Abstract:
Devices and methods to deliver cooled fluid to an internal site in the body are disclosed. A catheter for infusing a fluid to a site internal to the body includes an elongated member having a distal end positionable to be near the internal site and a lumen extending longitudinally through the member to the distal end of the member. An element cools fluid as it flows through the lumen before the fluid exits the lumen at the distal end. A method of performing an interventional procedure includes inserting a guide catheter into an aorta and seating a distal end of the guide catheter in a coronary ostium. A lesion is treated to eliminate an impediment to blood flow through a vessel, the treatment permitting increased blood flow through the vessel. Cooled fluid is provided to the ischemic tissue region caused by the lesion.

Description:
TECHNICAL FIELD  
         [0001]    The invention relates to delivering cooled fluid to sites inside the body.  
         BACKGROUND  
         [0002]    The flow of oxygenated blood through the coronary arteries may be reduced or completely blocked by a thrombus or embolus associated with an underlying narrowing of the artery, commonly referred to as a lesion, causing acute myocardial infarction (AMI). Evidence shows that early reperfusion dramatically reduces injury to an ischemic tissue region, that is, the tissue region deprived of oxygenated blood, as the injury to the tissue continues throughout the ischemic event. Thus, early treatment of the coronary blockage using, for example, percutaneous transluminal coronary angioplasty (PTCA) or lytic therapy is desirable. Once the lesion in the coronary artery is repaired, normal blood flow may be restored to the ischemic tissue region.  
           [0003]    Reperfusion injury may occur upon the reestablishment of blood flow due to a number of factors including oxygen radical formation, microvascular plugging, inflammatory reactions, and metabolic disturbances. It is possible to reduce reperfusion injury to the ischemic tissue region by cooling the tissue before reperfusion. Mild cooling of the tissue region to a temperature of 33 degrees Celsius, which is approximately four degrees cooler than normal body temperature, provides a protective effect, likely by the reduction in the rate of chemical reactions and the reduction of tissue activity and associated metabolic demands. Although the target cooling temperature is 33 degrees, cooling the target tissue to between 28 and 36 degrees Celsius may provide benefit as well. There are also benefits to cooling the blood entering an ischemic zone, such as reducing platelet aggregation and neutrophil adhesion which decreases the likelihood of microvascular plugging.  
           [0004]    One way an ischemic tissue region in the heart may be cooled is by placing an ice pack over the patient&#39;s heart. Another method involves puncturing the pericardium and providing cooled fluid to a reservoir inserted into the pericardial space near the ischemic tissue region. In another cooling method, the target tissue is directly perfused with a cooled solution. For example, a catheter having a heat transfer element located in the catheter&#39;s distal tip may be inserted into a blood vessel to cool blood flowing into and through the heart. It is also possible to cool the ischemic tissue region by supplying cool blood to the heart through a catheter placed in the patient&#39;s coronary sinus.  
         SUMMARY  
         [0005]    The invention features devices and methods to deliver cooled fluid to an internal site in the body. A catheter for infusing a fluid to a site internal to the body is provided. The catheter includes an elongated member having a distal end positionable to be near the internal site and a lumen extending longitudinally through the member to the distal end of the member. An element cools fluid as it flows through the lumen before the fluid exits the lumen at the distal end.  
           [0006]    In embodiments, the lumen may be formed to guide a second catheter, which may be a dilation catheter or a catheter of the type used to deliver therapeutic solutions. The elongated member of the catheter may have a distal portion that includes the element and is shaped for insertion into an aorta and into the ostium of a vessel. The catheter may also include a plurality of sub-elements that cool the fluid flowing through the lumen, and flexible tubing attached to the elongated member between the sub-elements. A temperature sensor to measure the temperature of fluid flowing through the lumen that has a sensing portion located near the distal end of the elongated member may also be provided.  
           [0007]    The element may be a thermoelectric cooler having a plurality of thermoelectric semiconductors. The thermoelectric semiconductors may be electrically connected in a parallel configuration to permit the thermoelectric semiconductors to be powered by a single voltage source. The element may also be a sealed chamber that cools the fluid by using a Joule-Thompson orifice to create a phase change of a liquid to a gas inside the chamber. A temperature sensor monitors the temperature of the sealed chamber.  
           [0008]    Implementations may also include a sealing balloon positioned near the distal end of the elongated member that seals an external surface of the elongated member with a wall of a vessel. At least one hole may be provided in the elongated member proximal of the element to permit blood to enter the lumen. The temperature sensors may also comprise thermocouples.  
           [0009]    In another aspect, the invention features a method of performing an interventional procedure. The method includes inserting a guide catheter into an aorta and seating a distal end of the guide catheter in a coronary ostium. A lesion is treated to eliminate an impediment to blood flow through a vessel, the treatment permitting increased blood flow through the vessel. Cooled fluid is provided to the ischemic tissue region caused by the lesion.  
           [0010]    In embodiments, the lesion may be treated using an interventional catheter, which may be inserted through a lumen of a catheter that provides cooled fluid to the ischemic tissue region. Treatment of a lesion in a coronary artery and a coronary vein is provided. The fluid provided to the ischemic tissue region may be cooled as it flows through a lumen in a catheter. A temperature sensor may sense the temperature of the fluid provided to the ischemic tissue region.  
           [0011]    The cooled fluid may be provided either before or after physiological blood flow is restored. Further, the providing of cooled fluid may occur for a period of time after the treatment of the lesion. Cooled fluid may also be provided to an ischemic tissue region located in the brain or in the kidney. Cooled fluid may be delivered to a tissue area adjacent to the ischemic tissue region before the treatment of the lesion, and may continue to be provided to the tissue area adjacent to the ischemic tissue region during and after the treatment of the lesion. In applications where the cooled fluid is blood, the blood may enter the lumen through at least one hole in the catheter that is located proximal to a region of the catheter that cools the blood.  
           [0012]    In another aspect, the invention features a method of conducting an angioplasty procedure. The method includes inserting a dilation catheter into a lumen of the guide catheter and passing the dilation catheter through an opening at the distal end of the guide catheter into a coronary artery. An angioplasty procedure is performed by inserting a dilation catheter into a lumen of the guide catheter and passing the dilation catheter through an opening at the distal end of the guide catheter into a coronary artery. Cooled blood is delivered to an ischemic tissue region in the coronary artery through the guide catheter.  
           [0013]    In embodiments, the delivering of cooled blood may occur during the angioplasty procedure and may be delivered to the ischemic tissue region through the dilation catheter. The blood that is delivered to the ischemic tissue region may be cooled as it flows through the guide catheter. The guide catheter may also cool the fluid delivered through the dilation catheter. Further, the temperature of the cooled blood may be sensed by a temperature sensor.  
           [0014]    The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims.  
       
    
    
     DESCRIPTION OF DRAWINGS  
       [0015]    [0015]FIG. 1 is a perspective view of a catheter that cools fluid for delivery to a site internal to the body.  
         [0016]    [0016]FIG. 2A shows an alternative implementation of the catheter shown in FIG. 1.  
         [0017]    [0017]FIG. 2B shows an alternative implementation of the catheter shown in FIG. 1.  
         [0018]    [0018]FIG. 3 is a cross-sectional view, in a longitudinal plane, of a portion of the catheter near the catheter&#39;s distal end.  
         [0019]    [0019]FIG. 4 is a perspective view of a chilling section used for cooling fluid as it flows through the catheter. FIG. 5 is a side view of the chilling section shown in FIG. 4.  
         [0020]    [0020]FIG. 6 is a cross-sectional view, in a longitudinal plane, of a portion of the catheter containing a chilling section.  
         [0021]    [0021]FIG. 7 is a cross-sectional view of the catheter along the line  7 - 7  shown in FIG. 6.  
         [0022]    [0022]FIG. 8 is a cross-sectional view, in a longitudinal plane, of a portion of an alternative implementation of the catheter near the catheter&#39;s distal end.  
         [0023]    [0023]FIG. 9 is a cross-sectional view of the catheter along the line  9 - 9  show in FIG. 8.  
         [0024]    [0024]FIG. 10 is a cross-sectional view, in a longitudinal plane, of a portion of a dilation catheter near the catheter&#39;s distal end.  
         [0025]    [0025]FIG. 11 shows the connection of the proximal ends of a guide catheter and a dilation catheter and the apparatus that may be required when the guide catheter and dilation catheter are used together to perform percutaneous transluminal coronary angioplasty (PTCA).  
         [0026]    FIGS.  12 - 15  illustrate a method of performing a PTCA procedure to treat an ischemic tissue region caused by a lesion in a coronary artery.  
         [0027]    [0027]FIG. 16 illustrates a method of treating an ischemic tissue region caused by a lesion in a coronary artery.  
         [0028]    Like reference symbols in the various drawings indicate like elements. 
     
    
     DETAILED DESCRIPTION  
       [0029]    Referring to FIG. 1, a catheter  20  includes an elongate tubular shaft  22  with several chilling sections  26  in the shaft  22  near a distal end  34 . The catheter  20  may be used in conjunction with an interventional catheter (not shown) to repair a lesion in a coronary artery that has reduced or completely blocked the flow of oxygenated blood to a tissue region. The lack of oxygenated blood causes the tissue region to become ischemic. The catheter  20  may be used to provide cooled fluid, such as blood, to the ischemic tissue region. The chilling sections  26  cool fluid flowing through the tubular shaft  22 , and the cooled fluid exits the catheter&#39;s distal end  34 . Delivery of cooled fluid to the ischemic tissue region reduces injury associated with the reperfusion of blood to the region.  
         [0030]    The tubular shaft  22  is flexible to permit insertion into and through vessels in the body. In the implementation shown in FIG. 1, the shaft  22  has a U-shaped portion  30  near its distal end  34 . This shape permits the distal end  34  of the catheter  20  to be inserted into the aorta, via a femoral artery, and seated in a coronary ostium to provide access to a coronary artery, as will be described later. Although the FIG. 1 implementation has a shaft  22  shaped for use in the heart, the shaft  22  may be constructed in other shapes appropriate for other applications, such as insertion into the carotid artery, the coronary sinus via the right atria, or the renal artery via the aorta.  
         [0031]    The chilling sections  26  in this implementation are located near the catheter&#39;s distal end  34 , and more specifically in a distal leg  32  of the shaft&#39;s U-shaped portion  30 . The chilling sections  26  are cylindrically-shaped and are arranged in the shaft  22  such that the fluid flows longitudinally through the chilling sections  26  as the fluid flows through the shaft  22 . In the FIG. 1 implementation, there are six chilling sections  26  that are spaced a small distance apart from one another. By way of example, each chilling section  26  is about one to ten millimeters long, and the spacing between the sections  26  is approximately the same distance. The length and spacing of the chilling sections  26  may depend upon, for example, the desired flexibility of the portion of the shaft  22  containing the chilling sections  26  and the amount of cooling necessary for the specific application. Flexible tubing  28  is attached to the shaft  22  between the chilling sections  26  to reinforce the portion of the shaft  22  containing the chilling sections  26  as it flexes to maneuver the distal end  34  through vessels in the body.  
         [0032]    In other implementations, chilling sections  26  may be positioned elsewhere along the catheter&#39;s shaft  22 . For example, in a different implementation shown in FIG. 2A, the chilling sections  26  in the catheter  120  are positioned farther from the catheter&#39;s distal end  34 , but still nearer the distal end  34  than a proximal end of the shaft. Also, although there are six chilling sections  26  in the FIG. 1 implementation, there may be fewer or more chilling sections depending upon, for example, the volume of fluid being cooled, the location of the chilling sections  26  in the shaft  22 , and the amount of cooling necessary for the specific application. For example, the FIG. 2A implementation has eight chilling sections  26 .  
         [0033]    Referring again to FIG. 1, a balloon  24  on the shaft  22  may be inflated to provide a seal between the catheter&#39;s distal end  34  and, for example, a coronary ostium. When the distal end  34  is seated in the coronary ostium, cooled fluid can be supplied to the ischemic tissue region via the coronary artery. The seal prevents cooled fluid delivered to the ischemic tissue region from escaping the coronary artery and entering the aorta, and at the same time, prevents warm blood in the aorta from entering the coronary artery, as will be discussed later. The balloon  24  in the implementation of FIG. 1 has a cylindrical-shaped outer surface when inflated, but could be constructed to take on different shapes as necessary depending on the shape of the location where a seal is to be made. Further, the balloon  24  in other implementations may be placed at a different location along the shaft  22 , or may be omitted.  
         [0034]    An adapter  38  is attached to the shaft  22  at a proximal end  36  of the catheter  20 . The adapter  38  has a longitudinal opening  37  at the proximal end  36  to allow access to a lumen inside the shaft  22  (the lumen not being shown in FIG. 1). This internal lumen extends through the entire length of the shaft  22  to another longitudinal opening at the catheter&#39;s distal end  34 . This lumen will be referred to as an infusion lumen, because the lumen is used to deliver, or infuse, cooled fluid to sites inside the body, as will be described in more detail later. The adapter  38  also includes an attachment portion  40  to attach devices such as a haemostatic adapter or a Y-adapter. The adapter  38  also includes a grip  42  where a physician holds and torques the catheter  20  if desired. In other implementations, different adapters  38  may be placed on the proximal end  36  of the catheter  20 . For example, because the catheter  20  includes the sealing balloon  24 , the adapter  38  may also include a second opening, or port, to provide access to an inflation lumen that extends longitudinally from the catheter&#39;s proximal end  36  to the balloon  24 , as will be described in more detail later.  
         [0035]    In the interventional procedure briefly described earlier, the catheter  20  may be used as a guide catheter for an interventional catheter, such as a conventional dilation catheter used to perform a percutaneous transluminal coronary angioplasty (PTCA) (not shown in FIG. 1). Specifically, the dilation catheter may be inserted through the guide catheter&#39;s proximal opening  37  in the proximal end  36  and into the internal infusion lumen described earlier. The dilation catheter may then be extended through the shaft  22  so that the dilation catheter&#39;s balloon extends out of the distal end  34  of the shaft  22 . As such, the dilation balloon may be placed at a lesion to be treated. After treatment of the lesion and removal of the dilation catheter from the guide catheter  20 , fluid, such as blood, may be introduced into the infusion lumen through the proximal opening  37 . This fluid flows through the infusion lumen and past the chilling sections  26  where the fluid is cooled, and ultimately is delivered to the ischemic tissue region.  
         [0036]    In an alternative implementation shown in FIG. 2B, the catheter&#39;s shaft  22  may have one or a series of small holes  44  extending through the side of the shaft  22  and into the infusion lumen. The holes  44  may be located anywhere along the shaft  22  that is proximal of the chilling sections  26 . When the catheter  20  is placed in a blood vessel, blood will be forced into the infusion lumen through the holes  44 . Pressure exerted on the blood by the pumping of the heart forces the blood into the holes  44  and through the infusion lumen toward the distal end  34  of the catheter  20 , where the blood is cooled by the chilling sections  26  and then delivered to the ischemic tissue region.  
         [0037]    [0037]FIG. 3 shows a cross-sectional view, in a longitudinal plane, of a portion of the FIG. 1 catheter  20  near its distal end  34 . As shown in FIG. 3, the sealing balloon  24  is positioned over the shaft  22 , and around the shaft&#39;s entire circumference. Welds  50  secure and seal longitudinal ends of the balloon  24  to the shaft  22 , thus forming a sealed chamber  52  between the shaft  22  and the balloon  24 . An inflation lumen  54  extends through the shaft  22 , from the adapter  38  at the catheter&#39;s proximal end  36  (shown in FIG. 1) to, and into, the balloon chamber  52  (FIG. 3). The balloon chamber  52  may be inflated and deflated by providing and removing an inflation medium (gas or liquid) into the chamber  52 . As discussed previously, the balloon  24  provides a seal between the catheter shaft  22  and a vessel wall, for example, a coronary ostium. As such, the balloon  24  may be made of nylon, urethane, silicone, polyolefin copolymer, or other suitable materials. The materials of construction and dimensions of the balloon  24  may be different depending upon the application and the part of the body in which the balloon  24  is used.  
         [0038]    [0038]FIG. 3 also shows a temperature sensor  56 , located near the catheter&#39;s distal end  34 , to measure the temperature of exiting cooled fluid. In this implementation, the temperature sensor  56  is a thermocouple. The thermocouple  56  is made up of two conductive wires  60  of dissimilar material that are insulated from each other. The wires  60  extend longitudinally through the shaft  22 , from the catheter&#39;s adapter  38  (shown in FIG. 1) to a location near the catheter&#39;s distal end  34 . At this distal location, the conductive wires  60  are joined together to form a junction  62 . The junction  62  has surface area that extends into an inner wall  64  of the shaft  22 , such that the junction  62  is in thermal communication with fluid flowing through the infusion lumen  58  of the shaft  22 . When two dissimilar conductors are joined in this manner, an electromotive force (emf) is induced across the junction  62 , the magnitude of which induced emf varies as a function of the junction&#39;s temperature. The induced emf may be measured at the proximal ends of the conductive wires  62  (that is, outside the patient), and thus it is possible to determine the temperature of the fluid flowing through the infusion lumen  58  just before it exits the catheter&#39;s distal end  34 . If the fluid is not a desired temperature, then the chilling sections  26  may be adjusted to achieve the desired temperature, as will be described later. In other implementations, the temperature sensor  56  may be a thermistor or other suitable temperature sensing mechanisms. Further, the temperature sensor  56  may be placed at a different location in the shaft  22  to measure the temperature of the fluid flowing through the infusion lumen  58 .  
         [0039]    The infusion lumen  58 , part of which is shown in FIG. 3, extends from the catheter&#39;s proximal end  36  (FIG. 1) to its distal end  34 . The diameter of the lumen  58  depends on the application. For example, if blood is infused through the lumen  58 , the diameter of the lumen  58  needs to be large enough so that blood cells infused at the desired rate are not destroyed by the shear forces generated as they flow through the lumen  58 . The lumen diameter of various known guide catheters are sufficiently large to meet this requirement (e.g., 0.076″ to 0.110″). In addition, if it is intended that blood be infused through the lumen  58  during the same time that a dilation catheter is in the lumen  58  (for example, if cooled blood is infused during a PCTA procedure), the diameter of the catheter&#39;s lumen  58  may need to be, in some cases, larger than the lumen diameter of a conventional guide catheter. On the other hand, the maximum diameter of the lumen  58  is limited by the diameter of the body lumen into which the catheter  20  is to be inserted and the size of the incision through which the catheter  20  is inserted into the patient.  
         [0040]    FIGS.  4 - 6  show an example of a chilling section  26  that may be used in the catheters shown in FIGS. 1 and 2. In this implementation, the chilling section  26  is a thermoelectric cooler (TEC). The TEC  26  cools the fluid flowing through the catheter  20  by using a thermal energy process known as the Peltier effect. To use this process, a low voltage DC power source may be applied to a thermoelectric module to move heat through the module from one side to the other, as will be described in detail later. FIG. 4 is a perspective view of the TEC  26 . FIG. 5 is a side view of the TEC  26  that provides a simplified depiction of the thermoelectric semiconductor element pairs  102  that cool the fluid flowing through the catheter  20 . FIG. 6 shows a cross-sectional view, in a longitudinal plane, of a portion of the catheter  20  containing the TEC  26  shown in FIGS. 4 and 5.  
         [0041]    Referring to FIG. 4, the TEC  26  includes a first and second module  70  and  72 , respectively. When the first and second modules  70  and  72  are placed together, they form a cylinder with lumen  58  through which fluid may flow. To form this cylinder-shaped structure, both the first and second modules  70  and  72  are in the shape of a half-cylinder, where the cylinder is split longitudinally into two equally-sized sections. The longitudinal edges of the first and second modules  70  and  72  are separated by small gaps  91   a  and  91   b . The TEC  26  in this implementation may be, for example, one to ten millimeters long. Alternatively, the TEC  26  could be comprised of narrow flat modules or other shapes suitable for use in the catheter  20 .  
         [0042]    The first module  70  of the TEC  26  is connected to wires  74  and  76  at the first module&#39;s proximal end  90 , and connected to wires  82  and  84  at the first module&#39;s distal end  92 . In this implementation, wires  74  and  76  extend longitudinally through the shaft of the catheter toward the catheter&#39;s proximal end. The wires  74  and  76  may be connected to the first module  70  of another TEC  26  in the catheter located proximal to the TEC  26  shown in FIG. 6 (the connection not being shown in FIG. 6). If the TEC  26  is the most proximal chilling section in the shaft, the wires  74  and  76  extend longitudinally through the shaft to the catheter&#39;s proximal end for access outside of the patient. The wires  82  and  84  extend longitudinally through the shaft toward the catheter&#39;s distal end and may be connected to the first module  70  of another TEC  26  located distal to the chilling section shown in FIG. 6.  
         [0043]    The second module  72  of the TEC  26  is similarly connected to wires  78  and  80  at the first module&#39;s proximal end  90 , and connected to wires  86  and  88  at the first module&#39;s distal end  92 . The wires  78 ,  80 ,  86 , and  88  extend through the shaft and connect to the second modules  72  of the various TECs  26  in the catheter in the same manner as described for the first modules  70 .  
         [0044]    Referring to FIG. 5, the wires  74 ,  76 ,  82  and  84  are connected to the first module  70  at connection points  94 . Similarly, the wires  78 ,  80 ,  86 , and  88  are connected to the second module  72  at connections points  96 . The first and second modules  70  and  72  include a number of thermoelectric semiconductor element pairs  102 . The element pairs  102  in the first module  70  are powered by applying a DC voltage to the wires  74  and  76 . Similarly, the element pairs  102  in the second module  72  are powered by applying a DC voltage to the wire  78  and  80 . The element pairs  102  within the first and second modules  70  and  72  are arranged in a parallel configuration. Thus, the same DC voltage may be applied to all of the element pairs  102  in each of the modules  70  and  72 . The wires  74  and  76  are connected to the wires  82  and  84  through the first module  70 . This connection allows the DC voltage applied to the first module  70  to be applied to all of the first modules  70  in the catheter  20 . As a result, all of the element pairs  102  in the first modules may be controlled with a single voltage source. Similarly, the wires  78  and  80  are connected to wires  86  and  88 , which allows all of the element pairs  102  in the second modules  72  to be powered by a single voltage source. In other implementations, the modules  70  and  72  may be arranged in a series configuration. Further, the element pairs  102  may also be arranged in a series configuration within the modules  70  and  72 .  
         [0045]    Referring to FIG. 6, the element pairs  102  in the TEC are spaced throughout the first and second modules  70  and  72  of the TEC  26  and are packaged within an electrical insulator  104 . In this implementation, the element pairs  102  include an n-type semiconductor and a p-type semiconductor electrically connected in series (the semiconductors not being shown). However, the semiconductors may be replaced with other suitable materials. The conductors are arranged in a substrate that electrically insulates the semiconductors within the element pairs  102  from heat sinks attached to the substrate on two sides of the element pairs  102  (the substrate and heat sinks not being shown). The element pairs  102  are arranged so that one heat sink is adjacent to an internal surface  108  of the first and second modules  70  and  72 , and the other heat sink is adjacent to an external surface  106 .  
         [0046]    Applying the DC voltage to the modules  70  and  72  causes a current to pass through the n-type and p-type semiconductors within the element pairs  102 . The current causes heat to be drawn from the heat sink near the internal surface  108  to the heat sink near the external surface  106 . Through this process, the internal surface  108  is cooled, and at the same time, the external surface  106  is heated. By cooling the internal surface  108  of the first and second modules  70  and  72 , fluid passing through the lumen  58  may also be cooled.  
         [0047]    The cooling of the internal surfaces  108  may be adjusted by changing the voltage applied to the modules  70  and  72 , which changes the current flowing element pairs  102 . For example, if the current is increased, the cooling of the TEC  26  may be increased, which in turn further decreases the temperature of the fluid flowing through the lumen  58 . Similarly, decreasing the current flowing through the element pairs  102  decreases the cooling of the TEC  26 .  
         [0048]    A flexible tubing  28  may be attached to the area of the shaft  22  proximal to the TEC  26  at a longitudinal end by welds  110 . Alternatively, the flexible tubing  28  may be attached to the shaft  22  like a sleeve over the entire area of the shaft  22  containing the TECs  26 . The flexible tubing  28  may be constructed of a polymer or a metal braid with polymer encapsulation depending upon the longitudinal length of the TEC  26 . As described earlier, the flexible tubing  28  reinforces the area of the shaft  22  between the rigid TEC  26  as that area is flexed to maneuver the distal end of the catheter through vessels in the body. In implementations where the chilling sections  26  are flexible, the flexible tubing  28  may be omitted.  
         [0049]    [0049]FIG. 7 shows a cross-sectional view of the catheter shaft  22  at line  7 - 7  of FIG. 6 looking toward the chilling section  26 . In the implementation shown, the shaft  22  includes three primary layers  112 ,  114 , and  118 . An inner layer  112  encloses the infusion lumen  58  within, and is comprised of PTFE or FEP, as is conventional. A middle layer  114  encloses the inner layer  112  and is comprised of braided metal wires constructed of stainless steel or tungsten. An outer layer  118  enclosing the middle layer  116  is constructed of a polymer, such as nylon. In other implementations, different materials may be used to construct the layers  112 ,  114 , and  118  of the catheter shaft  22 , such as urethane or tantalum wire.  
         [0050]    Also shown in FIG. 7 is the layer  28  of flexible tubing shown in FIG. 6. This flexible tubing layer  28  surrounds the shaft&#39;s outer layer  118  between the chilling sections  26 . Dashed lines have also been added to the cross-section of FIG. 7 to indicate the location of the chilling sections  26  in the shaft  22  of the catheter with respect to the layers  112 ,  114 , and  118 . In this implementation, the first and second modules  70  and  72  are positioned between the shaft&#39;s inner layer  112  and its outer layer  118  such that the internal surfaces  108  of the first and second modules  70  and  72  are in thermal contact with the fluid flowing through the infusion lumen  58 .  
         [0051]    The wires  82 ,  84 ,  86 , and  88  extend through the catheter shaft  22  in the layer  118  and are held in place by wire holders  116 . In addition, the thermocouple wires  60  and the inflation lumen  54  extend from the distal end to proximal end of the catheter shaft  22  through layer  118  near the outer edge  122 . The thermocouple wires  60  pass through the gap  91   a  between the first and second modules  70  and  72 . Similarly, the inflation lumen  54  passes through the gap  91   b .  
         [0052]    [0052]FIG. 8 shows a cross-sectional view, in a longitudinal plane, of a distal part of another catheter  220  that uses the physical process known as the Joule-Thompson effect to cool the fluid as it flows through the catheter  200 . To use this process, a fluid is introduced into the thermo cooler chamber  148  and is allowed to change phase to a gas, which reduces the temperature of the thermo cooler chamber  148  and the fluid flowing through the catheter in thermal contact with the chamber  148 . Like the catheter  20  described previously, the catheter  220  may be used in conjunction with an interventional catheter, such as a dilation catheter (not shown), to provide cooled fluid to an ischemic tissue region.  
         [0053]    The catheter  220  includes a thermo cooler chamber  148  extending around the circumference of the catheter  220 , an infusion tube  144 , and an exhaust tube  146 . The exhaust tube  146  removes the contents of the area  148  to maintain an ambient pressure in chamber  148 . A highly-pressurized fluid, such as CO 2 , N 2 O, N 2 , or He, enters the chamber  148  via the infusion tube  144  and an orifice  152 . As the fluid changes phase from liquid to gas in the thermo cooler chamber  148 , energy in the form of heat is pulled from the surrounding area, which cools the thermo cooler chamber  148  and the fluid flowing through the infusion lumen  158  of the catheter  220 .  
         [0054]    The thermo cooler chamber  148  may be, for example, one to 30 centimeters in length longitudinally and approximately 0.5 to three millimeters in width. These dimensions may be increased or decreased depending on factors, such as the amount of cooling desired and the pressure of the gas to be introduced to the thermo cooler chamber  148 . The walls of the thermo cooler chamber  148  are noncompliant but flexible to accommodate the pressure changes caused by the introduction and removal of gas into the chamber  148 . In this implementation, the walls are made of PET, but could be constructed of any material with similar properties, such as nylon. Further, the thermo cooler chamber  148  could be placed at different locations in the shaft  222  to cool the fluid flowing through the infusion lumen  158 . The cooler chamber  148  may be coated with a polymer to insulate its exterior from the heat of the body (not shown). Alternatively, a layer of CO 2  may be introduced into a separate exterior pocket surrounding the cooler chamber  148  to provide insulation (not shown).  
         [0055]    The exhaust tube  146  extends through the catheter shaft  222  from the thermo cooler chamber  148  to the proximal end of the catheter  220  (not shown). The infusion tube  144  also extends through the catheter shaft  222  from the thermo cooler chamber  148  to the proximal end of the catheter  220 . The distal end of the infusion tube  144  may include one or more orifices  152  to control the flow of fluid into the thermo cooler chamber  148 . In other implementations, the infusion tube  144  may be shaped differently to direct the flow of the fluid to the chamber  148 .  
         [0056]    A temperature sensor  164  is located near the thermo cooler chamber  148  and monitors the temperature of the chamber  148 . FIG. 8 also shows a temperature sensor  156  located near the catheter&#39;s distal end  134  to measure the temperature of cooled fluid as it exits the infusion lumen  158 . In this implementation, the temperature sensors  156  and  164  are thermocouples. As described previously, the thermocouples  156  and  164  are made up of two conductive wires of dissimilar material and insulated from each other. The conductive wires are joined together to form junctions  162  and  166 . The junction  162  is in thermal contact with the fluid flowing through the infusion lumen  158  of the shaft  222 , and the junction  166  is in thermal contact with the expanding gas in the thermo cooler chamber  148 . In other implementations, temperature sensors other than a thermocouple may be used, such as thermistors or other suitable temperature sensing mechanisms.  
         [0057]    [0057]FIG. 9 shows a cross-sectional view of the catheter shaft  222  at line  9 - 9  of FIG. 8 looking away from the thermo cooler chamber. In the implementation shown, the shaft  222  includes three primary layers  212 ,  214 , and  216 . The inner layer  212  encloses the infusion lumen  158  within, and is comprised of PTFE or FEP as is conventional. A middle layer  214  encloses the inner layer and is comprised of braided metal wires constructed of stainless steel or tungsten. An outer layer  216  encloses the middle layer  214  and is constructed of polymer. In other implementations, different materials may be used to construct the layers  212 ,  214 , and  216  of the catheter, such as urethane or tantalum wire.  
         [0058]    The wires  160  for the thermocouple  156 , the wires  168  for thermocouple  164 , the infusion tube  144 , and the exhaust tube  146  extend longitudinally through the catheter shaft  222  to the proximal end of the catheter (not shown) in the layer  216 . In this implementation, the wires  160  attached to the thermocouple  156  are positioned in layer  216  near the infusion tube  144 . Similarly, the thermocouple wires  168  attached to the temperature sensor  164  are located near the exhaust tube  146  in a position  180  degrees from the thermocouple wires  160  and infusion tube  144 . In other implementations, the thermocouple wires  160  and  168 , the infusion tube  144 , and the exhaust tube  146  may be positioned in a different layer of the catheter shaft  222 , or in a different position within the layer  216  shown in FIG. 9.  
         [0059]    [0059]FIG. 10 shows a cross-sectional view, in a longitudinal plane, of a portion of a dilation catheter  250  near the catheter&#39;s distal end  252  that contains a temperature sensor  256 . The catheter  250  may used in conjunction with a guide catheter, such as catheters  20 ,  120 , or  220  to perform an interventional procedure, such as a PTCA procedure, to repair a lesion in a coronary artery that has reduced or completely blocked the flow of oxygenated blood to a tissue region. The catheter  250  may be inserted into and through the guide catheter to access the lesion in the coronary artery. The distal end  252  may then be placed through the lesion to provide cooled fluid, such as a saline, to the ischemic tissue region. The delivery of cooled fluid may continue until the dilation balloon  254  is inflated, the lesion has been repaired, and the catheter  250  has been removed from the coronary artery.  
         [0060]    The temperature sensor  256  located near the catheter&#39;s distal end  152  measures the temperature of the fluid exiting the catheter for delivery to the tissue region. In this implementation, the temperature sensor  256  is a thermocouple. As described previously, the thermocouple  256  includes a junction  260  that has a surface area in thermal contact with fluid flowing through the infusion lumen  258  of the catheter  250 . If the fluid is not a desired temperature (for example, 20 degrees Celsius in the case of cooling of ischemic tissue), then the temperature may be adjusted as desired. In other implementations, temperature sensors other than a thermocouple may be used, such as thermistor or other suitable temperature sensing mechanisms. Further, the temperature sensor  256  may be placed at a different location in the catheter  250  to measure the temperature of the fluid flowing through the infusion lumen  258 .  
         [0061]    [0061]FIG. 11 shows various external devices that may be utilized when a conventional guide catheter  300  and an interventional catheter, such as a dilation catheter  302 , are used together to deliver cool fluid to a site internal to the body. FIG. 11 also illustrates the configuration of the various adapters  304 ,  306 , and  308  with respect to each other and the external devices in the system.  
         [0062]    In a PTCA procedure, for example, a conventional Y-adapter  306  is attached to the adapter  304  at the proximal end of the conventional guide catheter  300 . The Y-adapter  306  provides access to the infusion lumen of the guide catheter  300  through ports  310  and  312 . The dilation catheter  302  is inserted into the infusion lumen of the guide catheter  300  through the port  312 . The dilation catheter  302  may then be extended into and through the guide catheter  300  for access to the lesion that has reduced the blood flow in the coronary artery. In the configuration shown, a cooled fluid may be introduced to the infusion lumen of the guide catheter  300  through the port  310  for delivery to the ischemic tissue region.  
         [0063]    The adapter  308  on the proximal end of the dilation catheter  302  includes two ports  314  and  316 . The port  314  provides access to the dilation balloon on the dilation catheter  302 . The dilation balloon may be inflated and deflated by providing and removing an inflation medium  314 . Another port  316  provides access to the infusion lumen of the dilation catheter  302  so that cooled fluid may be delivered to a site internal to the body, for example, an ischemic tissue region.  
         [0064]    In this implementation, the cooled fluid delivered by the dilation catheter  302  is a saline solution  320 . The saline solution  320  may contain antioxidants or other vascular agents such as nitric oxide, lidocaine, nitroglycerine, insulin, adenosine, ATP, heat shock proteins, beta blockers, modifiers of calcium channel, modifiers of potassium channel, or other enzymes or metabolism modifiers. Modifiers of inflammatory response, modifiers of transmembrane transport, modifiers of lactic acid concentration, or other substances may also be included. The saline solution  320  could also contain delta opiod peptides (e.g. D-Ala2-Leu5-enkephalin DADLE) or other hibernation induction trigger agents. In other implementations, the saline solution  320  could be replaced with blood, a blood substitute, or a mixture of both. Further, the type of fluid provided to the ischemic tissue region through the dilation catheter  302  may be changed throughout the PTCA procedure.  
         [0065]    The saline solution may be urged through the infusion lumen of the dilation catheter  302  by a conventional pump  322 . For example, a positive displacement pump may be used to provide the pressure necessary to urge the saline solution  320  through the narrow infusion lumen of the dilation catheter  302 . In other implementations the pump  322  may be replaced with a raised bag containing the saline solution  320  with an inflatable pressure cuff to control the infusion rate of the solution  320 . A conventional infusion monitor  324  monitors the pressure and flow rate of the saline solution  320  through the infusion lumen of the dilation catheter  302 . In the PTCA example, the saline solution  320  flows through the infusion lumen of the dilation catheter  302  at a rate of ten to 50 ml/min. The flow rate and pressure may be increased or decreased as required by different applications.  
         [0066]    A heat exchanger may be used to cool the saline solution  320 . A temperature monitor  328  may also be coupled to a temperature sensor, as described previously, to monitor the temperature of the solution  320  as it exits the distal end of the dilation catheter  302 . Based on the feedback provided by the temperature monitor  328 , the heat exchanger  326  may be adjusted to increase or decrease the temperature of the solution  320  to further reduce the tissue injury. The rate of tissue cooling may be controlled by adjusting either the infusion temperature, the infusion rate, or both. A filter  330  filters the solution  320  before it is introduced into the infusion lumen of the dilation catheter  302  for delivery.  
         [0067]    The guide catheter  300  may also deliver a cooled fluid to a site internal to the body. In the PTCA example, the fluid delivered to the ischemic tissue is typically cooled blood  332 . The blood  332  may be taken directly from the patient or may be from an external source. In the PTCA application and other applications in which the guide catheter  300  may be used, the blood  332  may be replaced with blood substitutes or saline solutions containing any of the agents and modifiers discussed previously.  
         [0068]    In the PTCA example, a pump  334  urges the blood  332  through the infusion lumen of the guide catheter  300 . For example, a roller pump may be used to provide blood to a coronary artery after a lesion has been repaired at a pressure normally applied by the heart. In other applications, other pumps may be used to increase or decrease the pressure of the fluid flowing through the infusion lumen as necessary. An infusion monitor  336  monitors the pressure and flow rate of the blood moving through the infusion lumen of the catheter  300 .  
         [0069]    A conventional heat exchanger  338  may be used to cool the blood  332  delivered to the ischemic region to a desired temperature, such as  33  degrees Celsius. A temperature monitor  340  may also be included to monitor the temperature of the blood  332  exiting the infusion lumen of the guide catheter  302 . As described earlier, the heat exchanger  338  may be adjusted to increase or decrease the temperature of the solution  332  to minimize the tissue injury associated with an ischemic event. Further, the tissue cooling may be controlled by adjusting the flow rate of the solution  332  through the catheter  300 . A filter  342  filters the blood  332  before it is introduced to the infusion lumen for delivery.  
         [0070]    In an implementation in which the conventional guide catheter  300  is replaced with the guide catheter  20 ,  120 , or  220  described previously, the blood  332  may be cooled inside the catheter, which eliminates the need for the heat exchanger  338 . Further, in the implementation where the blood is introduced into the infusion lumen of the catheter  20  through small holes along the catheter shaft, the blood supply  332 , the pump  334 , the infusion monitor  336 , and the filter  342  may not be needed. The only external apparatus that may be required in such an implementation is a temperature monitor attached to the temperature sensor to monitor the temperature of the blood exiting the infusion lumen and a device to control the cooling of the chilling sections in the catheter shaft. In an implementation in which the guide catheter includes a sealing balloon, another port on the proximal end of the catheter may be required to provide and remove an inflation medium to inflate and deflate the sealing balloon.  
         [0071]    Further, in an implementation where guide catheter  300  is replaced with the guide catheter  20 ,  120 , or  220 , the fluid flowing though the dilation catheter  302  may be cooled by the guide catheters  20 ,  120 , or  200 . In an implementation such as this, the heat exchanger  326  may not be needed.  
         [0072]    FIGS.  12 - 15  illustrate a method of performing a PTCA procedure to repair a lesion  350  in a coronary artery  354  that has reduced or completely blocked the flow of oxygenated blood to a tissue region  366  causing the tissue region to become ischemic. This method may be referred to as an “antegrade method” of performing a PTCA because the lesion  350  in the coronary artery  354  is accessed in the same direction as normal blood flow, i.e., from the aorta  356 .  
         [0073]    [0073]FIG. 12 shows a distal end  364  of the dilation catheter  302  extended through an opening in the distal end  358  of the guide catheter  300 , which is seated in the coronary ostium  360 . In the implementation shown, the guide catheter  300  includes a sealing balloon  362  that is inflated to provide a seal between the guide catheter&#39;s distal end  358  and the wall of the coronary artery  354 . Once the distal end  358  of the guide catheter  300  is seated in the coronary ostium  360 , cooled blood  332  may be delivered to the coronary artery  354 , despite the fact that the coronary artery  354  is blocked by the lesion  350 . The cooled blood provided by the guide catheter  300  may cool the tissue areas surrounding the ischemic tissue region  366  (shown in FIG. 13) via branching artery  355 , which may provide a cooling effect on the ischemic tissue. To repair the lesion  350 , the physician directs the distal end  364  of the dilation catheter  302  through the guide catheter  300  along the guide wire  352  into the coronary artery  354  and to a position distal to the lesion  350  as shown in FIG. 13.  
         [0074]    Referring to FIG. 13, the dilation catheter&#39;s distal end  364  is positioned distal to the lesion  350  such that the catheter  302  may provide cooled fluid, such as the saline solution  320 , to the ischemic tissue region  366 . As described earlier, the saline solution  320  provided to the ischemic tissue region by the dilation catheter  302  may contain any number of chemical agents. Further, the contents of the saline solution  320  may be varied throughout the procedure. For example, a first solution may be used to provide an initial flush of the ischemic tissue region to rid the area of harmful free radicals or metabolic products that build up during the ischemic period. Once the initial flush is complete, a second solution may be provided to continue the cooling process. Additional solutions may be used throughout the procedure as desired.  
         [0075]    As the dilation catheter  302  is providing cooled fluid to the ischemic tissue region  366 , the physician may inflate the dilation balloon  368  to repair the lesion  350 . During the repair of the lesion  350 , the dilation catheter may continue to deliver the cooled solution  320  to the ischemic tissue region  366 . After the lesion  350  is repaired, the physician will then deflate the balloon  368  and remove the dilation catheter  302  from the coronary artery  354 . The guide catheter  300  may continue to provide cooled blood  332  to the ischemic tissue region  366  for a period of time, for example twenty minutes, after the lesion  350  has been repaired, as shown in FIG. 14.  
         [0076]    [0076]FIG. 15 shows the distal end of a subselective catheter  400  extending through an opening in the distal end  358  of the guide catheter  300 . In this example, the distal end  358  of the catheter  300  is pulled back from the coronary ostium  360 . The removal of the seal at the ostium  360  permits physiological blood flow to be restored, as indicated by the arrows. The catheter  400  may be used to infuse cooled blood or a cooled solution into a specific tissue region, such as the ischemic tissue region  366 .  
         [0077]    [0077]FIG. 16 shows a method of treating an ischemic tissue region caused by a lesion  350  that has reduced or completely blocked the flow of blood through the artery  354 . The method in FIG. 16 may be referred to as a retrograde method of cooling an ischemic tissue region because the ischemic tissue region is accessed through a coronary vein  378  in a direction opposite normal blood flow.  
         [0078]    A distal end  380  of a conventional sealing catheter  374  is extended through an opening in the distal end  358  of a conventional guide catheter  300 , which is inserted into the coronary sinus  370 . The distal end  380  of the sealing catheter  374  is positioned in the coronary vein  378  to provide a cooled solution to the capillary bed  372  for treatment of the ischemic tissue region  366 . A sealing balloon  376  located near the distal end  380  may be inflated to prevent the cooled solution  320  provided by the sealing catheter  374  from flowing out of the coronary vein  378  and into the coronary sinus  370 .  
         [0079]    The cooled solution provided during the retrograde cooling method may contain arterial blood or an oxygen-carrying blood substitute. Alternatively, the cooled solution may contain any number of the chemical agents discussed previously. Further, the cooled solution may be changed throughout the procedure.  
         [0080]    The retrograde cooling method shown in FIG. 16 may be used to cool an ischemic tissue region  366  in conjunction with the antegrade cooling method described previously to provide a more focused therapy. For example, the retrograde method could be used to target the ischemic tissue region  366 , while the antegrade cooling method could be used to cool surrounding tissue. The methods could also be used in a sequential fashion. For example, the retrograde method could be used to initially cool the tissue prior to reperfusion and the antegrade method could be used at the time of reperfusion to give an added flush of the ischemic tissue region with the cooled solution to remove metabolic products that build up in the region during the ischemic event.  
         [0081]    A number of implementations have been described. Nevertheless, it will be understood that various modifications may be made. For example, the devices and methods described may be used to cool other tissue, such as the brain, kidneys, and other organs in the body. Accordingly, other implementations are within the scope of the following claims.