the R-wave occurring therein, the pulse wave in the patient's aorta following the pre-ejection period (PEP) shown in Figure 2b, and the pulse wave in a peripheral artery of the patient shown in Figure 2c. The Pulse Wave Transit Time (PWTT) refers to the time it takes for a pulse wave to move from a specific point in the cardiovascular system, e.g. from the heart, to another point, e.g. to a specific section of a vessel. The further away a vessel is, the longer the PWTT. The pulse wave and the volume pulse curve are two different phenomena that are simultaneously related. The volume pulse wave can be measured as a function of the heart's action, similar to a pulse pressure wave. The plethysmography described above is used for this purpose.

[0072] Figure 3a shows a typical volume pulse curve of individual cardiac actions running one after the other. Figure 3b shows volume pulse curves from successive cardiac actions with subsequent cuff inflation (control of the pressure cuff) at the same wavelength. Figure 3c shows a volume pulse curve from successive cardiac actions with two subsequent cuff inflations of the same wavelength. Figures 3b and 3c show how the volume pulse curves appear per cardiac cycle during pulsation therapy with a device according to the invention. During pulsation therapy, one volume pulse peak per cardiac cycle is observed for each cuff. A volume pulse curve is created by the cardiac contraction, and the next volume pulse peak is created by the respective cuff inflation. With an additional volume pulse due to cuff inflation, the inflowing and outflowing volumes are the same. As the number of cuffs used increases, the amplitude increases.Additional volume pulse peaks occur. The zero line shifts because the areas above and below the zero line are the same size, but the overall amount of volume moved increases.

[0073] The inventive method of endothelial flow medicine can also be referred to as a “pulse-wave enhancement” (PWE) method or peak frequency enhancement (PFE) method or also as an “intravascular machine gun effect” method or IVMAGE method, which serves in particular to stimulate endothelial function and especially endothelial vascular remodeling.

[0074] In peripheral vascular regions, a delayed second, smaller wave (shown as a small peak in the volume pulse curve) may occur after the first main wave as a result of the Windkessel effect (Figure 3b). If two volume peaks already occur per cardiac cycle under physiological conditions, the number of volume peaks should be increased from two to at least three or four. A device according to the invention that implements the PWE technique (and is commercially available, e.g., a so-calledThe device (e.g., the “Marathor®” device) can comprise several independently controllable, differently shaped pressure cuffs, a cardiac cycle detection device for determining the temporal position of a cardiac cycle, preferably in the form of a 3-lead ECG lead device with the option of temporal recording, a pulse wave detection device for detecting a pulse wave profile of the patient, preferably in the form of a pulse oscillography sensor, and a control unit for controlling the pressure cuffs. The control unit is designed so that the pressure cuffs are controlled during diastole according to a pressure cuff control plan, which was determined by the method described above. The optical pulse oscillography device for recording the patient's pulse wave profile is an integral part of the device according to the invention and can be in the form of an infrared sensor on the tips of fingers or toes orother easily accessible peripheral sections.

[0075] The components of the device described above are used to determine the pressure cuff control plan and to monitor the therapy.

[0076] The aim is to increase the stimulation of the endothelium of the examined microcirculation using PWE methods. Examples are given in Figures 3a-b. By using pulsation therapy with a device according to the invention, the cuff and pressure configuration can be selected to increase the number of peaks. In Figure 3b, the first peak is generated by cardiac contraction or by activation (inflation) of the first proximal cuff, but can also generate the second peak. A third or fourth peak can be induced by additional cuffs or by the Windkessel effect. An increase in the number of volume pulse peaks is achieved through correct cuff inflation in the flow area of ​​the examined vessels.This increase can be influenced both by interference from reflected waves and directly by cuff inflation. The ECG records the excitation and propagation of an electrical signal leading to muscle contraction. The systolic contraction of the ventricle is initiated by a high R-wave (see Figure 2). The cardiac contraction results in a pressure wave, the volume pulse curve, which leads to a delayed expansion of the aorta.

[0077] As shown in Figure 2b, PEP refers to the pre-ejection period, i.e., the period just before blood is pumped into the aorta. Figure 2c also shows PWTT. As shown, PWTT includes both PEP and a-PWTT. A-PWTT describes the time it takes for the volume pulse curve to travel from the heart to the measurement point.

[0078] Changes in vessel cross-section, wall thickness, wall elasticity, or vessel branching cause changes in resistance (impedance). When waves encounter a change in impedance, reflection occurs, leading to interference with the superposition of the back-and-forth transverse mechanical waves.

[0079] Figure 5 shows a simplified diagram of the arterial, capillary, and venous vascular system. Optical plethysmography can only detect a volume change if the inflow is faster or slower than the outflow. This must be taken into account when interpreting the volume-pulse curve when pneumatic cuffs are applied, for example, for occlusion pressure measurements or during antepulsation therapy. In the simplified diagram, the space between the legs of both triangles represents the arterial, capillary, and venous vascular system: on the left is the artery, the arrow pointing from left to right represents the capillary flow area, and on the right is the venous outflow.

[0080] Figures 6a-6f show a representation of the control and positioning of the pressure cuffs depending on the indication (peripheral arterial occlusive disease “PAOD”), “Cardiology I (cardiological indication - e.g. angina pectoris, treatment of cardiac arteries)”, Cerebral I (cerebral indication - e.g. vascular dementia, post-stroke, Raynaud's, renal / erectile dysfunction, Cerebral II, hypertension). In the exemplary arrangement shown in Figure 6c, the dotted pressure cuff is a hip pressure cuff or hip cuff arranged proximally on the patient's hip, the pressure cuff shown in diagonal hatching (from bottom left to top right) is a thigh pressure cuff or thigh cuff arranged on the patient's left thigh, and the pressure cuff shown in crossed hatching is a lower leg pressure cuff or lower leg cuff or calf cuff arranged distally on the patient's left lower leg.The selection of the appropriate cuff size can be crucial for the success of the method according to the invention, whereby the cuff size must be determined separately for each pressure application area. The cuff size is selected based on the circumference of the extremity, which is measured at a suitable location. Furthermore, a cardiac cycle detection device in the form of a 3-channel ECG recording device is connected to the patient P as a component of the device according to the invention for controlling the pressure cuffs in order to record a corresponding ECG signal. Furthermore, a volume pulse curve detection device in the form of an optical plethysmography sensor is connected to the patient P as a component of the device according to the invention for controlling the pressure cuffs in order to be able to continuously record a volume pulse curve profile occurring in a microcirculatory blood vessel of the patient P.

[0081] Figure 6a shows a configuration for determining options for increasing the number of peaks within a volume pulse curve of a subject in the indication "peripheral arterial occlusive disease," with the inflation order as follows: 1. cuff shown in dotted lines; latency 100 msec (milliseconds); 2. cuffs shown in diagonal hatching (from bottom left to top right).

[0082] Figure 6b shows a configuration for determining possible influences to increase the number of peaks within a volume pulse curve of a subject for the indication "Cardiology I", where the inflation order is as follows: cuff shown in dotted lines and cuffs shown in crossed hatching simultaneously, as well as for the indication Cerebral I, where the inflation order is as follows: 1. cuff shown in dotted lines; latency 100 msec; 2. cuffs shown in crossed hatching. Figure 6c shows a configuration for determining possible influences to increase the number of peaks within a volume pulse curve of a subject for the indication Cardiology II (ECP concept), where the order is: 1. cuffs shown in crossed hatching; latency 100 msec; 2. cuffs shown in diagonal hatching (from bottom left to top right); latency 100 msec; 3. cuffs shown in dotted lines.

[0083] Figure 6d shows a configuration for determining manipulation options to increase the number of peaks within a volume pulse curve of a subject in the indication Raynaud's syndrome, where the order of inflation is as follows: 1. cuffs shown in crossed hatching; latency 100 msec; 2. cuffs shown in diagonal hatching (from top left to bottom right).

[0084] Figure 6e shows a configuration for determining manipulation options for increasing the number of peaks within a volume pulse curve of a subject in the indication Renal / Erectile Dysfunction, where the order of inflation is as follows: 1. shown in crossed hatching; latency 100 msec; 2. shown in diagonal hatching (from bottom left to top right); as well as for the indication Cerebral II where the order of inflation is as follows: 1. shown in diagonal hatching (from bottom left to top right); latency 100 msec; 2. shown in crossed hatching.

[0085] Figure 6f shows a configuration for determining possible manipulations to increase the number of peaks within a volume pulse curve of a subject in the indication of hypertension, where the order of inflation is as follows: 1. cuffs shown in diagonal hatching (from bottom left to top right); latency 100 msec; 2. cuffs shown in crossed hatching; latency 100 msec; 3. cuffs shown in diagonal hatching (from top left to bottom right).

[0086] In other words, the controllable pressure cuffs D1, D2, etc. can be attached to the patient P according to one embodiment, on at least one of: the hip, an extremity and its acral region, in particular an arm, further in particular an upper arm, a forearm, or a leg, in particular a thigh or a lower leg, or a torso region. According to a further embodiment, the control of a pressure cuff can occur in a pressure range of the mean arterial blood pressure, in particular with a time offset of, for example, 240 msec after the measured R-wave. Both the pressure range and the time offset can be changed.

[0087] While an embodiment of the present invention has been described above, the present invention is not limited to the above-described embodiment. Various modifications in design may be made without departing from the invention, as defined by the following claims.

Claims

CLAIMS 1 . A method for determining possible ways of increasing the number of peaks within a volume pulse curve of a subject (P), the method comprising the following steps, preferably in this order: Determining (S01) a temporal position of a cardiac cycle of the subject (P) by a cardiac cycle detection device, wherein a cardiac cycle corresponds to an entire diastolic and systolic phase; Detecting (S02) an initial volume pulse occurring in a microcirculation of the subject (P) by means of a volume pulse detection device, in particular by means of optical plethysmography, Representing the volume pulse as an initial volume pulse curve and determining (S03) the number of peaks within the initial volume pulse curve; Controlling (S04) a pressure cuff (D1) applied to the subject (P) during a diastole of the cardiac cycle with predetermined control parameters; Detecting (S05) the volume pulse occurring in the microcirculation of the subject (P) by means of the volume pulse detection device, Representing the volume pulse as a volume pulse curve and determining (S06) the number of peaks within the volume pulse curve; re-activating (S07) the pressure cuff (D1) during a diastole of the cardiac cycle, wherein the re-activation (S07) of the pressure cuff (D1) comprises a change in the activation parameters to generate a changed volume pulse curve, and wherein the change in the activation parameters is selected from a group consisting of a change in a preset pressure and / or a pressure holding time (t2) of the pressure cuff (D1), or a combination of these changes; Detecting (S08) the changed volume pulse in the microcirculation of the subject (P) generated by the renewed activation (S07) of the pressure cuff (D1) by the volume pulse detection device and displaying the volume pulse as a changed volume pulse curve; and Determining (S09) whether there is an increase in the number of peaks within the changed volume pulse curve due to the renewed control (S07) of the pressure cuff (D1).

2. Method for determining possibilities for influencing the number of peaks within a volume pulse curve of a subject (P) according to claim 1 , wherein the method further comprises, preferably after step (S09), Controlling (S10) the pressure cuff (D1) and at least one further pressure cuff (D2) applied to the subject, Detecting (S11) the volume pulse occurring in the microcirculation of the subject (P) by means of the volume pulse detection device, Representing the volume pulse as a volume pulse curve and determining (S12) the number of peaks within the volume pulse curve; re-activating (S13) the pressure cuff (D1) and the at least one further pressure cuff (D2) during a diastole of the cardiac cycle, wherein the re-activation (S13) of the pressure cuff (D1) and the at least one further pressure cuff (D2) comprises a change in the activation parameters to generate a changed volume pulse curve, and wherein the change in the activation parameters is selected from a group consisting of a change in a preset pressure and / or a pressure holding time (t2, t4) of the pressure cuff (D1), a change in the sequence of pressure applications by the pressure cuffs (D1, D2), a change in a time interval (ts) between the pressure applications by the pressure cuffs (D1, D2), or a combination of these changes; Detecting (S14) the changed volume pulse in the microcirculation of the subject (P) generated by the renewed activation (S13) of the pressure cuffs (D1, D2) by the volume pulse detection device and displaying the volume pulse as a changed volume pulse curve; and Determining (S15) whether there is an increase in the number of peaks within the changed volume pulse curve due to the renewed control (S13) of the pressure cuffs (D1, D2).

3. Method for determining possibilities for influencing the number of peaks within a volume pulse curve of a subject (P) according to claim 2, wherein the steps of re-activating (S13) the pressure cuffs (D1, D2), detecting (S14) the changed volume pulse and determining (S15) whether due to the renewed control (S13) of the pressure cuffs (D1, D2) there is an increase in the number of peaks within the volume pulse curve, are repeated until the number of peaks within the changed volume pulse curve determined in the last step (S15) corresponds to at least two peaks, preferably three peaks or more.

4. A method for determining possible ways of influencing to increase the number of peaks within a volume pulse curve of a subject (P) according to one of claims 2 and 3, wherein the step of re-activating (S04, S13) the pressure cuffs (D1, D2) is preceded by a step (S1) of determining the time of an upper transition point of an R-wave of a cardiac cycle of the subject (P), wherein the time of the upper transition point of the R-wave is used as a temporal zero point for triggering the subsequent step (S04, S13) of re-activating the pressure cuffs (D1, D2) in order to set the re-activation (S04, S13) of the pressure cuffs (D1, D2) to a period during a diastole immediately following the R-wave.

5. A method for determining possible ways of influencing the increase in the number of peaks within a volume pulse curve of a subject (P) according to one of claims 2-4, wherein a sequence of pressure applications by the pressure cuffs (D1, D2) comprises activating at least one distal pressure cuff (D2) arranged on an extremity of the subject (P) with subsequent activation of at least one proximal pressure cuff (D1) arranged on the same extremity of the subject (P) or activating at least one proximal pressure cuff (D1) arranged on an extremity of the subject (P) with subsequent activation of at least one distal pressure cuff (D2) arranged on the same extremity of the subject (P), and / or a change in the time interval (ts) between the pressure applications by the pressure cuffs (D1,D2) comprises a temporal overlap of a control of at least one distal pressure cuff (D2) arranged on an extremity of the subject (P) and a control of at least one proximal pressure cuff (D1) arranged on the same extremity of the subject (P), preferably wherein the change in the temporal, Distance (ts) between the pressurizations by the pressure cuffs (D1, D2) comprises a temporal overlap of the pressure holding times (t?, t4) of at least two pressure cuffs (D1, D2).

6. A method for determining possible ways of increasing the number of peaks within a volume pulse curve of a subject (P) according to any one of the preceding claims, wherein a peak represents an abrupt increase in the pressure of the volume pulse curve or an abrupt decrease in the pressure of the volume pulse curve, and / or both the initial volume pulse curve of the subject (P) and the changed volume pulse curve of the subject (P) are based on volume flows detected by the volume pulse detection device in the same microcirculation area of ​​the subject (P).

7. A method for determining influencing possibilities for increasing the number of peaks within a volume pulse curve of a subject (P) according to any one of the preceding claims, wherein the method further comprises a step (S16) of determining an enlargement of vascular endothelial cells of the subject (P) due to the increase in the number of peaks.

8. A method for determining a pressure cuff control plan for a subject (P), wherein the method for determining influencing options for increasing the number of peaks within a volume pulse curve of a subject (P) according to one of claims 2-6 is used to determine (S15) whether there is an increase in the number of peaks within a volume pulse curve in the detected changed volume pulse curve profile of the subject (P), and wherein, if the renewed control (S13) of the pressure cuffs (D1, D2) leads to an increase in the peak frequency, the change in the control parameters responsible for this is used as the basis for the pressure cuff control plan of the subject (P).

9. A method for determining a pressure cuff control plan for a subject (P) according to claim 8, wherein a schedule for pressure cuff activation is determined as a function of an upper transition point of an R-wave of a cardiac cycle of the subject (P), and wherein the time of the upper transition point of the R-wave is used as the temporal zero point for the subsequent step of reactivating (S06) the pressure cuffs (D1, D2) in order to set the reactivation (S06) of the pressure cuffs (D1, D2) to a period during a diastole immediately following the R-wave, and / or wherein a pressure to be applied by the pressure cuffs (D1, D2) to the extremity of the subject (P) lies in a range from 80 mmHg to 180 mmHg, preferably with an accuracy of ± 15 mmHG.

10. A method for determining a pressure cuff control plan for a subject (P) according to one of claims 8 or 9, wherein, in addition to controlling the pressure cuffs (D1, D2) due to the change in the control parameters leading to an increase in the peak frequency, controlling a further pressure cuff (D3) is used as a basis for determining the pressure cuff control plan of the subject (P), wherein the pressure cuff (D1) and / or the at least one further pressure cuff (D2) is arranged on an extremity of the subject, and wherein the further pressure cuff (D3) is arranged on the extremity of the subject (P) at a location that is more distal than the previously used pressure cuffs (D1, D2), wherein preferably only the further pressure cuff (D3) is controlled exclusively during a period in which the control of the previously used pressure cuffs (D1, D2) is paused,wherein furthermore preferably the further pressure cuff (D3) is controlled exclusively during the period in which the control of the previously used pressure cuffs (D1, D2) is paused, with a low pressure below 80 mmHg, preferably 60 mmHg, over a fixed period of time (te), which lasts over several cardiac cycles.

11. Device for controlling pressure cuffs (D1, D2, D3) provided on a subject (P), with several independently controllable pressure cuffs (D1, D2, D3); a cardiac cycle detection device for determining the temporal position of a cardiac cycle, in particular an electrocardiogram (ECG) device, further in particular a 3-channel ECG recording device; a volume pulse detection device for detecting volume pulses in the microcirculation of the subject (P) and displaying the volume pulse as a volume pulse curve, preferably in the form of an optical plethysmography sensor; and a control unit for controlling the pressure cuffs (D1, D2, D3), wherein the control unit is designed to control the pressure cuffs (D1, D2, D3) during a diastole of the determined cardiac cycle according to a pressure cuff control plan defined using the method according to one of claims 8 to 10.

12. Use of a device according to claim 11 for carrying out a pressure cuff control plan determined by the method according to any one of claims 8 to 10.

13. The method according to any one of claims 1 to 10, wherein the method is a computer-implemented method.

14. A data processing device comprising means for carrying out the method according to claim 13.

15. A computer program product or computer-readable medium comprising instructions which, when executed by a computer, cause the computer to carry out the method of claim 13.

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