Methods and systems for treating, reducing or preventing post-ischemic reperfusion injury

Abstract

Devices, methods, and systems for providing interaction components for deoxygenated blood for the treatment or prevention of reperfusion injury, including the function of increasing the likelihood that the deoxygenated blood has an ionized calcium concentration of less than 0.5 mmol / L. System components may include one or more injection pumps in operative communication with various functions via a controller / processor, including: a cannula, a pump in communication with the cannula; a heat exchanger; means for generating / generating a fluid flow; one or more infusion ports; a mixing port; a device hub; a catheter interface; the present invention relates to a sensor that may be selectively connected to an object that optionally has one or more monitoring and / or other leads / devices attached thereto. The leads / devices may include sensors and / or other devices that may be attached / connected to the subject to provide health indicators, such as temperature sensors, electrodes for monitoring electrical activity of the heart, and / or SpO2 or other sensors for monitoring blood oxygen saturation levels of the patient.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application is based upon and claims the benefit of U.S. Provisional Patent Application No. 63 / 437,304, filed on January 5, 2023, the entire contents of which are incorporated herein by reference. Technical Field

[0003] Aspects of the present disclosure relate to methods and systems for reducing reperfusion injury in post-ischemic tissue care, such as by modifying reperfusion fluid parameters. Background Art

[0004] A stroke is a serious condition in which the blood supply to part of the brain is cut off or significantly reduced, causing cell death and irreversible tissue damage. For example, a stroke can occur when a weakened blood vessel ruptures (called a hemorrhagic stroke) or when a blood vessel becomes blocked (called an ischemic stroke). Stroke is a major global health problem.

[0005] Ischemic strokes can be classified as either thrombotic or embolic. A thrombotic stroke may be caused by the formation of a thrombus (blood clot), usually around an atherosclerotic plaque. An embolic stroke may occur when an artery becomes blocked by an embolus, a mobile particle, or debris from elsewhere (such as an arterial embolism). The embolus is usually a blood clot but can also be one of several other substances, such as fat, bacteria, cancer cells, or air.

[0006] One existing method of treating ischemic stroke patients is thrombectomy, which involves mechanically removing clots too large to be broken down by thrombolytic drugs. Thrombectomy is generally more effective the sooner it is performed after a stroke. In fact, it's widely accepted in the art that the duration of cellular oxygen deprivation is crucial for a positive stroke outcome. The expression "timing is brain" is often used to describe this phenomenon.

[0007] Once the blockage in the blood vessels is cleared, blood is reintroduced to the oxygen-deprived tissues. When cells are deprived of oxygen, they typically enter a quiescent state with slow metabolism and low activity. This serves as a protective state, extending tissue life while awaiting the restoration of oxygen. Counterintuitively, uncontrolled restoration of blood flow and oxygen can cause massive cellular damage. This effect may occur because cells are returning from a quiescent state to a potentially inappropriate environment. Therefore, when blood flow is restored, ischemic damage may cease and reperfusion injury may begin. Thus, reperfusion injury can occur after ischemia.

[0008] While existing treatments, such as thrombectomy, can sometimes be very successful in eliminating the cause of a stroke, they often fail to address reperfusion injury. There remains an unmet clinical need for therapies, and systems and methods related thereto, that reduce or prevent reperfusion injury following ischemic stroke.

[0009] Although the exact clinical mechanisms of reperfusion are not fully understood, these aspects may involve calcium overload, metabolic tissue rate, and / or inflammatory responses. It is known that the carbon dioxide and oxygen concentrations of the blood may affect the damage to cells caused by the return of blood to the ischemic tissue.

[0010] Calcium reduction can be achieved by using chelating agents (such as EDTA or ethylenediaminetetraacetic acid or sodium citrate), the proportion of which can be influenced or controlled by volume and measurement. Chelation of calcium ions may reduce its bioavailability in reperfused tissues and, for example, may be used in combination with other tissue treatments to prevent edema and the "no-reflow" phenomenon.

[0011] Blood pH may influence the progression of reperfusion injury, and the addition of acids, bases, or buffer molecules may reduce reperfusion injury. Carbon dioxide gas may alter blood pH when used in the purge flow of an oxygenator.

[0012] The no-reflow phenomenon can occur when tissue swelling impedes blood flow through the capillaries in the tissue. This effect can be one of the primary causes of injury following a stroke and may prevent or inhibit the use of various therapies. In healthy subjects, pulsatile flow can be achieved through ventricular output, and flow with a pulsatile flow waveform is known to be effective in allowing flow through the capillaries. In cases of non-pulsatile flow, such as that achieved when using unmodified peristaltic and centrifugal pumps, blood flow through the capillary bed can be less efficient, and clinical problems such as "pump head" are known to occur. These problems can be more pronounced in reperfusion injury, where, for example, edema may inhibit capillary flow.

[0013] The metabolic rate of tissues depends on their temperature, and it is well known that cooling of reperfused tissues can reduce the damage expected under normothermic conditions. The timeliness of this cooling is often crucial, and temperature values ​​may decrease as reperfusion injury progresses.

[0014] Osmolarity is the number of moles of solute per liter of solvent. In membrane science, osmosis is the equilibrium between regions of low and high osmotic pressure, as found across cell membranes. Therefore, altering the osmolarity of the reperfusion fluid may control the diffusion of these solutes across cell membranes and potentially have neuroprotective effects.

[0015] It has previously been found that the use of neuroprotective infusions and drugs with specific cellular effects to treat reperfusion injury has no benefit in “real-world” applications. For example, this finding may be due in part to the overwhelming injurious effects of arterial blood on reperfused tissue, and the ability to reduce the injurious effects of arterial blood during reperfusion may enable pharmacological interventions that were previously impossible or difficult to implement.

[0016] Immune engagement during reperfusion may result in the triggering of inflammatory pathways when the circulating immune system detects cellular contents. The ability to reduce the damage caused by this inflammatory immune response could be achieved through pharmacological means or by eliminating circulating immune cells through specialized filters.

[0017] Many existing perfusion systems have system flow rates ranging from 4000 ml / min to >7000 ml / min, making them unsuitable for single-organ reperfusion due to the mismatch between the size and surface area of ​​the interface and the internal volume of the device and the blood flow required for a single organ. Excessive gas exchange surface area for a given blood flow may result in the introduction of additional oxygenated species, leading to free radical damage in the reperfused tissue.

[0018] Typically, single-organ preservation circuits are created to preserve organs ex vivo for transplantation; for example, these circuits may lack the safety features required for in vivo use because there is no concern about damage to other organs. In situations where fluids are to be returned to the vascular circulation, the ability to prevent, detect, or eliminate microbubbles and thrombi in the fluid may be crucial.

[0019] Relying on the introduction of an insulated catheter or sensor catheter to reintroduce the cooling fluid is known in the art; however, such designs are limited by: (1) the necessity of size compatibility with existing catheters on the market (e.g., balloon catheters); or (2) if the catheter is delivered after removal of the in-line catheter, there is a risk that normothermic arterial blood, rich in calcium, could reach the tissue prior to interventional reperfusion and potentially cause damage. The ability to interface with a standard Luer port on existing catheters is advantageous because it prevents both of these issues.

[0020] The mechanisms that lead to reperfusion injury are complex and are known to follow a temporal sequence, with injurious substances causing damage at different times depending on their rate of injury. For example, calcium ions diffuse across cell membranes much faster than the long-term activation of immune responses to cell damage. Therefore, controlling blood parameters to minimize reperfusion injury relies on timely control of the distribution of therapeutic blood parameters.

[0021] Reperfusion injury occurs in all tissues that are deprived of oxygen for a prolonged period. Other clinically significant examples include chronic total occlusion, myocardial infarction, and limb ischemia.

[0022] Various aspects of the present disclosure provide devices, methods, and systems for addressing the above-mentioned problems and other problems of the prior art by using various interacting components to deoxygenate blood for treating or preventing reperfusion injury, including, for example, features that increase the likelihood that the deoxygenated blood will have an ionized calcium concentration below 0.5 mmol / L.

[0023] Additional advantages and novel features of these aspects will be set forth in part in the description that follows and will become apparent to those skilled in the art upon examination of the following or practice of the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In the attached figure:

[0025] Figure 1 is an example representative diagram illustrating various example components involved in one example embodiment of a blood deoxygenation system for treating or preventing reperfusion injury according to aspects of the present disclosure, including features that increase the likelihood of improving blood ionized calcium concentrations to less than 0.5 mmol / L.

[0026] Figure 2 A representative flow chart of example functions for controlling, monitoring, and / or modifying blood flow, including functions related to circulating or withdrawn venous blood, modified venous blood, and systemic blood supply, according to aspects of the present disclosure is shown.

[0027] Figure 3 A representative flow chart of example functionality for various intraoperative inputs and operational controls related to blood flow rate control according to aspects of the present disclosure is presented.

[0028] Figure 4 A representative flow chart containing example functionality for various intraoperative inputs and operational controls related to chelation rate control according to aspects of the present disclosure.

[0029] Figure 5 A representative flow chart illustrating example functionality for various intraoperative inputs and operational controls related to temperature control, in accordance with aspects of the present disclosure.

[0030] Figure 6 Representative flow charts of example functionality for various intraoperative inputs and operational controls related to gas control, according to aspects of the present disclosure, are presented.

[0031] Figure 7 A representative diagram illustrating various aspects of an example computer system capable of performing the functionality described in the example implementations according to aspects of the present disclosure is shown.

[0032] Figure 8is a representative block diagram of various example system / network components that can be used as described in example implementations according to aspects of the present disclosure.

[0033] Figure 9A and 9B Cross-sectional images are shown of various cross-sectional shapes / features of example mixing ports that may be used according to aspects of the present disclosure. DETAILED DESCRIPTION

[0034] Aspects of the present disclosure provide devices, methods, and systems for solving the above-mentioned problems and other problems of the prior art.

[0035] Figure 1-9B Various features of devices, methods, and systems for addressing such problems are presented, including features and methods for treating or preventing reperfusion injury by deoxygenating blood, whereby, among other advantages, the deoxygenated blood has an ionized calcium concentration of less than 0.5 mmol / L. This deoxygenated blood can be venous blood. It is noteworthy that the normal oxygen level in blood is approximately 100 mmHg. It is also possible to use blood products in place of or in combination with deoxygenated venous blood, provided that such blood products contain red blood cells or oxygen carrier moieties, such as synthetic or bioengineered heme molecules.

[0036] Degraded blood can be selectively administered intra-arterially or intravenously and can be administered at a determined appropriate temperature. For example, blood can be selectively administered to a subject suffering from an ischemic stroke, and the blood can be from the subject. For example, blood can be administered during reperfusion, such as after (preferably after in some cases) thrombectomy. The reperfusion event can be or include, for example, an ischemic stroke reperfusion injury, and the administration of the degraded blood can preferably occur in response to an event such as, but not limited to, a neurovascular ischemic stroke reperfusion injury.

[0037] Deoxygenated blood may optionally be administered in combination with a blood anticoagulant.

[0038] Deoxygenating the blood may optionally include administering a contrast agent, such as for radiography.

[0039] Figure 1 Various features of an example implementation of a system for addressing the above aspects and other aspects are shown. Figure 1As shown, the system 100 may include one or more of the following features: 1) one or more syringe pumps 105 in operable communication with various features of the system 100; 2) a cannula 110; 3) a pump 115 in communication with the cannula 110; 4) a heat exchanger (HEX 120); 5) an oxygenator and / or other device for generating / producing a fluid flow, such fluid including, but not limited to, one or more of oxygen, hydrogen, nitrogen, nitrous oxide, and / or carbon dioxide 130; 6) one or more infusion ports 135; 7) a mixing port 140; 8) a device connector 145; and 9) a catheter connector 150; optionally connected to 10) a patient 155, to which one or more monitoring and / or other leads / devices may be optionally connected. The leads / devices may include various sensors and / or other devices that may be attached or otherwise connected to the patient to provide health indicators, such as one or more temperature sensors, a plurality of electrodes or electrode connectors configured to be selectively mounted on electrodes to monitor the electrical activity of the heart, and / or an SpO2 or other sensor for monitoring the patient's blood oxygen saturation level.

[0040] Each of the above components / patients 105-155 can be operably connected to a controller, input / output, processor device 160 (e.g., which can include one or more processors and / or one or more networks and / or other features, as described below in conjunction with Figure 7 and Figure 8 155 and / or other inputs from each component 105-155 and selectively provide data / outputs to each component to selectively control the delivery of deoxygenated blood to the patient 155, among other functions. Alternatively or additionally, the controller 160 can be configured to access (e.g., via stored data in a local or remote data repository, such remote data being accessible via a network) information associated with one or more components 105-155 to enable interactive monitoring and control of various system functions. For example, such accessible data can include profile information for commercially available catheters, allowing the controller 160 to readily adjust flow parameters using corresponding stored profile information for catheters used in the system 100 to synchronize pulsatile flow delivery within each vessel with the patient's heartbeat. For example, in one example implementation, a user (e.g., a clinician) can select or confirm a desired delivery model / catheter information within the system, and the system 100 can then automatically or otherwise adjust, for example, pulsatile pump parameters and / or other system parameters to match the desired delivery to the detected heartbeat.

[0041] In an exemplary embodiment according to the present disclosure, venous blood (or, for example, blood or a blood substitute from a matched patient) can be introduced into the patient through, for example, an intravenous cannula (e.g., a Medtronic Bio-Medicus TM The cannula (110) is withdrawn from the venous system and passed through a pulsatile pump (e.g., Harvard Apparatus 1423 Pulsatile, manufactured by Harvard Apparatus, Inc., Holliston, MA) (115) to a heat exchanger (e.g., Terumo Cardiovascular, Inc., Ann Arbor, MI). Cardioplegic fluid heat exchanger (120). The flow rate and blood temperature can be used to control the temperature within the heat exchanger (120). Sensors can read the blood temperature and flow rate to inform the controller (160) to adjust the mixing of the purge gas through the oxygenator or other fluid generation / flow delivery device (130). The flow rate on the outlet side of the fluid generation / flow delivery device (130) can be measured and sent to the controller (160) to adjust the rate of addition of the chelating agent through the infusion port (135) by adjusting the syringe pump (105). The blood can be passed through the mixing port (140) (e.g., see Figure 9A and Figure 9B , including cross-sectional images of various cross-sectional shapes / features of example mixing ports that can be used according to aspects of the present disclosure) to ensure uniform distribution of the chelating agent in the reperfusion fluid stream. Blood can enter the device connector (145), which can be attached to the catheter connector (150) of the guide catheter, for example. The controller (160) can adjust target parameters based on the patient's treatment needs to adjust temperature, gas, and chelation gradients, and can add additional therapies such as calcium or magnesium ions, anticoagulants, radiodetectable compounds, and / or neuroprotective drugs through the infusion port.

[0042] Figure 2-Figure 6 A representative flow chart showing various functions related to providing deoxygenated blood and / or providing other input / output / control related thereto, according to aspects of the present disclosure, such as Figure 1 One or more functions related to an example feature.

[0043] Figure 2 A representative flow chart of example functions for controlling, monitoring, and / or modifying blood flow, including functions related to circulating or withdrawn venous blood, modified venous blood, and systemic blood supply, according to aspects of the present disclosure is shown.

[0044] Figure 3A representative flow chart of example functionality for various intraoperative inputs and operational controls related to blood flow rate control according to aspects of the present disclosure is presented.

[0045] Figure 4 A representative flow chart containing example functionality for various intraoperative inputs and operational controls related to chelation rate control according to aspects of the present disclosure.

[0046] Figure 5 A representative flow chart illustrating example functionality for various intraoperative inputs and operational controls related to temperature control, in accordance with aspects of the present disclosure.

[0047] Figure 6 Representative flow charts of example functionality for various intraoperative inputs and operational controls related to gas control, according to aspects of the present disclosure, are presented.

[0048] Aspects of the present disclosure may be implemented using hardware, software, or a combination thereof, and may be implemented in one or more computer systems or other processing systems. In one aspect of the present disclosure, features are directed to one or more computer systems capable of performing the functions described herein. Figure 7 Various aspects of an example of such a computer system 1900 are shown in FIG.

[0049] Computer system 1900 includes one or more processors, such as processor 1904. Processor 1904 can be coupled to a communication infrastructure 1906 (e.g., a communication bus, a crossbar, or a network). Various software aspects are described with respect to this example computer system. After reading this description, it will be apparent to those skilled in the relevant art how to implement various aspects of this description using other computer systems and / or architectures.

[0050] Computer system 1900 may include a display interface 1902 that forwards graphics, text, and other data from communication infrastructure 1906 (or from a frame buffer, not shown) for display on a display unit 1930. Computer system 1900 may include a main memory 1908, such as random access memory (RAM), and may also include a secondary memory 1910. Secondary memory 1910 may include, for example, a hard drive 1912 and / or a removable storage drive 1914, representing a floppy disk drive, a magnetic tape drive, an optical disk drive, or the like. Removable storage drive 1914 may read from and / or write to a removable storage unit 1918 in a well-known manner. Removable storage unit 1918 represents a floppy disk, a magnetic tape, an optical disk, or the like, which can be read from and written to by removable storage drive 1914. As will be appreciated, removable storage unit 1918 may include a computer-usable storage medium having computer software and / or data stored therein.

[0051] Alternative aspects may include secondary storage 1910 and may include other similar devices for allowing computer programs or other instructions to be loaded into the computer system 1900. Such devices may include, for example, a removable storage unit 1918 and an interface 1920. Such examples may include a program cartridge and cartridge interface (such as found in video game devices), a removable storage chip (such as an erasable programmable read-only memory (EPROM) or a programmable read-only memory (PROM)) and an associated socket, and other removable storage devices 1922 and interfaces 1920 that allow software and data to be transferred from the removable storage unit 1914 to the computer system 1900.

[0052] The computer system 1900 may also include a communication interface 1924. The communication interface 1924 may allow software and data to be transferred between the computer system 1900 and external devices. Examples of the communication interface 1924 may include a modem, a network interface (such as an Ethernet card), a communication port, a Personal Computer Memory Card International Association (PCMCIA) slot and card, and the like. The software and data transferred via the communication interface 1924 may be in the form of signals 1928, which may be or include electronic, electromagnetic, optical, or other signals that can be received by the communication interface 1924. These signals 1928 may be provided to the communication interface 1924 via a communication channel (e.g., a channel) 1926. The channel 1926 may carry the signals 1928 and may be implemented using a wired or cable, an optical fiber, a telephone line, a cellular link, a radio frequency (RF) link, and / or other communication channels. As used herein, the terms "computer program medium" and "computer-usable medium" generally refer to media such as a removable storage drive 1914, a hard disk installed in a hard drive 1912, and / or signals 1928. These computer program products can provide software to computer system 1900. Aspects of the present disclosure relate to such computer program products.

[0053] Computer programs (also referred to as computer control logic) can be stored in main memory 1908 and / or secondary memory 1910. Computer programs can also be received via communication interface 1924. When such computer programs are executed, they can enable computer system 1900 to perform features according to various aspects discussed herein. In particular, when the computer programs are executed, they can enable processor 1904 to perform features according to various aspects of the present disclosure. Thus, such computer programs can represent controllers of computer system 1900.

[0054] Where aspects of the present disclosure can be implemented using software, the software can be stored in a computer program product and loaded into the computer system 1900 using the removable storage drive 1914, the hard disk drive 1912, or the communication interface 1924. When executed by the processor 1904, the control logic (software) can cause the processor 1904 to perform the functions described herein. In another aspect of the present disclosure, the system can be implemented primarily in hardware using hardware components such as application specific integrated circuits (ASICs). It will be apparent to those skilled in the relevant art that a hardware state machine can be implemented to perform the functions described herein.

[0055] In another variation, aspects of the disclosure may be implemented using a combination of hardware and software.

[0056] Figure 8 is a block diagram of various example system components used in accordance with aspects of the present disclosure. Figure 8 Illustrated is a communication system 2000 useful in accordance with aspects of the present invention. Figure 4 The communication system 2000 shown in FIG. 1 includes one or more access points 2060 (also interchangeably referred to herein as one or more "users") and one or more terminals 2042. In one aspect, data used in accordance with aspects of the present disclosure is input and / or accessed by the access points 2060 via the terminals 2042, such as, for example, a personal computer (PC), a command issuing device including a graphical user interface (GUI), a minicomputer, a mainframe computer, a microcomputer, a telephone device, or a wireless device, such as a personal digital assistant (PDA), a smartphone, or other handheld wireless device, coupled to a server 2043, such as a PC, a minicomputer, a mainframe computer, a microcomputer, or other device having a processor and a data repository, and / or connected to the data repository via, for example, a network 2044 (e.g., the Internet or an intranet), and connectors 2045, 2046, 2047. The couplings 2045, 2046, 2047 may include, for example, wired, wireless, or fiber optic links. In one example, aspects of the reperfusion injury-related controller / system 2070 can be coupled to the network 2044 via coupling 2047, thereby being able to receive input data from and output data to the user server 2043 and the user 2060, thereby enabling the user to monitor and / or input information related to the operation of the controller / system. In another variation, the methods and systems according to aspects of the present disclosure can operate in a standalone environment, such as on a single terminal.

[0057] The following numbered clauses identify various aspects of this disclosure:

[0058] Article 1. A method for selectively administering treated blood or a blood substitute for treating or preventing reperfusion injury, the method comprising: selectively treating circulating or withdrawn blood or a blood substitute, wherein the selective treating comprises: modifying the circulating or withdrawn blood or a blood substitute to control the temperature of the circulating or withdrawn blood or a blood substitute; passing the modified circulating or withdrawn blood or a blood substitute through a fluid generating / flow delivery device to control dissolved gases; modifying the passing circulating or withdrawn blood or a blood substitute, wherein modifying the passing circulating or withdrawn blood or a blood substitute comprises at least one selected from the group consisting of: altering gas levels in the circulating or withdrawn blood or a blood substitute, reducing ionized calcium levels in the circulating or withdrawn blood or a blood substitute, and reducing pH levels in the circulating or withdrawn blood or a blood substitute; and monitoring the supply of circulating or withdrawn blood or a blood substitute; and delivering the modified and passing circulating or withdrawn blood or a blood substitute to a subject when the selectively treated circulating or withdrawn blood or a blood substitute contains an ionized calcium concentration of less than 0.5 mmol / L.

[0059] Clause 2. The method of claim 1, wherein the treated blood or blood substitute is venous blood.

[0060] Clause 3. The method of claim 1, wherein the treated blood or blood substitute is administered intra-arterially or intravenously.

[0061] Clause 4. The method of claim 1, wherein the treated blood or blood substitute is administered to a subject having an ischemic stroke, and wherein the modified blood or blood substitute is derived from the subject.

[0062] Clause 5. The method of claim 1, wherein modified blood or a blood substitute is administered during reperfusion.

[0063] Clause 6. The method of claim 5, wherein the modified blood or blood substitute is administered after thrombectomy.

[0064] Clause 7. The method of claim 1, wherein the modified blood or blood substitute is administered in combination with a blood anticoagulant.

[0065] Clause 8. The method of claim 1, wherein the reperfusion injury is ischemic stroke reperfusion injury.

[0066] Clause 9. The method of claim 8, wherein the ischemic stroke or reperfusion injury is neurovascular ischemic stroke reperfusion injury.

[0067] Clause 10. The method of claim 1, wherein the modified and passed circulating or withdrawn blood or blood substitute comprises a contrast agent for radiography.

[0068] Clause 11. The method of claim 1, wherein the modified and passed circulating or withdrawn blood is administered in conjunction with a contrast agent for radiography.

[0069] Article 12. A composition for treating or preventing reperfusion injury in a subject, wherein the composition comprises modified and passed circulating or withdrawn blood or a blood substitute, and at least one selected from the group consisting of a blood anticoagulant and a contrast agent for radiography.

[0070] Article 13. A system for selectively administering treated blood or a blood substitute to treat or prevent reperfusion injury, the system comprising: a catheter; a flow control device selectively operable with the catheter to induce flow of deoxygenated blood or a blood substitute through the catheter; a heat exchanger interoperable with the catheter or the flow control device for changing the temperature of the blood or the blood substitute; a fluid generation / flow delivery device for selectively administering oxygen, hydrogen, nitrous oxide, nitrogen, or carbon dioxide to the blood or the blood substitute; at least one infusion port in communication with the catheter; a mixing port in communication with the catheter; a device hub in communication with the catheter; a catheter connector in communication with the catheter; and a controller device operatively or communicatively coupled to at least one of the catheter, the flow control device, the heat exchanger, the fluid generation / flow delivery device, the at least one infusion port, the mixing port, the device hub, and the catheter for selectively treating circulating or withdrawn blood or a blood substitute The invention provides a method for selectively treating blood or a blood substitute, wherein the selectively treating blood or a blood substitute comprises: modifying the circulating or withdrawn blood or a blood substitute to control the temperature of the circulating or withdrawn blood or a blood substitute; passing the modified circulating or withdrawn blood or a blood substitute through a fluid generating / flow delivery device to control dissolved gases; modifying the circulating or withdrawn blood or a blood substitute passing therethrough, wherein modifying the circulating or withdrawn blood or a blood substitute passing therethrough comprises at least one selected from the group consisting of: changing the gas level in the circulating or withdrawn blood or a blood substitute, reducing the ionized calcium level in the circulating or withdrawn blood or a blood substitute, and reducing the pH level in the circulating or withdrawn blood or a blood substitute; and monitoring the supply of the circulating or withdrawn blood or a blood substitute; and delivering the modified and passed circulating or withdrawn blood or a blood substitute to a subject when the selectively treated circulating or withdrawn blood or a blood substitute comprises an ionized calcium concentration of less than 0.5 mmol / L.

[0071] Clause 14. The system of claim 13, wherein the catheter comprises a cannula or a pump.

[0072] Clause 15. The system of claim 13, wherein at least one of the conduit, the flow control device, the heat exchanger, the fluid generation / flow delivery device, the at least one infusion port, the mixing port, or the conduit comprises a sensor.

[0073] Although the aspects described herein are described in conjunction with the above-described exemplary aspects, various alternatives, modifications, variations, improvements, and / or substantial equivalents, whether known or currently unforeseen, will be apparent to those of ordinary skill in the art. Therefore, the above-described exemplary aspects are intended to be illustrative and not limiting. Various changes may be made without departing from the spirit and scope of the present disclosure. Therefore, this disclosure is intended to cover all known or later developed alternatives, modifications, variations, improvements, and / or substantial equivalents.

[0074] Thus, the claims are not intended to be limited to the aspects shown herein, but are to be accorded the full scope consistent with the claim language wherein, unless otherwise specified, a reference to a singular element does not mean "one and only one of" but rather "one or more." All structural and functional equivalents to the elements of the various aspects described in this disclosure that are known or later known to one of ordinary skill in the art are expressly incorporated herein by reference and are intended to be encompassed by the claims. Furthermore, nothing disclosed herein is intended to be disclosed regardless of whether or not it is expressly referenced in a claim. No claim element should be construed as a means-plus-function unless expressly referenced using the phrase "for."

[0075] Additionally, the word “example” is used herein to mean “serving as an example, instance, or illustration.” Any aspect described herein as “example” is not necessarily to be construed as preferred over other aspects. Unless expressly stated otherwise, the word “some” refers to one or more. Combinations such as “at least one of A, B, or C,” “at least one of A, B, and C,” and “A, B, C, or any combination thereof” include any combination of A, B, and / or C and may include multiples of A, multiples of B, or multiples of C. One or more members of A, B, or C may be included. Nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly cited in the claims.

[0076] The term "comprising" as used in this disclosure has an open meaning, allowing for the presence of other unspecified features. This term includes, but is not limited to, the semi-closed term "consisting essentially of" and the closed term "consisting of." Unless the context indicates otherwise, the term "comprising" can be replaced with "consisting essentially of" or "consisting of." The term "consisting primarily of" can also be used interchangeably with "consisting of."

Claims

1. A method for selectively administering treated blood or a blood substitute for treating or preventing reperfusion injury, the method comprising: Selectively processing circulating or withdrawn blood or a blood substitute, wherein the selective processing comprises: Modifications to circulating or withdrawn blood or blood substitutes to control the temperature of circulating or withdrawn blood or blood substitutes; Passing modified circulating or drawn blood or blood substitutes through a fluid generation / flow delivery device to control dissolved gases; Modifying circulating or withdrawn blood or a blood substitute, wherein modifying circulating or withdrawn blood or a blood substitute comprises at least one selected from the group consisting of: altering gas levels in the circulating or withdrawn blood or a blood substitute, reducing ionized calcium levels in the circulating or withdrawn blood or a blood substitute, and reducing pH levels in the circulating or withdrawn blood or a blood substitute; and Monitoring the supply of circulating or drawn blood or blood substitutes; and When the selectively treated circulating or drawn blood or blood substitute comprises an ionized calcium concentration of less than 0.5 mmol / L, the modified and passed circulating or drawn blood or substitute is delivered to the subject.

2. The method of claim 1, wherein the treated blood or blood substitute is venous blood.

3. The method of claim 1, wherein the treated blood or blood substitute is administered intra-arterially or intravenously.

4. The method of claim 1, wherein the treated blood or blood substitute is administered to a subject having an ischemic stroke, and wherein the modified blood or blood substitute is derived from the subject.

5. The method of claim 1, wherein the modified blood or blood substitute is administered during reperfusion.

6. The method of claim 5, wherein the modified blood or blood substitute is administered after thrombectomy.

7. The method of claim 1, wherein the modified blood or blood substitute is administered in combination with a blood anticoagulant.

8. The method of claim 1, wherein the reperfusion injury is ischemic stroke reperfusion injury.

9. The method of claim 8, wherein the ischemic stroke or reperfusion injury is neurovascular ischemic stroke reperfusion injury.

10. The method of claim 1, wherein the modified and passed circulating or withdrawn blood or blood substitute includes a contrast agent for radiography.

11. The method of claim 1, wherein the modified and passed circulating or withdrawn blood is administered in conjunction with a contrast agent for radiography.

12. A composition for treating or preventing reperfusion injury in a subject, wherein the composition comprises modified and passed circulating or withdrawn blood or a blood substitute, and at least one selected from a blood anticoagulant and a contrast agent for radiography.

13. A system for selectively administering treated blood or a blood substitute to treat or prevent reperfusion injury, the system comprising: catheter; a flow control device selectively operable with the catheter to induce flow of deoxygenated blood or a blood substitute through the catheter; Heat exchangers interoperable with catheters or flow control devices for changing the temperature of blood or blood substitutes; Fluid generation / flow delivery devices for selectively administering oxygen, hydrogen, nitrous oxide, nitrogen, or carbon dioxide to blood or blood substitutes; at least one infusion port in communication with the catheter; a mixing port in communication with the catheter; an equipment hub in communication with the conduit; a catheter connector, which is in communication with the catheter; as well as A controller device operatively or communicatively coupled to at least one of the conduit, the flow control device, the heat exchanger, the fluid generation / flow delivery device, the at least one infusion port, the mixing port, the device hub, and the conduit for selectively processing the circulating or withdrawn blood or blood substitute, wherein the selective processing of the blood or blood substitute comprises: Modifications to circulating or withdrawn blood or blood substitutes to control the temperature of circulating or withdrawn blood or blood substitutes; Passing modified circulating or drawn blood or blood substitutes through a fluid generation / flow delivery device to control dissolved gases; Modifying circulating or withdrawn blood or a blood substitute, wherein modifying the circulating or withdrawn blood or a blood substitute comprises at least one of: altering gas levels in the circulating or withdrawn blood or a blood substitute, reducing ionized calcium levels in the circulating or withdrawn blood or a blood substitute, and reducing pH levels in the circulating or withdrawn blood or a blood substitute; and Monitoring the supply of circulating or drawn blood or blood substitutes; and When the selectively treated circulating or drawn blood or blood substitute comprises an ionized calcium concentration of less than 0.5 mmol / L, the modified and passed circulating or drawn blood or substitute is delivered to the subject.

14. The system of claim 13, wherein the catheter comprises a cannula or a pump.

15. The system according to claim 13, wherein: At least one of the catheter, the flow control device, the heat exchanger, the fluid generation / flow delivery device, at least one infusion port, the mixing port, or the catheter includes a sensor.

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