Patent Publication Number: US-2023158223-A1

Title: Expandable ecmo extension cannula system

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation-in-part application of U.S. patent application Ser. No. 17/663,205, filed May 12, 2022, now U.S. Pat. No. 11,547,786, which is a continuation-in-part application of International PCT Patent Application Serial No. PCT/US2021/025461, filed Apr. 1 2021, which is a continuation-in-part application of U.S. patent application Ser. No. 16/840,284, filed Apr. 3, 2020, now U.S. Pat. No. 11,331,421, the entire contents of each of which are incorporated herein by reference. 
    
    
     FIELD OF THE INVENTION 
     This application relates generally to systems and methods for improving systemic perfusion and reducing complications during venous-arterial extracorporeal membrane oxygenation (VA-ECMO), and more specifically, for improving perfusion using an in-line connector and an extension cannula to deliver oxygenated blood directly to the thoracic aorta. 
     BACKGROUND 
     Nearly 23 million people suffer from heart failure (HF) worldwide, which affects approximately 7 million individuals in the United States with healthcare expenditures reaching nearly 40 billion dollars per year. Acute myocardial infarction (AMI) is a leading cause of HF and occurs in over 650,000 individuals per year in the United States. Despite early revascularization in AMI, for every 5% increase in infarct size, one-year mortality and HF hospitalization are increased by 20%. Paradoxically, coronary reperfusion may accelerate myocardial injury and cardiomyocyte death in AMI. Despite improvements in reperfusion time, subsequent HF remains a significant problem and new approaches are needed to reduce myocardial damage in AMI. 
     Arterial perfusion to every major organ system, including the heart, kidneys and brain, is determined by arterial pressure, blood flow, vascular tone, and intra-organ vascular resistance. When a patient experiences low arterial perfusion due to heart failure, cardiopulmonary failure, and cardiogenic or septic shock, venous-arterial extracorporeal membrane oxygenation (VA-ECMO) systems may be used to provide both circulatory and gas exchange support by augmenting the flow of oxygenated blood. See, e.g., Pavlushkov E, Berman M, Valchanov K. Cannulation techniques for extracorporeal life support. Ann Transl Med 2017;5(4):70. doi: 10.21037/atm.2016.11.47. Specifically, VA-ECMO drains blood from the venous system, oxygenates this blood outside of the patient, and then delivers oxygenated blood back to the arterial system, e.g., via the femoral artery. VA-ECMO is most commonly performed via large-bore cannulas placed in the femoral vein and femoral artery (known as peripheral VA-ECMO). VA-ECMO is an established strategy for cardiopulmonary support. Large-bore ECMO cannulae for use in adult humans generally range in diameter from 15 Fr (5.0 mm) to 25 Fr (8.3 mm) and are used to deliver life-sustaining blood flow rates of between 3 and 8 liter/min. 
     Despite increasing utilization of VA-ECMO, with nearly 5,000 extracorporeal membrane oxygenation devices in use annually in the U.S. alone, in-hospital mortality remains around 60%. One explanation for these poor outcomes is that peripherally cannulated VA-ECMO may cause kidney injury, increase the risk of stroke, and promote cerebral ischemia, bleeding, and vascular injury. Further, more than one large-bore cannula may be required to achieve high flow rates needed for systemic perfusion with VA-ECMO. Cannula number and size are directly associated with increased risk of bleeding, vascular trauma, and acute limb ischemia. Finally, peripherally cannulated VA-ECMO may pressurize the entire aorta and increase pressure inside the heart, which increases ventricular wall stress and myocardial oxygen consumption, thereby expanding myocardial damage or infarct size in the setting of a heart attack and increasing fluid in the lungs thereby causing acute lung injury. Recent data also shows that VA-ECMO may cause damage to mitochondria located within the heart, which may limit myocardial recovery. To mitigate heart or lung injury, concomitant devices such as intra-aortic balloon pumps and Impella® pumps (made available by AbioMed, Danvers, Mass.) may be used concomitantly with VA-ECMO and require additional vascular puncture. All of these complications are associated with increased mortality, long-term morbidity, length of stay in the hospital, and healthcare costs. New approaches to limit complications associated with VA-ECMO are required. 
     Studies indicate that VA-ECMO support may decrease kidney function and even cause acute kidney injury due to increased arterial pressure and loss of pulsatile flow to the kidney resulting from the high rates of blood flow localized to the outlet region of arterial outlet return cannulas with conventional VA-ECMO. Such injuries may in turn activate autoregulatory mechanisms of the kidneys. For example, high rates of non-pulsatile flow encountered with conventional VA-ECMO cannulas have been observed to increase vascular resistance, which in turn increases the workload of the kidneys and exacerbates oxygen consumption. Up to 70% of patients receiving VA-ECMO develop acute kidney injury, which is directly associated with mortality. Studies have further indicated that use of VA-Emay lead to a significant increase in arterial flow, as well as promote an increase in pressure within the organ itself, which in turn decreases flow in the renal vein. Thus, the net effect of VA-ECMO use, with conventional return cannulas, is an increase in pressure inside the organ, such that flow through the kidney is decreased. These physiological findings correlate with an increase in biomarkers of kidney injury, suggesting that one mechanism responsible for kidney injury may be related to pressure build-up inside the kidney and a net decrease of blood flow through the kidney. 
     Previously known efforts to reduce perfusion injury are known in the art. For example, U.S. Pat. No. 6,083,198 to Afzal describes a perfusion catheter having segmented flow regions, in which an arterial return catheter includes a series of apertures along its length to more evenly distribute blood within the aorta, including the aortic arch. One drawback of the system described in that patent, however, is that the inner catheter includes a reduced diameter than the outer catheter, thereby reducing flow rates to the distal-most portions of the catheter. 
     Recent studies also indicate that VA-ECMO use results in increased risk of stroke, e.g., acute ischemic stroke and hemorrhagic stroke. Because VA-ECMO induces retrograde blood flow in the femoral artery towards the aorta, the brain is the last major organ to receive oxygenated blood delivered via a conventional femoral artery cannula. Further, in patients exhibiting north-south syndrome, e.g., when compromised lung function results in ejection of deoxygenated blood from the left ventricle into the ascending aorta, differential hypoxia may occur as a result of VA-ECMO patients&#39; dependence on retrograde flow to deliver oxygenated blood to the upper body. To mitigate this effect, physicians currently perform additional vascular punctures in the arteries or veins to place additional large-bore cannulas that increase the risk of complications. 
     Central VA-ECMO, in which oxygenated blood is delivered directly to a central location, e.g., via a surgical cut-down to the aortic arch, has been hypothesized to provide more oxygenated blood flow to the brain and thus reduce the risk of stroke. However, such cannulation, as described for example in U.S. Pat. No. 6,210,365 to Afzal, requires invasive surgery and involves additional potential complications. Another solution theorized would be to deliver oxygenated blood directly to the venous side of the patient via an ECMO cannula; however, this would require creating additional large-bore punctures in the patient&#39;s vasculature and may be further complicated by the already existing cannula residing in the venous circulation from the original VA-ECMO configuration. Additionally, placement of rigid cannulas from the peripheral artery into a central location in the thoracic aorta may be limited by the inability to navigate large bore cannulas through the iliofemoral bifurcation, tortuous aortas, or across calcified aortas with atheromatous material lining the aorta. 
     In view of the foregoing, it would be desirable to provide systems and methods for delivering oxygenated blood via VA-ECMO from a point of entry in the femoral artery to a more central location to the patient, e.g., the thoracic aorta, to supply oxygenated blood to the brain and induce antegrade flow to lower portions of the descending aorta. Such systems and methods may thus improve blood flow to the brain, preserve brain function, reduce the risk of ischemic stroke, and reduce blood flow rates and pressures that could induce kidney injury. 
     U.S. Pat. No. 8,996,095 to Anderson describes a coronary guide extension catheter having a push member and a distal tubular member, which is configured to be positioned in a coronary artery for use during percutaneous transluminal coronary angioplasty. The guide extension catheter described in that patent is designed to stabilize the distal end of a coronary guide catheter to prevent movement away from the patient&#39;s ostium due to beating of the heart during the interventional procedure. Similarly, U.S. Pat. No. 10,485,956 to O&#39;Donovan describes a guide extension catheter having a groove in a push member and a distal shaft for guiding an interventional coronary device therethrough. Such coronary guide extension catheters are unsuitable for use as perfusion cannulas in VA-ECMO due to the small lumen diameters and resulting low blood flow rates that could be achieved. Guide extension catheters typically have a fixed diameter of between 6 Fr (2 mm) and 8 Fr (2.7 mm). These coronary guide extension catheters are not meant to redirect blood flow, but rather to facilitate delivery of coronary equipment into distal portions of the coronary vasculature. 
     U.S. Pat. No. 6,632,236 to Hogendijk describes a self-expanding catheter for use in stent delivery, in which a catheter is transluminally inserted in a collapsed delivery state, and self-expands to an expanded deployed state upon removal of a delivery sheath. That patent describes a self-expanding anchor formed of a self-expanding wire weave having an elastomeric polymeric coating, and is configured to protect against embolization during vascular interventions. The concept described in Hogendijk is not meant to redirect blood flow, but rather to filter out elements in the blood stream. Similarly, U.S. Pat. No. 6,183,443 to Kratoska describes an expandable introducer sheath for percutaneously introducing intravascular angioplasty catheters. Such self-expanding catheters have not been contemplated for use with VA-ECMO systems for perfusing oxygenated blood. 
     In view of the disadvantages of the previously known ECMO perfusion catheters, it would be desirable to provide a device for use with an ECMO system that can enhance blood flow to the thoracic aorta and aortic arch, improve cerebral oxygenation, maintain systemic arterial pulsatility, and reduce the potential for perfusion injury to the kidneys using a single port of access, thereby avoiding bleeding and vascular injury associated with contemporary VA-ECMO. 
     It further would be desirable to provide a device for use with an ECMO system that avoids the small flow lumen sizes of previously known reperfusion catheters, thereby permitting enhanced blood flow rates to the ascending aorta and aortic arch, while maintaining or reducing the diameter of the vascular opening to the femoral artery required to introduce the return cannula. 
     In contemporary practice, VA-ECMO is also used to support commonly performed life-saving procedures such as coronary angioplasty, aortic valvuloplasty, or aortic valve replacement. However, a major limitation of these approaches is the need for additional vascular access to place vascular sheaths and/or catheters for required interventional equipment in addition to the existing VA-ECMO circuit. This can be prohibitive for patients who have peripheral vascular disease, concomitant vascular injury, or vessels occupied by other life-saving equipment. Further, under emergent conditions, placing additional vascular access can be challenging and increase risk of injury. 
     U.S. Pat. Nos. 5,125,903, 5,195,980, 5,269,764, 7,938,809 describe percutaneous catheter introducers/connectors having hemostatic valves for permitting passage of elongated interventional devices into a patient&#39;s vasculature, and a side port for connection with, e.g., an outside source of perfusion, aspiration, contrast media, medicaments, etc. These systems are not designed for use with VA-ECMO. Moreover, no existing approach allows for simple and effective access to the VA-ECMO circuit for delivery of additional interventional equipment. Current Y-connectors used to provide access to an ECMO circuit suffer from numerous disadvantages including reduction in the effective lumen of the ECMO return cannula creating an undesirable pressure gradient, difficult angulations requirements that prohibit introduction of additional catheters without risk of kinking or catheter disruption. Such previously known connectors require the introducer sheath to be inserted nearly 25 to 30 cm more distal than usual due to interposition connecting tubing, thereby limiting access to the thoracic aorta, aortic root, aortic valve or coronary vasculature for therapeutic interventions. Such connectors also pose a risk of bleeding during ECMO disconnection and reconnection, with increased risk of air embolism and contamination due to disconnection from the ECMO circuit. See, e.g., Dmitriy S. Sulimov, M D et al., “Rescue Peripheral Intervention Using a Peripheral ECMO-Cannula as Vascular Access,” J Am Coll Cardiol Intv. 2020 Jan. 29. Epublished DOI:10.1016/j.jcin.2019.11.038. 
     It would therefore be desirable to provide a connector for providing simple and effective access to an ECMO circuit for delivery of interventional equipment. 
     SUMMARY OF THE INVENTION 
     In accordance with the principles of the present invention, devices and methods are provided for use with ECMO systems that overcome the disadvantages of the previously known ECMO reperfusion catheters. Specifically, devices constructed in accordance with the present invention enhance blood flow to the thoracic aorta, improve cerebral oxygenation, maintain systemic arterial pulsatility, and reduce the potential for end-organ injury. 
     In accordance with one aspect of the present invention, a kit for use with an ECMO machine is provided. The kit may include a cannula comprising a proximal region having an inlet configured to be coupled to the ECMO machine, and an outlet configured to be disposed at a location within a patient&#39;s vasculature proximal of a patient&#39;s renal vessels, and an extension cannula. The extension cannula may include a flexible conduit having a proximal end, a distal end, a length extending therebetween, and a lumen in an expanded deployed state. The flexible conduit may transition from a collapsed insertion state to the expanded deployed state when in communication with a blood flow from the ECMO machine so that the lumen forms a continuation of a blood flow path through the cannula. The extension cannula further may include an elongated shaft having a distal region coupled to the distal end of the flexible conduit. The elongated shaft may be configured to advance the flexible conduit in the collapsed insertion state to locate the distal end beyond the patient&#39;s renal vessels. The kit further may include a peel-away introducer disposed on at least a portion of the flexible conduit. The peel-away introducer may be retracted proximally relative to the flexible conduit and peeled off of the flexible conduit. Moreover, the length of the flexible conduit may be selected so that when the proximal end is located within the outlet at the location within the patient&#39;s vasculature proximal of the patient&#39;s renal vessels, the distal end extends beyond the patient&#39;s renal vessels. 
     The peel-away introducer may have a diameter that is at most equal to a diameter of the cannula. In some embodiments, the peel-away introducer may extend along an entire length of the flexible conduit. The elongated shaft may extend from the distal end of the flexible conduit proximally along a lateral side of the flexible conduit. For example, the elongated shaft may extend along the inner surface of the flexible conduit, along the outer surface of the flexible conduit, or may be embedded within the membrane of the flexible conduit. Alternatively, the elongated shaft may extend from the distal end of the flexible conduit proximally within the lumen along a longitudinal axis of the flexible conduit. For example, the elongated shaft may extend along a center portion of the lumen. The elongated shaft may be configured so that the blood flow path does not pass through the elongated shaft. Moreover, the elongated shaft may contain a hypotube which provides a lumen configured to receive a guidewire therethrough. 
     The extension cannula further may include a support coupled to a distal region of the flexible conduit. The support may extend circumferentially along the flexible conduit and may transition from a collapsed delivery state to an expanded deployed state. In addition, the extension cannula may include a plurality of connection structures extending between the distal end of the flexible conduit and the support. The plurality of connection structures may transition from a collapsed delivery state to an expanded deployed state. A distal end of the elongated shaft may include an atraumatic tip configured to be coupled to the support via the plurality of connection structures. The flexible conduit may include at least one of polyethylene, polyurethane, or nylon. Further, an outlet of the flexible conduit may include one or more pores disposed at a distal region of the flexible conduit. The proximal end of the flexible conduit may be fixedly coupled to the cannula within the outlet of the cannula. 
     The kit further may include one or more sensors disposed at a distal region of the extension cannula. The one or more sensors may be configured to measure at least one of pressure, flow, or oxygen saturation within the patient&#39;s vasculature. Accordingly, the kit further may include a console operatively coupled to the one or more sensors, the console configured to display measurements of the one or more sensors. Moreover, the elongated shaft may have a lumen sized and shaped to receive one or more electrical wires extending between the one or more sensors and the console. 
     In accordance with another aspect of the present invention, a method for improving systemic perfusion is provided. The method may include: advancing a distal end of a flexible extension cannula within a patient&#39;s vasculature via an elongated shaft coupled to the distal end of the flexible extension cannula, a proximal region of the flexible extension cannula coupled to an outlet of an ECMO return cannula in fluid communication with an ECMO machine, at least a portion of the flexible extension cannula disposed within a peel-away introducer; positioning the peel-away introducer into the patient&#39;s vasculature, such that a proximal end of the peel-away introducer remains external to the patient and the distal end of the flexible extension cannula is positioned within the patient&#39;s vasculature; retracting the peel-away introducer relative to the flexible extension cannula and peeling the peel-away introducer off of the flexible extension cannula; advancing the ECMO return cannula into the patient&#39;s vasculature such that the flexible extension cannula extends from a location proximal to the patient&#39;s renal vessels to a location beyond the patient&#39;s renal vessels; transitioning the flexible extension cannula from a collapsed insertion state to an expanded deployed state when in communication with a blood flow from the ECMO machine, the flexible extension cannula comprising a lumen in the expanded state; and delivering the blood flow through the lumen of the flexible extension cannula to the location beyond the patient&#39;s renal vessels via a plurality of pores disposed at a distal region of the flexible extension cannula to thereby improve systemic perfusion. Transitioning the flexible extension cannula from the collapsed insertion state to the expanded deployed state may include transitioning a support extending circumferentially along a distal region of the flexible extension cannula from a collapsed delivery state to an expanded deployed state, and optionally, transitioning a plurality of connection structures extending from the distal end of the flexible extension cannula to the support from a collapsed delivery state to an expanded deployed state. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.  1 A  is a side view of an exemplary extension cannula for improving reperfusion during ECMO, constructed in accordance with the principles of the present invention, with the extension conduit in a partially collapsed state. 
         FIG.  1 B  is a side view of extension cannula of  FIG.  1 A  in an expanded state. 
         FIGS.  2 A- 2 C  are schematic views illustrating use of an exemplary in-line connector with the extension cannula of  FIGS.  1 A and  1 B  in an ECMO system. 
         FIG.  2 D  is a schematic view illustrating use of the extension cannula of  FIGS.  1 A and  1 B  in an ECMO system. 
         FIG.  3    is a flow chart of exemplary steps for improving perfusion during ECMO in accordance with the principles of the present invention. 
         FIGS.  4 A and  4 B  illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of  FIGS.  1 A and  1 B . 
         FIG.  5 A  is a schematic view illustrating use of an exemplary in-line connector with an alternative exemplary extension cannula in an ECMO system, constructed in accordance with the principles of the present invention, where a proximal end of the extension cannula is coupled to a conventional ECMO cannula. 
         FIG.  5 B  is a schematic view illustrating use of the extension cannula of  FIG.  5 A  in an ECMO system without an in-line connector. 
         FIG.  5 C  is a schematic view illustrating use of an exemplary connector having a side arm with the extension cannula of  FIG.  5 A  in an ECMO system. 
         FIGS.  6 A to  6 C  are cross-sectional views of the extension cannula of  FIG.  5 B . 
         FIG.  7    is a flow chart of exemplary steps for improving perfusion during ECMO using the extension cannula of  FIGS.  5 A to  5 C  in accordance with the principles of the present invention. 
         FIGS.  8 A and  8 B  illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of  FIG.  5 B . 
         FIGS.  9 A and  9 B  illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of  FIG.  5 C . 
         FIG.  10    illustrates an alternative exemplary extension cannula in an ECMO system having one or more sensors, constructed in accordance with the principles of the present invention, where a proximal end of the extension cannula is coupled to a conventional ECMO cannula. 
         FIGS.  11 A and  11 B  are schematic views illustrating the extension cannula of  FIG.  5 B  with a peel away introducer constructed in accordance with the principles of the present invention. 
         FIG.  11 C  is a schematic view illustrating the extension cannula of  FIG.  5 C  with a peel away introducer constructed in accordance with the principles of the present invention. 
         FIG.  12    is a flow chart of exemplary steps for improving perfusion during ECMO using the extension cannula of  FIGS.  11 A to  11 C  in accordance with the principles of the present invention. 
         FIGS.  13 A to  13 D  illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of  FIG.  5 B . 
         FIGS.  14 A and  14 B  illustrate alternative extension cannulas having an external hypotube constructed in accordance with the principles of the present invention. 
         FIG.  14 C  is a cross-sectional view of the extension cannula of  FIG.  14 A . 
         FIGS.  15 A and  15 B  illustrate alternative extension cannulas having a central hypotube constructed in accordance with the principles of the present invention. 
         FIG.  15 C  is a cross-sectional view of the extension cannula of  FIG.  15 A . 
         FIG.  16 A to  16 C  illustrate various arrangements of the multiplicity of pores of the extension cannula in accordance with the principles of the present invention. 
         FIG.  17    is a graph illustrating VA-ECMO stroke risk. 
         FIG.  18    depicts north-south syndrome in a patient on ECMO. 
         FIG.  19    is a series of graphs illustrating various parameters for standard conventional ECMO cannulation compared to those achieved using alternate cannulation (delivery of blood to the thoracic aorta) in accordance with the principles of the present invention. 
         FIG.  20    is a series of graphs illustrating various parameters resulting from use of standard conventional ECMO cannulation, an Impella pump, and an exemplary system of the present invention. 
         FIG.  21    is a series of graphs representing renal arterial blood velocity obtained for standard conventional ECMO cannulation and an exemplary alternate (irrigation) cannulation system of the present invention. 
         FIG.  22    are graphs illustrating renal arterial pulsatility and renal arterial microvascular resistance for standard conventional ECMO cannulation and an exemplary alternate cannulation system of the present invention. 
         FIG.  23    is a graph showing urinary levels of kidney injury molecules associated with use of standard conventional ECMO cannulation and an exemplary alternate cannulation system of the present invention. 
         FIG.  24 A  illustrates left ventricular and right ventricular response during conventional ECMO cannulation. 
         FIG.  24 B  illustrates left ventricular and right ventricular response during ECMO using the extension cannula of the present invention. 
         FIG.  25    are graphs illustrating pressure volume area (PVA), stroke work (SW), and end-diastolic pressure (EDP) associated with use of standard conventional ECMO cannulation and an exemplary alternate cannulation system of the present invention. 
         FIG.  26 A  illustrates infarct size associated with use of standard conventional ECMO cannulation and an exemplary alternate cannulation system of the present invention. 
         FIG.  26 B  is a graph show infarct size associated with standard ischemia and reperfusion injury (IRI) and use of standard conventional ECMO cannulation and an exemplary alternate cannulation system of the present invention. 
         FIG.  27    are graphs illustrating oxygen consumption rate (OCR) associated with standard ischemia and reperfusion injury (IRI) and use of standard conventional ECMO cannulation, with and without an Impella, and an exemplary alternate cannulation system of the present invention. 
         FIG.  28    is a graph illustrating oxygen consumption rate (OCR) associated with standard ischemia and reperfusion injury (IRI) and use of standard conventional ECMO cannulation, with and without an Impella, and an exemplary alternate cannulation system of the present invention for mitochondrial complex I (CI) function. 
         FIG.  29 A  illustrates an extension cannula in an ECMO system constructed in accordance with the principles of the present invention, where a distal end of the extension cannula is disposed within the pulmonary artery and a proximal end of the extension cannula is coupled to a conventional ECMO cannula via the femoral vein. 
         FIG.  29 B  illustrates an extension cannula in an ECMO system constructed in accordance with the principles of the present invention, where a distal end of the extension cannula is disposed within the pulmonary artery and a proximal end of the extension cannula is coupled to a conventional ECMO cannula via the internal jugular vein. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Systems and methods are provided for use with ECMO systems to enhance blood flow to the thoracic aorta, ascending aorta and aortic arch, thereby facilitating normal antegrade flow to the carotid and other downstream arteries, while reducing high blood flow rates and the potential for reperfusion injury to the kidneys. The systems and methods of the present invention also may ameliorate the occurrence of north-south syndrome in patients with impaired lung function, thereby ensuring adequate flow of oxygenated blood to the patient&#39;s cerebral vasculature. 
     Referring now to  FIGS.  1 A and  1 B , an exemplary extension cannula suitable for use with a conventional VA-ECMO cannula is described. Extension cannula  10  may be constructed as described in U.S. Patent Appl. Pub. No. 2022/0280709, the entire contents of which is incorporated herein by reference. For example, extension cannula  10  may include elongated shaft  17 , e.g., a hypotube, extending between distal region  11  and proximal region  13  of extension cannula  10 . Hypotube  17  is formed of a material, e.g., stainless steel rod, having sufficient rigidity to permit extension cannula  10  to be advanced through a conventional ECMO reperfusion cannula so that distal region  11  of expandable conduit  12  may be disposed with its outlet extending beyond a patient&#39;s renal arteries, and preferably extending in a patient&#39;s ascending aorta or in the vicinity of the aortic arch. For example, hypotube  17  may have a lumen sized and shaped to receive a guidewire therethrough, such that extension cannula  10  may be advanced through the conventional ECMO reperfusion cannula to the target location over a guidewire via the lumen of hypotube  17 . Extension cannula  10  optionally may include handle  15  coupled to hypotube  17  at proximal region  13  of extension cannula  10  for maneuvering extension cannula  10 . 
     The distal end of hypotube  17  may include atraumatic tip  18 , which may be coupled to the distal region of expandable conduit  12  via connection structure  19 , e.g., one or more umbrella-like struts. Connection structure  19  may be self-expandable between a collapsed delivery state and an expanded deployed state, e.g., upon exposure from sheath  40 . As shown in  FIGS.  1 A and  1 B , connection structure  19  may have a curved shape in the expanded deployed state. Connection structure  19  may be embedded within the biocompatible material forming expanding conduit  12 . Additionally or alternatively, connection structure  19  may be coupled to the inner surface of expandable conduit  12  or to the outer surface of expandable conduit  12 , or both. Hypotube  17  does not form part of the blood flow path through the lumen of expandable conduit  12 . In one embodiment, connection structure  19  is not self-expandable, such that connection structure  19  transitions from the collapsed delivery state to the expanded deployed state when blood flows through the lumen of expandable conduit  12 , thereby causing expandable conduit  12  to fill with blood. 
     Expandable conduit  12  is made of a soft flexible material, such as polyethylene, polyurethane, or nylon, and may include pores  14  at its distal region that permit blood to perfuse through the material as the flow is directed through the lumen of expandable conduit  12 . For example, expandable conduit  12  has inlet  16  at its proximal end and an outlet, e.g., plurality of pores  14 , at its distal region, and a lumen extending therethrough for permitting blood flow. Pores  14  may be sized and shaped such that, as blood flows from the ECMO machine and through the conventional ECMO reperfusion cannula and the lumen of expandable conduit  12 , the blood flow exits expandable conduit  12  via pores  14 , while causing expandable conduit  12  to fill with blood and transition from a collapsed delivery state, as shown in  FIG.  1 A , to the expanded deployed state, as shown in  FIG.  1 B . Moreover, expandable conduit  12  has a length sufficient to extend from the outlet of the conventional ECMO reperfusion cannula to a position above the patient&#39;s renal arteries, and more preferably, into the thoracic aorta, e.g., 15-120 cm, or preferably 20-80 cm or 30-50 cm. Notably, the lightweight sock-like structure provides advantages including, for example, ease of deployment through tortuous or diseased aortas, as well as no impingement on the spinal cord as most patients are lying flat such that use of a rigid cannula may impinge on the spinal cord. 
     In addition, expandable conduit  12  may include a self-expanding support structure, e.g., anchoring stent  21 , such as a mesh, weave or braid formed of a shape-memory metal or stainless steel, at its proximal end such that anchoring stent  21  may transition from a collapsed insertion state and an expanded deployed state within the lumen of the conventional ECMO reperfusion cannula to thereby anchor expandable conduit  12  within the conventional ECMO reperfusion cannula. For example, anchoring stent  21  may be biased toward the expandable deployed state, such that anchoring stent  21  may self-expand upon exposure from sheath  40 . Anchoring stent  21  may be covered by a flexible and biocompatible covering, or alternatively, anchoring stent  21  may be uncovered. Anchoring stent  21  may be formed of a stainless steel mesh, weave or braid having a preset expanded diameter that forms a central lumen, such that expandable conduit  12  may be contracted when pulled within smaller diameter delivery sheath  40 . Alternatively, anchoring stent  21  may be a mesh, weave or braid formed of a shape-memory metal such as a nickel-titanium alloy (“Nitinol”), and having a predetermined expanded diameter that forms the internal lumen. In this way, expandable conduit  12  may be contracted to the collapsed insertion state when pulled within delivery sheath  40  as described in further detail below. 
     In the fully expanded deployed state, anchoring stent  21  assumes a diameter substantially the same as, or even larger than, the internal lumen of a conventional VA-ECMO cannula. For example, the lumen of anchoring stent  21  may be at least 15 Fr in the expanded state. Accordingly, when deployed within the lumen of the conventional ECMO cannula, anchoring stent  21  will expand to the diameter of the lumen of the conventional ECMO cannula, such that anchoring stent  21  will apply a radially outward force against the inner surface of the conventional ECMO cannula to thereby anchor anchoring stent  21  within the lumen of the conventional ECMO cannula. When inserted through a conventional ECMO cannula and anchored to the conventional ECMO cannula via anchoring stent  21 , expandable conduit  12  permits enhanced blood flow to the ascending aorta and aortic arch, while maintaining the diameter of the vascular opening in the femoral artery required to introduce the conventional VA-ECMO return cannula. In some embodiments, the biocompatible polymer coating may include additional pores proximal to pores  14  that permit blood to perfuse laterally through the material, thereby reducing jetting from pores  14 . Like self-expanding conduit  12 , expandable conduit  12  may include one or more radiopaque markers disposed along the distal end of expandable conduit  12  adjacent pores  14  to permit its location to be determined fluoroscopically. 
     In some embodiments, inlet  16  at the proximal end of expandable conduit  12  may have a feature for facilitating recapture of expandable conduit  12  within the delivery sheath. For example, expandable conduit  12  may have a plurality of angled legs that couple anchoring stent  21  of expandable conduit  12  to shaft  17  to facilitate resheathing of expandable conduit  12  for removal. Preferably, the angled legs are flexible and of uniform length, so that when the distal end of sheath  40  is advanced over the angled legs, the legs flex inward to cause anchoring stent  21  to collapse inward toward its collapsed delivery state. Alternatively, when expandable conduit  12  does not have a feature for facilitating recapture of expandable conduit  12 , expandable conduit  12  may be removed along with the conventional ECMO cannula by turning off the ECMO machine to stop blood flow into expandable conduit  12 , thereby causing expandable conduit  12  to return to a semi-collapsed state. Accordingly, expandable conduit  12  and the conventional ECMO cannula may be removed together from the patient&#39;s vasculature. 
     In some embodiments, sheath  40  may have a rapid exchange configuration, with sheath  40  having a length suitable for covering the entire length of expandable conduit  12  but is joined to a support shaft and a handle coupled to the end of the support shaft. In this manner, sheath  40  may be back-loaded over the proximal end of shaft  17  of extension cannula  10  and manipulated using the support shaft via the handle, without interfering with the ability to manipulate the proximal end of shaft  17 . 
     Referring now to  FIGS.  2 A to  2 C , operation of the embodiment of the extension cannula of  FIGS.  1 A and  1 B  is schematically depicted in conjunction with an optional in-line connector  20 , as described in U.S. Pat. No. 11,331,421, the entire contents of which are incorporated by reference. For example, in-line connector  20  has first branch inlet  22  configured to be coupled to an outlet of a conventional ECMO machine for receiving oxygenated blood from an ECMO circuit, second branch inlet  26  having a hemostatic valve welded therein, and outlet  24  configured to be coupled to a conventional ECMO cannula. First branch inlet  22  and second branch inlet  26  each are in fluid communication with outlet  24 , and each may include an optional hemostatic valve  25 . The fluid pathway extending between first branch inlet  22  and outlet  24  thus permits oxygenated blood received from an ECMO circuit to flow to through the conventional ECMO cannula and self-expanding conduit  12 . Moreover, the fluid pathway extending between second branch inlet  26  and outlet  24  is sized and shaped to permit delivery therethrough of self-expanding conduit  12  in a collapsed insertion state, e.g., when disposed within delivery sheath  40 . 
     Conventional ECMO cannula  50  may be coupled to outlet  24  of in-line connector  20  and inserted into a patient&#39;s arterial vasculature, e.g., via a cut down to the femoral artery, as shown in  FIG.  2 A . The outlet line from an ECMO machine may be coupled to first branch inlet  22 . As shown in  FIG.  2 B , extension cannula  10 , disposed with expandable conduit  12  in its collapsed insertion state within delivery sheath  40 , is advanced through the hemostatic valve of second branch inlet  26  of in-line connector  20 . Extension cannula  10  is positioned so that the distal end of expandable conduit  12  is disposed in the desired location, e.g., within the thoracic aorta, and the proximal end of expandable conduit  12  lies near the distal outlet of the conventional ECMO reperfusion cannula, e.g., as may be determined under fluoroscopy using, e.g., radiopaque marker bands disposed on sheath  40 . 
     The lumen of sheath  40  preferably is dimensioned to accept and retain expandable conduit  12  in its collapsed insertion state. Sheath  40  is slidably disposed over expandable conduit  12 , and accordingly anchoring stent  21  and connection structure  19 , so that sheath  40  may be retracted relative to expandable conduit  12 , thereby permitting connection structure  19  and/or anchoring stent  21  to transition from the collapsed delivery state to the expanded deployed state upon exposure from sheath  40 . 
     Referring now to  FIG.  2 C , when sheath  40  and expandable conduit  12  are positioned in the desired location as described above, sheath  40  is retracted while expandable conduit  12  is held in position by hypotube  17  and handle  15 , thereby permitting connection structure  19  and/or anchoring stent  21  to transition to their expanded, deployed states. As shown in  FIG.  2 C , in its expanded deployed state, anchoring stent  21  abuts the inner surface of conventional ECMO reperfusion cannula  50  to thereby anchor expandable conduit  12  within conventional ECMO reperfusion cannula  50 . Initially, upon retraction of sheath  40  and expansion of connection structure  19  and/or anchoring stent  21 , the portion of expandable conduit  12  between connection structure  19  and anchoring stent  21  may still be in a semi-collapsed delivery state, as shown in  FIG.  1 A . Expandable conduit  12  may fully transition to its expanded deployed state when in fluid communication with blood flow from the ECMO machine through conventional ECMO reperfusion cannula  50 , as shown in  FIG.  1 B . For example, in a fully expanded state, expandable conduit  12  may have a diameter of 10-20 mm. 
     Referring again to  FIG.  2 C , because most of the length of expandable conduit  12  extends past the distal end of conventional ECMO reperfusion cannula  50 , oxygenated blood from the ECMO machine may be delivered, e.g., via pores  14 , to regions beyond those accessible with a conventional ECMO return cannula. In one preferred embodiment of extension cannula  10 , expandable conduit  12  has a length between 15 to 120 cm or preferably, 20-80 cm or longer. In this manner, blood may be delivered in the vicinity of a patient&#39;s thoracic aorta, above the patient&#39;s renal artery ostia, to avoid high flow rates in the vicinity of the patient&#39;s renal arteries and reduce the risk of perfusion injury. In addition, if the distal end of expandable conduit  12  is disposed in the ascending aorta, as may be determined under fluoroscopy using radiopaque marker bands disposed on expandable conduit  12 , outflow from pores  14  of expandable conduit  12  can provide oxygenated blood to the cardiac arteries in the vicinity of the aortic root and also provide antegrade flow to the carotid arteries and downstream arteries. Accordingly, ECMO reperfusion cannula  50  may be shortened compared with conventional ECMO cannulas, e.g., 5-15 cm, or preferably 8-10 cm. 
     As described above, when the patient is to be removed from ECMO, sheath  40  may be re-inserted over shaft  17  and advanced to collapse and retrieve expandable conduit  12 . In this case, sheath  40  will first engage the plurality of angled legs that couple anchoring stent  21  of expandable conduit  12  to shaft  17 , such that advancement of sheath  40  while retaining shaft  17  stationary will cause anchoring stent  21 , and accordingly expandable conduit  12 , to collapse inward and return to its reduced diameter, collapsed insertion state within sheath  40 . As sheath  40  is further advanced distally over expandable conduit  12 , sheath  40  will engage with and cause connection structure  19  to collapse inward and return to its collapsed insertion state, such that expandable conduit  12  is disposed within sheath  40 . Extension cannula  10  and sheath  40  may then be removed through the hemostatic valve within second branch inlet  26 . 
       FIG.  2 D  illustrates extension cannula  10  coupled to conventional ECMO reperfusion cannula  50  without in-line connector  20 . As described above, in-line connector  20  is optional. Accordingly, the proximal end of conventional ECMO reperfusion cannula  50  may be coupled directly to the ECMO circuit. 
     Referring now to  FIG.  3   , a flow chart of exemplary steps for improving perfusion during ECMO in accordance with the principles of the present invention is provided. Some of the steps of method  30  may be further elaborated by referring to  FIGS.  4 A and  4 B . Initially, the distal region of extension cannula  10  may be delivered to the target location within the thoracic aorta in a collapsed insertion state within sheath  40 . For example, conventional ECMO cannula  50  may be inserted through the patient&#39;s femoral artery FA. Preferably, conventional ECMO cannula  50  is not yet coupled to ECMO machine  51  at this stage. Next, guidewire  41  may be inserted through ECMO cannula  50  until the distal end of guidewire  41  is advanced to the desired location within the patient&#39;s vasculature, e.g., within the thoracic aorta TA such as within the ascending aorta or in the vicinity of the aortic arch. At step  31 , the distal end of sheath  40 , having expandable conduit  12  disposed therein in a collapsed insertion state, is advanced through ECMO cannula  50 , e.g., over guidewire  41 , via the lumen of hypotube  17 . The distal end of sheath  40  may then be advanced until it is positioned at the desired central location within the patient&#39;s vasculature at step  32 . Guidewire  41  may then be removed through the proximal end of hypotube  17 . 
     At step  33 , sheath  40  is retracted relative to expandable conduit  12  slidably disposed within the lumen of sheath  40 , while expandable conduit  12  remains stationary, causing connection structure  19 , and accordingly at least a portion of expandable conduit  12 , to transition from the collapsed insertion state to an expanded deployed state upon exposure from sheath  40 , as shown in  FIG.  4 A .  FIG.  4 A  illustrates expandable conduit  12  in a semi-expanded state within the patient&#39;s vasculature. Sheath  40  is further retracted relative to expandable conduit  12 , causing anchoring stent  21  to transition from the collapsed insertion state to an expanded deployed state upon exposure from sheath  40  within ECMO cannula  50 , thereby anchoring expandable conduit  12  to ECMO cannula  50 . The proximal end of ECMO cannula  50  may then be coupled to ECMO machine  51 , e.g., via tubing. 
       FIG.  4 B  illustrates expandable conduit  12  fully expanded within the patient&#39;s vasculature, e.g., when expandable conduit  12  is fully exposed from sheath  40  and blood flows from ECMO machine  51  through ECMO cannula  50  and into the lumen of expandable conduit  12 . As described above, when expandable conduit  12  is fully deployed within the patient&#39;s vasculature, at step  34 , oxygenated blood may be perfused from ECMO cannula  50  to the central location within the patient&#39;s vasculature, e.g., within the ascending aorta or in the vicinity of the aortic arch, via pores  14  at the distal region of expandable conduit  12 . When the ECMO therapy is complete, at step  35 , expandable conduit  12  may be returned to the collapsed insertion state within the lumen of sheath  40  as described above, and at step  36 , sheath  40  and expandable conduit  12  disposed therein may be removed from the patient. 
     Referring now to  FIG.  5 A , another alternative exemplary extension cannula is provided. Extension cannula  10 ′ may be constructed similar to the extension cannula  10 , except that the proximal end of expandable conduit  12 ′ may be fixed to conventional ECMO reperfusion cannula  50 ′ prior to insertion of extension cannula  10 ′ into the patient. For example, as shown in  FIG.  5 A , the proximal end of expandable conduit  12 ′ may be coupled to the inner surface of conventional ECMO reperfusion cannula  50 ′ via coupling mechanism  23 , e.g., an adhesive. Accordingly, extension cannula  10 ′, conventional ECMO reperfusion cannula  50 ′, and in-line connector  20 , are advanced together into the patient, e.g., by guiding tip  18 ′ of extension cannula  10 ′ via hypotube  17 ′, to position pores  14 ′ of expandable conduit  12 ′ in the vicinity of the aortic root, as described in further detail below. 
       FIG.  5 B  illustrates extension cannula  10 ′ coupled to conventional ECMO reperfusion cannula  50 ′ without in-line connector  20 . As described above, in-line connector  20  is optional. Accordingly, the proximal end of conventional ECMO reperfusion cannula  50 ′ may be coupled directly to the ECMO circuit. As shown in  FIGS.  6 A to  6 C , hypotube  17 ′ may be positioned on a single side within the lumens of expandable conduit  12 ′ and ECMO cannula  50 ′. Specifically,  FIG.  6 A  illustrates a cross-sectional view of extension cannula  10 ′ along line A-A of  FIG.  5 B ,  FIG.  6 B  illustrates a cross-sectional view of extension cannula  10 ′ along line B-B of  FIG.  5 B , and  FIG.  6 C  illustrates a cross-sectional view of extension cannula  10 ′ along line C-C of  FIG.  5 B . As shown in  FIG.  6 A , hypotube  17 ′ may be positioned against an inner wall of ECMO cannula  50 ′ within the proximal region of ECMO cannula  50 ′. As shown in  FIG.  6 B , hypotube  17 ′ may be positioned against an inner wall of expandable conduit  12 ′ within the distal region of ECMO cannula  50 ′, e.g., adjacent to where expandable conduit  12 ′ is coupled to ECMO cannula  50 ′ via coupling mechanism  81 . As shown in  FIG.  6 C , hypotube  17 ′ may be positioned against an inner wall of expandable conduit  12 ′ throughout the length of expandable conduit  12 ′. Accordingly, hypotube  17 ′ may extend from tip  18 ′, and along an inner surface of hypotube  17 ′ toward ECMO cannula  50 ′. 
     Referring now to  FIG.  5 C , another exemplary connector for use with the extension cannulas described herein is provided. Connector  70  may have inlet  72  configured to be coupled to an outlet of a conventional ECMO machine for receiving oxygenated blood from an ECMO circuit, sidearm  73  extending at an angle from a side of connector  70 , and outlet  71  configured to be coupled to a conventional ECMO cannula. Inlet  72  is in fluid communication with outlet  71 , and may include an optional hemostatic valve. The fluid pathway extending between inlet  72  and outlet  71  thus permits oxygenated blood received from an ECMO circuit to flow to through the conventional ECMO cannula and expandable conduit  12 ″. As shown in  FIG.  5 C , inlet  72  may be co-linear with outlet  71 . Moreover, sidearm  73  is in fluid communication with the lumen of hypotube  17 ″, and also may have an optional hemostatic valve welded therein. Accordingly, sidearm  73  may have a lumen sized and shaped to receive a guidewire therethrough. In addition, sidearm  73  and hypotube  17 ″ may be sized and shaped to receive a stylet therein, the stylet configured to be inserted through sidearm  73  and hypotube  17 ″ to preserve the lumen of sidearm  73  and hypotube  17 ″ during operation and prevent clotting therein. Additionally, upon removal of the stylet, the guidewire may be reinserted through sidearm  73  and hypotube  17 ″ for removal of extension cannula  10 ″. 
     Referring now to  FIG.  7   , a flow chart of exemplary steps for improving perfusion during ECMO using any one of the extension cannulas of  FIGS.  5 A to  5 C  is provided. Some of the steps of method  70  may be further elaborated by referring to  FIGS.  8 A and  8 B , as well as  FIGS.  9 A to  9 B , as described in further detail below. As described above, expandable conduit  12 ′ is coupled to ECMO cannula  50 ′ prior to insertion of extension cannula  10 ′ and ECMO cannula  50 ′ into the patient. Accordingly, referring to the extension cannula of  FIG.  5 B , hypotube  17 ′ may extend from tip  18 ′ proximally through the lumen of expandable conduit  12 ′, and the lumen of ECMO cannula  50 . Moreover, ECMO cannula  50 ′ may be directly coupled to ECMO machine  51 . Initially, guidewire  41  may be advanced through an incision in the patient&#39;s femoral artery FA until the distal end of guidewire  41  is advanced to the desired location within the patient&#39;s vasculature, e.g., within the thoracic aorta TA such as within the ascending aorta or in the vicinity of the aortic arch. 
     At step  71  the distal end of extension cannula  10 ′, e.g., tip  18 ′ of expandable conduit  12 ′, is advanced over guidewire  41  via the lumen of hypotube  17 ′, together with ECMO cannula  50 ′, as shown in  FIG.  8 A . Extension cannula  10 ′ and ECMO cannula  50  are advanced until expandable conduit  12 ′ is positioned at the desired central location within the patient&#39;s vasculature at step  72 , and ECMO cannula  50 ′ is positioned within the patient&#39;s femoral artery FA, as shown in  FIG.  8 B . Guidewire  41  may then be removed through the proximal end of ECMO cannula  50 ′, and the proximal end of ECMO cannula  50 ′ may then be coupled to ECMO machine  51 . 
     At step  73 , oxygenated blood may be perfused from ECMO machine  51  through the lumen of expandable conduit  12 ′ via ECMO cannula  50 ′, thereby causing expandable conduit  12 ′ to fully expanded within the patient&#39;s vasculature as shown in  FIG.  8 B , to the central location within the patient&#39;s vasculature, e.g., within the ascending aorta or in the vicinity of the aortic arch, via pores  14 ′ at the distal region of expandable conduit  12 ′. As will be understood by a person of ordinary skill in the art, pores  14 ′ of expandable conduit  12 ′ may be positioned within the descending aorta, e.g., the portion of the descending aorta approaching the level of the diaphragm from beneath the thoracic cavity or the portion of the descending aorta above the diaphragm. When the ECMO therapy is complete, at step  74 , the ECMO machine may be turned off, such that blood no longer flows through expandable conduit  12 ′, thereby causing expandable conduit  12 ′ to return to a semi-collapsed state, and at step  75 , extension cannula  10 ′ and ECMO cannula  50 ′ may be removed from the patient. 
     Referring now to  FIGS.  9 A and  9 B , exemplary steps for improving perfusion during ECMO using the extension cannula of  FIG.  5 C  is provided. Specifically, method steps  71 - 75  of  FIG.  7    described above may be used to deliver extension cannula  10 ″ having connector  70  coupled thereto for improving perfusion during ECMO. For example, at step  71  the distal end of extension cannula  10 ″, e.g., tip  18 ″ of expandable conduit  12 ″, is advanced over guidewire  41  via the lumen of hypotube  17 ″, together with ECMO cannula  50 ″ and connector  70 , as shown in  FIG.  9 A . Extension cannula  10 ″ and ECMO cannula  50 ″ are advanced until expandable conduit  12 ″ is positioned at the desired central location within the patient&#39;s vasculature at step  72 , and ECMO cannula  50 ″ is positioned within the patient&#39;s femoral artery FA, such that guidewire  41  extends out of sidearm  73 . Guidewire  41  may then be removed through sidearm  73 . A stylet may then be inserted through sidearm  73  and hypotube  17 ″, e.g., until the end of the stylet is adjacent to tip  18 ″ of extension cannula  10 ″, to thereby prevent blood from entering hypotube  17 ″ and clotting therein during operation. Alternatively, an end cap may be coupled to sidearm  73 . Inlet  72  of connector  70  may then be coupled to ECMO machine  51 , as shown in  FIG.  9 B . 
     As described above, at step  73 , oxygenated blood may be perfused from ECMO machine  51  through the lumen of expandable conduit  12 ″ via connector  70  and ECMO cannula  50 ″, thereby causing expandable conduit  12 ″ to fully expanded within the patient&#39;s vasculature as shown in  FIG.  9 B , to the central location within the patient&#39;s vasculature, e.g., within the ascending aorta or in the vicinity of the aortic arch, via pores  14 ″ at the distal region of expandable conduit  12 ″. When the ECMO therapy is complete, at step  74 , the ECMO machine may be turned off, such that blood no longer flows through expandable conduit  12 ″, thereby causing expandable conduit  12 ″ to return to a semi-collapsed state. The stylet may then be removed from sidearm  73  and hypotube  17 ″, guidewire  41  may be reinserted through sidearm  73  and hypotube  17 ″. At step  75 , extension cannula  10 ″ and ECMO cannula  50 ″ may be removed from the patient, e.g., over guidewire  41 . Existing long venous cannulas do not have a proximal side-connecting Luer lock, and thus, if such long venous cannulas were to be used in the arterial position, it would not provide antegrade perfusion of the leg. In contrast, existing arterial cannulas may include a proximal side-connecting Luer lock; however, such arterial cannulas are shorter than the existing long venous cannulas. Accordingly, the custom built extension cannulas described herein provide a proximal side connecting Luer lock on a long arterial cannula. 
     Referring now to  FIG.  10   , another alternative exemplary extension cannula is provided. Extension cannula  10 ′″ may be constructed similar to the extension cannula  10 ,  10 ′ except that extension cannula  10 ′″ may include one or more sensors  52  disposed on the distal region of expandable conduit  12 ′″ for measuring one or more physiological parameters within the patient&#39;s vasculature. For example, sensors  52  may be a pressure sensor, flow sensor, and/or an oxygen saturation sensor. Accordingly, in addition to a guidewire/stylet lumen, hypotube  17 ′″ may have another separate lumen extending therethrough, sized and shaped to receive electrical wires for coupling sensors  52  to console  53 , e.g., via sidearm  73 , for providing pressure and/or oxygen saturation readouts. 
     Referring now to  FIGS.  11 A and  11 B , a delivery system for delivering extension cannula  10 ′ is provided. As shown in  FIGS.  11 A and  11 B , at least a portion of expandable conduit  12 ′ may be disposed within peel-away introducer  80 . For example, introducer  80  may extend from tip  18 ′ of expandable conduit  12 ′ proximally toward the proximal region of expandable conduit  12 ′. Preferably, introducer  80  extends along only a portion of expandable conduit  12 ′. Alternatively, introducer  80  may extend along the entire length of expandable conduit  12 ′. Introducer  80  preferably has a diameter that is equal to or slightly less than the diameter of ECMO cannula  50 ′, such that when introducer  80  is inserted through the patient&#39;s skin and into the artery, the arterial puncture is not larger than EMCO cannula  50 ′ and insertion of ECMO cannula  50 ′ into the arteriotomy after the peel-away introducer has been removed will be hemostatic without bleeding. Introducer  80  may be retracted proximally relative to expandable conduit  12 ′ and peeled away from its proximal end as shown in  FIG.  11 B , external to the patient. 
     As shown in  FIG.  11 C , peel-away introducer  80  also may be used to facilitate delivery of extension cannula  10 ″ through the patient&#39;s skin and into the artery. For example, as shown in  FIG.  11 C , introducer  80  may extend from tip  18 ″ of expandable conduit  12 ″ proximally toward the proximal region of expandable conduit  12 ″. Preferably, introducer  80  extends along only a portion of expandable conduit  12 ″. Alternatively, introducer  80  may extend along the entire length of expandable conduit  12 ″. As will be understood by a person having ordinary skill in the art, peel-away introducer may be used to facilitate delivery of the other extension cannulas described herein where the expandable conduit is prefixed to the ECMO cannula. For example, introducer  80  may be used to deliver the extension cannulas described herein that are coupled to in-line connector  20 . 
     Referring now to  FIG.  12   , a flow chart of exemplary steps for improving perfusion during ECMO using the delivery system of any one of  FIGS.  11 A to  11 C  is provided. Some of the steps of method  120  may be further elaborated by referring to  FIGS.  13 A to  13 D , as described in further detail below. As described above, at least a portion of expandable conduit  12 ′ is disposed within peel-away introducer  80 , such that introducer  80  extends from tip  18 ′ proximally towards the proximal region of expandable conduit  12 ′. Initially, guidewire  41  may be advanced through an incision in the patient&#39;s femoral artery FA until the distal end of guidewire  41  is advanced to the desired location within the patient&#39;s vasculature, e.g., within the thoracic aorta TA such as within the ascending aorta or in the vicinity of the aortic arch. 
     At step  121  the distal end of extension cannula  10 ′, e.g., tip  18 ′ of expandable conduit  12 ′, disposed within introducer  80 , is advanced over guidewire  41  via the lumen of hypotube  17 ′, together with ECMO cannula  50 ′, as shown in  FIG.  13 A . At step  122 , extension cannula  10 ′, introducer  80 , and ECMO cannula  50 ′ are advanced until introducer  80  is positioned through the patient&#39;s skin S and through femoral artery FA, such that the distal end of expandable conduit  12 ′ is disposed within the artery. The proximal end of introducer  80  will remain external to the patient. As described above, introducer  80  may be disposed over only a portion of expandable conduit  12 ′, and thus, when introducer  80  is inserted through the patient&#39;s vasculature as far as it can be while its proximal end remains external to the patient, the distal end of expandable conduit  12 ′ may not yet be disposed within the desired location within the patient&#39;s vasculature, e.g., within the vicinity of the aortic arch. 
     At step  123 , introducer  80  may be retracted proximally relative to expandable conduit  12 ′, while expandable conduit  12 ′ remains stationary within the patient&#39;s vasculature. As introducer  80  is retracted, it may simultaneously be peeled away from expandable conduit  12 ′ along its proximal end, as shown in  FIG.  13 B , until introducer  80  is completely removed from expandable conduit  12 ′, as shown in  FIG.  13 C . Once introducer  80  is completely removed from expandable conduit  12 ′, at step  124 , the extension cannula may be further inserted into the patient until the distal end of expandable conduit  12 ′ is positioned at the desired central location within the patient&#39;s vasculature, and ECMO cannula  50 ′ is positioned within the patient&#39;s femoral artery FA, as shown in  FIG.  13 D . Guidewire  41  may then be removed through the proximal end of ECMO cannula  50 ′, and the proximal end of ECMO cannula  50 ′ may then be coupled to ECMO machine  51 . 
     At step  125 , oxygenated blood may be perfused from ECMO machine  51  through the lumen of expandable conduit  12 ′ via ECMO cannula  50 ′, thereby causing expandable conduit  12 ′ to fully expanded within the patient&#39;s vasculature as shown in  FIG.  13 D , to the central location within the patient&#39;s vasculature, e.g., within the ascending aorta or in the vicinity of the aortic arch, via pores  14 ′ at the distal region of expandable conduit  12 ′. As will be understood by a person of ordinary skill in the art, pores  14 ′ of expandable conduit  12 ′ may be positioned within the descending aorta, e.g., the portion of the descending aorta approaching the level of the diaphragm from beneath the thoracic cavity or the portion of the descending aorta above the diaphragm. When the ECMO therapy is complete, at step  126 , the ECMO machine may be turned off, such that blood no longer flows through expandable conduit  12 ′, thereby causing expandable conduit  12 ′ to return to a semi-collapsed state, and at step  127 , extension cannula  10 ′ and ECMO cannula  50 ′ may be removed from the patient. 
     As described above, in some embodiments, introducer  80  may extend along the entire length of expandable conduit  12 ′. Accordingly, when introducer  80  is inserted through the patient&#39;s vasculature as far as it can be while its proximal end remains external to the patient, the distal end of expandable conduit  12 ′ may be disposed within the desired location within the patient&#39;s vasculature, e.g., within the vicinity of the aortic arch, such that upon removal of introducer  80  from expandable conduit  12 ′, the extension cannula only needs to be further inserted into the patient until ECMO cannula  50 ′ is positioned within the patient&#39;s femoral artery FA. 
     Referring now to  FIG.  14 A , an additional alternative extension cannula is provided. As shown in  FIG.  14 A , extension cannula  90  may include expandable conduit  92  and elongated shaft  93 , e.g., a hypotube, extending from tip  91  at the distal end of extension cannula  90  towards the proximal end of extension cannula  90 . Hypotube  93  is formed of a material, e.g., stainless steel rod, having sufficient rigidity to permit extension cannula  90  to be advanced through a conventional ECMO reperfusion cannula so that the distal region of expandable conduit  92  may be disposed with its outlet extending beyond a patient&#39;s renal arteries, and preferably extending in a patient&#39;s ascending aorta or in the vicinity of the aortic arch. For example, hypotube  93  may have a lumen sized and shaped to receive a guidewire therethrough, such that extension cannula  90  may be advanced through the conventional ECMO reperfusion cannula to the target location over a guidewire via the lumen of hypotube  93 . As shown in  FIG.  14 C , which is a cross-sectional view of extension cannula  90  along line C-C of  FIG.  14 A , hypotube  93  may be positioned on a single, lateral side of expandable conduit  92 . For example, as shown in  FIG.  14 C , hypotube  93  may be positioned along an inner wall of expandable conduit  92 . Accordingly, hypotube  93  may extend from tip  91 , and along an inner surface of expandable conduit  92  toward the ECMO cannula. Moreover, hypotube  93  further may extend along an inner surface of the ECMO cannula. Accordingly, hypotube  93  is not in the blood flow path through the lumen of expandable conduit  12 . In some embodiments, instead of extending from tip  91  along an inner surface of expandable conduit  12 , hypotube  93  may extend from tip  91  along an outer surface of expandable conduit  12 , and accordingly, along an outer surface of the ECMO cannula, or alternatively, hypotube  93  may be embedded within the biocompatible material forming expandable conduit  12 , e.g., the membrane of expandable conduit  12 , such that hypotube  93  extends from tip  91  and through the membrane of expandable conduit  12  towards the ECMO cannula. 
     Referring again to  FIG.  14 A , the distal end of hypotube  93  may include atraumatic tip  91 , which may be coupled to the distal region of expandable conduit  92 . In addition, as shown in  FIG.  14 A , extension cannula  90  further may include circumferential support  94  positioned at the distal region of expandable conduit  92  to facilitate expansion of expandable conduit  92  within the patient&#39;s vasculature. Support  94  may be self-expandable between a collapsed delivery state and an expanded deployed state, e.g., upon exposure from the delivery sheath. As shown in  FIG.  14 A , support  94  may have a circumferential profile in the expanded deployed state. Support  94  may be embedded within the biocompatible material forming expanding conduit  92 . Additionally or alternatively, support  94  may be coupled to the inner surface of expandable conduit  92  or to the outer surface of expandable conduit  92 , or both. Moreover, in some embodiments, support  94  may also be coupled to hypotube  93 . In one embodiment, support  94  is not self-expandable, such that support  94  transitions from the collapsed delivery state to the expanded deployed state when blood flows through the lumen of expandable conduit  94 , thereby causing expandable conduit  92  to fill with blood. In some embodiments, extension cannula  90  may not include support  94 . 
     Expandable conduit  92  is made of a soft flexible material, such as polyethylene, polyurethane, or nylon, and may include a plurality of pores  95  at its distal region that permit blood to perfuse through the material as the flow is directed through the lumen of expandable conduit  92 . Pores  95  may be sized and shaped such that, as blood flows from the ECMO machine and through the conventional ECMO reperfusion cannula and the lumen of expandable conduit  92 , the blood flow exits expandable conduit  92  via pores  95 , while causing expandable conduit  92  to fill with blood and transition from a collapsed delivery state to the expanded deployed state. In some embodiments, the biocompatible polymer coating may include additional pores proximal to pores  95  that permit blood to perfuse laterally through the material, thereby reducing jetting from pores  95 . Moreover, expandable conduit  92  has a length sufficient to extend from the outlet of the conventional ECMO reperfusion cannula to a position above the patient&#39;s renal arteries, and more preferably, into the thoracic aorta, e.g., 15-120 cm, or preferably 20-80 cm or 30-50 cm. Notably, the lightweight sock-like structure provides advantages including, for example, ease of deployment through tortuous or diseased aortas, as well as no impingement on the spinal cord as most patients are lying flat such that use of a rigid cannula may impinge on the spinal cord. 
     Referring now to  FIG.  14 B , an additional alternative extension cannula is provided. Extension cannula  90 ′ may be constructed similar to extension cannula  90 , except that extension cannula  90 ′ further may include connection structure  96 , e.g., one or more umbrella-like struts, extending between tip  91 ′ and support  94 ′ to thereby provide reinforcement support at the distal region of extension cannula  90 ′. Connection structure  96  may be self-expandable between a collapsed delivery state and an expanded deployed state, e.g., upon exposure from the delivery sheath. As shown in  FIG.  14 B , connection structure  96  may have a linear shape in the expanded deployed state. Connection structure  96  may be embedded within the biocompatible material forming expanding conduit  92 . Additionally or alternatively, connection structure  96  may be coupled to the inner surface of expandable conduit  92  or to the outer surface of expandable conduit  92 , or both. In one embodiment, connection structure  96  is not self-expandable, such that connection structure  96  transitions from the collapsed delivery state to the expanded deployed state when blood flows through the lumen of expandable conduit  92 , thereby causing expandable conduit  92  to fill with blood. 
     Referring now to  FIG.  15 A , an additional alternative extension cannula is provided. As shown in  FIG.  15 A , extension cannula  100  may include expandable conduit  102  and elongated shaft  103 , e.g., a hypotube, extending from atraumatic tip  101  at the distal end of extension cannula  100  towards the proximal end of extension cannula  100 . Hypotube  103  is formed of a material, e.g., stainless steel rod, having sufficient rigidity to permit extension cannula  100  to be advanced through a conventional ECMO reperfusion cannula so that the distal region of expandable conduit  102  may be disposed with its outlet extending beyond a patient&#39;s renal arteries, and preferably extending in a patient&#39;s ascending aorta or in the vicinity of the aortic arch. For example, hypotube  103  may have a lumen sized and shaped to receive a guidewire therethrough, such that extension cannula  100  may be advanced through the conventional ECMO reperfusion cannula to the target location over a guidewire via the lumen of hypotube  103 . As shown in  FIG.  15 C , which is a cross-sectional view of extension cannula  100  along line C-C of  FIG.  15 A , hypotube  103  may be positioned at a central position within the lumen of expandable conduit  102 . Specifically, as shown in  FIG.  15 A , hypotube  103  may extend along the longitudinal axis of extension cannula  100 , while centered within the lumen of expandable conduit  102  to provide more stability in terms of cannula movement in the aorta. Accordingly, hypotube  103  may extend from tip  101 , and through the lumen of expandable conduit  103  toward the ECMO cannula. Moreover, hypotube  103  further may extend through the lumen of the ECMO cannula. Hypotube  103  does not form part of the blood flow path through the lumen of expandable conduit  102 . 
     Expandable conduit  102  is made of a soft flexible material, such as polyethylene, polyurethane, or nylon, and may include a plurality of pores  105  at its distal region that permit blood to perfuse through the material as the flow is directed through the lumen of expandable conduit  102 . Pores  105  may be sized and shaped such that, as blood flows from the ECMO machine and through the conventional ECMO reperfusion cannula and the lumen of expandable conduit  102 , the blood flow exits expandable conduit  102  via pores  105 , while causing expandable conduit  102  to fill with blood and transition from a collapsed delivery state to the expanded deployed state. In some embodiments, the biocompatible polymer coating may include additional pores proximal to pores  105  that permit blood to perfuse laterally through the material, thereby reducing jetting from pores  105 . Moreover, expandable conduit  102  has a length sufficient to extend from the outlet of the conventional ECMO reperfusion cannula to a position above the patient&#39;s renal arteries, and more preferably, into the thoracic aorta, e.g., 15-120 cm, or preferably 20-80 cm or 30-50 cm. Notably, the lightweight sock-like structure provides advantages including, for example, ease of deployment through tortuous or diseased aortas, as well as no impingement on the spinal cord as most patients are lying flat such that use of a rigid cannula may impinge on the spinal cord. 
     Referring now to  FIG.  15 B , an additional alternative extension cannula is provided. Extension cannula  100 ′ may be constructed similar to extension cannula  100 , except that extension cannula  100 ′ further may include circumferential support  104  and connection structure  105 , e.g., one or more umbrella-like struts, extending between tip  101 ′ and support  104  to thereby provide reinforcement support at the distal region of extension cannula  100 ′. As shown in  FIG.  15 B , support  104  may be positioned at the distal region of expandable conduit  102 ′ to facilitate expansion of expandable conduit  102 ′ within the patient&#39;s vasculature. Support  104  may be self-expandable between a collapsed delivery state and an expanded deployed state, e.g., upon exposure from the delivery sheath. As shown in  FIG.  15 B , support  104  may have a circumferential profile in the expanded deployed state. Support  104  may be embedded within the biocompatible material forming expanding conduit  102 ′. Additionally or alternatively, support  104  may be coupled to the inner surface of expandable conduit  102 ′ or to the outer surface of expandable conduit  102 ′, or both. In one embodiment, support  104  is not self-expandable, such that support  104  transitions from the collapsed delivery state to the expanded deployed state when blood flows through the lumen of expandable conduit  104 , thereby causing expandable conduit  102 ′ to fill with blood. In some embodiments, extension cannula  100  of  FIG.  15 A  also may include a circumferential support. 
     Connection structure  105  may be self-expandable between a collapsed delivery state and an expanded deployed state, e.g., upon exposure from the delivery sheath. As shown in  FIG.  15 B , connection structure  105  may have a linear shape in the expanded deployed state. alternatively, connection structure  105  may have a curved shape in the expanded deployed state. Connection structure  105  may be embedded within the biocompatible material forming expanding conduit  102 ′. Additionally or alternatively, connection structure  105  may be coupled to the inner surface of expandable conduit  102 ′ or to the outer surface of expandable conduit  102 ′, or both. In one embodiment, connection structure  105  is not self-expandable, such that connection structure  105  transitions from the collapsed delivery state to the expanded deployed state when blood flows through the lumen of expandable conduit  102 ′, thereby causing expandable conduit  102 ′ to fill with blood. 
     Referring now to  FIGS.  16 A to  16 C , the extension cannulas described herein may include various arrangements and configurations of pores disposed on at least the distal region of the expandable conduit, e.g., expandable conduit  12 ,  12 ′,  12 ″,  12 ′″,  92 ,  92 ′,  102 ,  102 ′, the pores sized and shaped to permit blood flow therethrough to thereby avoid blood stasis or clotting along the length of the cannula and to more evenly distribute flow in the aorta, thereby also avoiding loading of the left ventricle. As shown in  FIG.  16 A , the plurality of pores may include first plurality of pores  14   a  and second plurality of pores  14   b , which may have a longitudinally extending shape, e.g., oval shape. Moreover, pores  14   a  and pores  14   b  may be arranged laterally along the length of at least the distal region of the expandable conduit, such that pores  14   b  are proximal to pores  14   a . In addition, pores  14   a  may be disposed spatially apart from each other along the expandable conduit by a distance that is less than the distance pores  14   b  are spatially disposed apart by along the expandable conduit. 
     As shown in  FIG.  16 B , the plurality of pores may include pores  14   c , which may have a longitudinally extending shape, e.g., oval shape, and may be equally spatially disposed from each other along the length of at least the distal region of the expandable conduit. 
     As shown in  FIG.  16 C  the plurality of pores may include first plurality of pores  14   d  and second plurality of pores  14   e . Pores  14   d  may have a circular shape, and may be disposed circumferentially about at least the distal region of the expandable conduit. As shown in  FIG.  16 C , plurality of pores  14   d  may include multiple rows of circumferentially disposed pores. Although  FIG.  16 C  illustrates four rows of circumferentially disposed pores  14   d , as will be understood by a person having ordinary skill in the art, pores  14   d  may include less or more than four rows of circumferentially disposed pores. Moreover, pores  14   e  may include multiple pores arranged laterally along the length of at least the distal region of the expandable conduit. As shown in  FIG.  16 C , pores  14   e  may be proximal to pores  14   d . As will be understood by a person having ordinary skill in the art, the plurality of pores described herein may have any combination of the arrangements and configurations described above. For example, the laterally disposed pores may have a circular shape, and the circumferentially disposed pores may have a longitudinally extending shape, or any combination thereof. 
       FIG.  17    is a graph illustrating stroke risk for patient&#39;s undergoing various therapies include VA-ECMO. As shown, a patient undergoing VA-ECMO generally has the highest risk of total stroke, e.g., acute ischemic stroke and hemorrhagic stroke. In accordance with the principles of the present invention, the systems and methods described herein are expected to provide oxygenated blood to the cerebral vasculature and provide antegrade flow from the outlet of the self-expanding conduit. This in turn is expected to reduce the risk of ischemic stroke and reduce blood flow rates and pressures that could induce kidney injury. 
     With respect to  FIG.  18   , a further expected benefit of the system and method of the present invention is described.  FIG.  18    illustrates a situation referred to as “north-south syndrome” that may arise in a patient on ECMO, particularly patients having compromised lung function. In such cases, although the heat is beating, the blood returned to circulation by the left ventricle may be poorly oxygenated. In this case, if a conventional ECMO return catheter is employed, oxygenated blood reperfused into the patient mixes with the antegrade flow of deoxygenated blood from the lungs, resulting in differential hypoxia. Because the extension cannula of the present invention is designed to deliver blood into the ascending aorta, the system and methods of the present invention are expected to significantly ameliorate the effect of compromised lung function and reduce the occurrence and severity of north-south syndrome. 
     Preclinical data from experiments utilizing an extension cannula constructed in accordance with the principles of the present invention demonstrate superior performance compared to conventional ECMO return cannulas.  FIG.  19    is a series of graphs comparing various parameters measured during standard VA-ECMO cannulation and with use of the extension cannula of the present invention (defined as “Alternate Cannulation” in  FIG.  19   ). In particular, the alternate cannulation of the present invention results in reduced pulmonary artery mean arterial pressure (MAP), reduced right arterial pressure, reduced pulmonary capillary wedge pressure, reduced renal arterial flow velocity, and reduced renal interstitial pressure (organ pressure), compared to standard VA-ECMO cannulation. These findings suggest that placement of an extension cannula may reduce cardiac, lung, and kidney injury when compared to standard VA-ECMO alone. Specifically, this data shows reduced heart pressures (right atrial pressure and pulmonary capillary wedge pressure), normal renal artery velocity, and normal renal interstitial (organ) pressures with alternate cannulation as opposed to standard cannulation (delivery of blood to the femoral artery). Further, as shown in  FIG.  20   , the alternate cannulation of the present invention provides increased pulsatile arterial flow in the renal artery and the femoral artery compared to standard VA-ECMO cannulation. Compared to sham operated animals, standard femoral cannulation ECMO reduces renal and femoral artery pulse pressure, e.g., pulsatility. Compared to standard cannulation, alternative cannulation (delivery of blood to the thoracic aorta) has increased renal and femoral artery pulse pressure, e.g., pulsatility. Improved physiologic pulsatility is further associated with less injury. 
       FIGS.  21  and  22    provide further comparisons of use of the alternate cannulation of the present invention compared to standard ECMO cannulation, demonstrating improved renal arty pulsatility and reduced microvascular resistance in the kidney. Regarding  FIG.  21   , compared to standard cannulation, alternate (irrigation) cannulation preserves pulsatility in the renal artery after three hours of pumping. Regarding  FIG.  22   , compared to standard cannulation, alternate (irrigation) cannulation preserves pulsatility (renal resistance index) and reduces renal arterial microvascular resistance in the renal artery after two and six hours of pumping. Similarly,  FIG.  23    demonstrates that the alternate cannulation of the present invention (“ALT ECMO”) results in lower levels of kidney injury molecule 1 (KIM-1) in the urine, indicating less kidney injury suffered by the patient. Compared to standard VA-ECMO, ALT ECMO is associated with lower (normal) levels of kidney injury marker in the urine. 
       FIGS.  24 A and  24 B  provide a further comparison of use of the alternate cannulation of the present invention compared to standard ECMO cannulation, demonstrating significant and unexpected reduction in both left and right ventricular workload.  FIG.  24 A  is a graph of measured Pressure versus Volume that includes traces for the left and right ventricles at 60-minutes post-infarct, immediately after commencement of arterial ECMO cannulation within the femoral artery at a standard sub-renal outlet location, and after ten minutes of standard arterial ECMO cannulation. The area within the respective Pressure versus Volume loops, referred to as “PVA”, is a measure of the work performed by the heart during the cardiac cycle. The graphs of  FIG.  24 A  show that the pressure/volume loops for the left ventricle (LV) are substantially unchanged by ECMO reperfusion. Similarly, the right ventricle (RV) also does not experience a significant reduction in workload after standard arterial ECMO cannulation. By way of possible explanation, but without intending to be limiting, it is postulated that the left and right ventricular workload is substantially unchanged because introduction of continuous high flow below the renal arteries causes the blood column in the descending aorta to stagnate, which in turn causes the LV pressures to remain high. Thus, it is believed that the heart must continue working to overcome the resistance to antegrade flow created by the ECMO-infused blood. Accordingly, during standard ECMO cannulation, femoral delivery of arterial blood pressurizes the entire aorta, thereby increasing the load against which the native heart must pump. 
     In contrast, as shown in  FIG.  24 B , when the extension cannula of the present invention is deployed to extend the ECMO outlet within the aortic arch, both the left ventricle (LV) and the right ventricle (RV) experience a significant reduction in workload after commencement of ECMO activation, and thereafter, compared to standard arterial ECMO cannulation in  FIG.  24 A . Specifically, the pressure/volume loops for the left ventricle (LV) significantly decrease, and the pressure/volume loops for the right ventricle (RV) decreases even more, thus illustrating the effectiveness of the extension cannula of the present invention in reducing cardiac workload during ECMO reperfusion. Again by way of explanation, but without intending to be limiting, it is postulated that the significant decrease in left and right ventricular workload is due to the delivery of blood into the aortic arch, which enhances antegrade blood flow to the descending aorta as well as the arteries adjoining the aortic arch. Thus, the resulting forward flow, which fully develops during the 10 minutes after commencement of ECMO reperfusion, unloads the LV, thereby causing lesser cardiac output, but at much lower pressure. Moreover, it is believed that the reduced load in the LV may assist blood transiting the lungs, further reducing RV workload. Accordingly, by delivering blood in the aortic arch, the arterial tree is not pressurized, thereby avoiding increased pressure load that the heart might otherwise have to work against, which allows for more effective venous drainage of the heart, and thus reduced RV and LV volumes, without the cost of increasing ventricular pressure. 
       FIG.  25    are graphs illustrating pressure volume area (PVA), stroke work (SW), and end-diastolic pressure (EDP) associated with use of standard conventional VA-ECMO cannulation and the alternate extension cannulation of the present invention. As shown in  FIG.  25   , despite equivalent rates of flow through the VA-ECMO circuits (bottom right), compared with standard conventional VA-ECMO, use of the alternate extension cannulation of the present invention reduces PVA, SW, and EDP, thereby evidencing that the alternate extension cannulation of the present invention reduces cardiac workflow. 
       FIG.  26 A  illustrates infarct size associated with use of standard conventional ECMO cannulation and the alternate cannulation of the present invention. As shown in  FIG.  26 B , infarct size associated with use of the alternate extension cannulation of the present invention is much lower than the infarct sizes associated with standard ischemia and reperfusion injury (IRI) and with use of standard conventional ECMO cannulation. 
       FIG.  27    are graphs illustrating oxygen consumption rate (OCR) associated with standard ischemia and reperfusion injury (IRI) and use of standard conventional ECMO cannulation, with and without an Impella device, and the alternate extension cannulation of the present invention, which is indicative of the function of the mitochondria. Mitochondria are known as the “powerhouse” of the cell, generating ATP via oxidative phosphorylation (OXPHOS) complexes, which are present in the inner membrane of mitochondria. These complexes are known as NADH: ubiquinone oxidoreductase (complex I), succinate dehydrogenase (complex II), ubiquinol—cytochrome c oxidoreductase (complex III, or cytochrome bci complex), cytochrome c oxidase (complex IV), and ATP synthase (complex V). 
     Complex I (CI) is the largest and most complicated component of the respiratory chain. Using the bovine heart as the model system, previous work has characterized all the complex I subunits and cloned the encoding genes. Mitochondrial CI accounts for 40% of proton motive force required to maintain ATP synthase in the electron transport chain (ETC). In a recent study, it was shown that reducing left heart workload with a mechanical pump can reduce myocardial damage and preserve mitochondrial CI function. See, e.g., Lija Swain, PhD, et al., Transvalvular Ventricular Unloading before Reperfusion in Acute Myocardial Infarction, Journal of the American College of Cardiology, Vol. 76, No. 6, 2020. The study further found that use of VA-ECMO during a heart attack fails to reduce left heart workload and increases myocardial damage, and significantly reduces mitochondrial CI function. This effect of VA-ECMO cannot be rescued by placing an unloading pump after VA-ECMO has been initiated. The study illustrated that using the alternate extension cannulation of the present invention with VA-ECMO reduces left heart workload, reduces myocardial damage, and improves function of mitochondrial CI. 
     For example, as shown in  FIG.  27   , compared with IRI alone, standard conventional VA-ECMO alone, and standard conventional VA-ECMO with an Impella device, use of the alternate extension cannulation of the present invention with VA-ECMO preserves function of mitochondrial CI, as measured by oxygen consumption rate (OCR), which when impaired, contributes to myocardial damage and infarct size. Moreover, as shown in  FIG.  28   , compared to the non-infarct zone, mitochondrial CI function is significantly reduced in the infarct zone after IRI alone, standard conventional VA-ECMO alone, and standard conventional VA-ECMO with an Impella device. In contrast, mitochondrial CI function is significantly higher in the infarct zone after treatment using the alternate extension cannulation of the present invention with VA-ECMO. These data identify for the first time that the point of delivery for arterial blood returning from VA-ECMO promotes a cardio-protective effect on the heart, which has implications for any patient receiving VA-ECMO and especially for patients receiving VA-ECMO who are having a heart attack or heart injury. 
     While various illustrative embodiments of the invention are described above, it will be apparent to one skilled in the art that various changes and modifications may be made therein without departing from the invention. For example, as will be understood by a person having ordinary skill in the art, the systems and methods described herein are not limited for use with a VA-ECMO system. For example, the inventive extension cannula may also be used with, e.g., a venous-venous ECMO (VV-ECMO) system. Moreover, the extension cannulas and in-line connectors described herein may be used in conjunction with a conventional ECMO drainage catheter such that the extension cannula extends from the drainage catheter at the femoral vein to within the pulmonary artery or right ventricle of the patient, thereby permitting blood to be pumped directly out of the heart, effectively functioning as a ventricular assist device. 
     As shown in  FIGS.  29 A and  29 B , any of the extension cannulas described herein, e.g., extension cannula  10 ,  10 ′,  10 ″,  10 ′″,  90 ,  90 ′,  100 ,  100 ′, may be used in conjunction with conventional ECMO drainage catheter  200  in fluid communication with ECMO drainage machine  201 , such that the pores of the expandable conduit, e.g., pores  14  of expandable conduit  12 , are disposed within the pulmonary artery PA. For example, as shown in  FIG.  29 A , the extension cannula may be inserted via a femoral vein approach and have a length such that expandable conduit  12  extends through the femoral vein, inferior vena cava IVC, right atrium RA, and right ventricle RV, and pores  14  are disposed within pulmonary artery PA. Accordingly, the extension cannula may provide right heart support by draining blood from or delivering blood to the pulmonary artery PA via pores  14  through expandable conduit  12 . In some embodiments, the extension cannula may have a length such that pores  14  are disposed within right ventricle RV, to thereby drain blood from or deliver blood to the right ventricle RV. Alternatively, the extension cannula may have a length such that the distal end of the extension cannula is disposed within pulmonary artery PA, and pores  14  are arranged at the distal region of the extension cannula such that pores  14  are disposed within both pulmonary artery PA and right ventricle RV, to thereby drain blood from or deliver blood to both pulmonary artery PA and right ventricle RV. 
     Alternatively, as shown in  FIG.  29 B , the extension cannula may be inserted via an internal jugular vein approach and have a length such that expandable conduit  12  extends through the internal jugular vein, superior vena cava SVC, right atrium RA, and right ventricle RV, and pores  14  are disposed within pulmonary artery PA. Accordingly, the extension cannula may provide right heart support by draining blood from or delivering blood to the pulmonary artery PA via pores  14  through expandable conduit  12 . In some embodiments, the extension cannula may have a length such that pores  14  are disposed within right ventricle RV, to thereby drain blood from or deliver blood to the right ventricle RV. Alternatively, the extension cannula may have a length such that the distal end of the extension cannula is disposed within pulmonary artery PA, and pores  14  are arranged at the distal region of the extension cannula such that pores  14  are disposed within both pulmonary artery PA and right ventricle RV, to thereby drain blood from or deliver blood to both pulmonary artery PA and right ventricle RV. As will be understood by a person having ordinary skill in the art, the extension cannulas described above for use with a conventional ECMO cannula for delivering oxygenated blood directly to a location above the patient&#39;s renal veins, also may have a length such that the distal end region of the extension cannula, and accordingly the pores of the expandable conduit, are disposed within the pulmonary artery and/or the right ventricle, such that oxygenated blood may be delivered directly to the pulmonary artery and/or the right ventricle, respectively. 
     The appended claims are intended to cover all such changes and modifications that fall within the true scope of the invention.