Methods and systems for treating ischemia

Methods for treating total and partial occlusions employ a perfusion conduit which is penetrated through the occlusive material. Oxygenated blood or other medium is then perfused through the conduit to maintain oxygenation and relieve ischemia in tissue distal to the occlusion. Optionally, the occlusion may be treated while perfusion is maintained, typically by introducing a thrombolytic or other agent into the occlusive material using the perfusion conduit. Such methods are particularly suitable for treating acute stroke to prevent irreversible damage to the cerebral tissue.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention relates generally to medical devices and methods. 
More particularly, the present invention relates to catheters, systems, 
kits, and methods for treating ischemia, such as intracerebral ischemia 
associated with stroke. 
Hemodynamically significant restriction of arterial blood flow can lead to 
oxygen deprivation in tissue, referred to as ischemia, and can quickly 
lead to cell death and organ dysfunction. The brain is the organ most 
sensitive to ischemia, followed by the heart, the abdominal organs, and 
the extremities. The brain will usually not tolerate ischemia for very 
long without massive neuron death (stroke). When treating ischemic events 
in the brain, it is imperative to restore blood flow quickly and safely. 
The most common causes of acute arterial ischemia in the cerebrovasculature 
are thrombosis and embolus. Thrombus usually forms at the site of a 
pre-existing atherosclerotic lesion and can cause an acute occlusion. 
Atherosclerosis can occur at any location within the arteries that deliver 
blood from the heart to the brain, but the most common locations of 
significant atherosclerosis are the cervical carotid artery at the carotid 
bifurcation, the proximal middle cerebral artery, and the vertebrobasilar 
arterial system. Clinically significant atherosclerosis also can occur in 
other intracerebral vessels. 
Emboli are formed when previously stable thrombus or atheroma is released 
into the blood stream and becomes lodged in smaller blood vessels. Emboli 
can originate from atherosclerotic lesions and from within the cardiac 
chambers. They can cause acute obstructions of blood vessels, resulting in 
tissue hypoxia and neuron death. Further obstruction can also occur 
distally to the embolus due to secondary inflammatory responses and other 
reactions. Transient ischemic attacks (TIA's) occur with temporary and 
intermittent obstructions, allowing for neuron recovery. Stroke occurs 
with longer term obstruction to blood flow. 
Traditional therapy of acute stroke has been limited to the delivery of 
supportive measures. Newer treatments for stroke attempt to relieve or 
bypass vessel occlusion before neuron death occurs. In the life 
threatening emergency of acute stroke, there is a time-limited window of 
opportunity for treatment after the onset of symptoms. After this 
treatment window has closed, there is minimal opportunity for recovery of 
neuronal function. Furthermore, restoring blood perfusion late in the 
therapeutic window can cause cerebral hemorrhage or edema and progression 
of symptoms, referred to as the "reperfusion syndrome." For this reason, 
recent emphasis has been placed on the early treatment of patients, 
usually within six hours of the onset of symptoms, and on relieving the 
obstruction emergently. 
A number of techniques have been proposed which employ site-specific 
administration of thrombolytic drugs and/or mechanical means, laser or 
ultrasound energy sources to remove thrombus. Angioplasty, atherectomy and 
stent placement are employed to relieve atherosclerotic stenoses. These 
methods all require positioning catheter based devices at or near the site 
of the arterial obstruction. The primary objective is to restore blood 
flow as quickly as possible. Such devices, however, require significant 
time to position and use. There are also risks of damaging the obstructed 
artery, of dislodging and embolizing blood thrombus or atherosclerotic 
plaque, of inducing intracerebral hemorrhage or other serious 
complications. Directed thrombolysis using currently available catheters 
and guidewires often takes many hours to complete. While excellent 
technical results are feasible, many patients cannot tolerate the wait and 
their condition can deteriorate during the procedure. Surgical bypass does 
not work as well as standard medical therapy in preventing stroke 
recurrence and is only rarely performed. 
New classes of "neuroprotectant" agents and "angiogenesis promoters" have 
been proposed. These drugs may extend the effective therapeutic window for 
stroke therapy and permit better long term outcomes. Their use, however, 
may require novel delivery systems and often require that the patient be 
stabilized and ischemia relieved in order to obtain a lasting clinical 
improvement. 
For these reasons, it would be desirable to provide improved methods and 
apparatus for treating acute ischemic conditions, particularly stroke. It 
would be further desirable if such methods and apparatus were also useful 
for treating chronic ischemia in other portions of a patient's 
vasculature, including the coronary vasculature and the peripheral and 
mesenteric vasculature. The methods and apparatus should be capable of 
rapidly reestablishing blood flow at a rate sufficient to relieve ischemia 
distal to the occlusion, and would ideally (but not necessarily) be 
adaptable for use both in an emergency situation (i.e., outside the 
hospital) as well as within a hospital environment. The methods and 
apparatus should provide for control over the rate of blood flow and/or 
cessation of blood flow to the ischemic region in order to avoid 
reperfusion injury. In addition to relieving ischemia, the methods and 
devices of the present invention will preferably further provide access 
and support for performing other therapeutic interventions to treat the 
occlusion, including both drug interventions and mechanical interventions. 
Additionally, the methods and devices should be adaptable to use access 
routes of a type which are familiar to interventionalists so as to permit 
rapid and wide spread adoption. At least some of these objectives will be 
met by different aspects of the present invention. 
2. Description of the Background Art 
U.S. Pat. No. 5,149,321 describes an emergency system for infusing an 
oxygenated medium into the cerebral vasculature in patients following a 
heart attack. Active perfusion through coronary angioplasty catheters is 
described in a number of patents and published applications, including 
U.S. Pat. Nos. 5,106,363; 5,158,540; 5,186,713; and 5,407,424; Canadian 
Patent 1,322,315; and WO 97/19713. The latter describes perfusion of an 
oxygenated medium through a guidewire. Perfusion and/or infusion catheters 
and systems are described in a number of patents, including U.S. Pat. Nos. 
5,584,804; 5,090,960; 4,611,094; 4,666,426; 4,921,483; 5,643,228; 
5,451,207; 5,425,723; 5,462,523; 5,531,715; 5,403,274; 5,184,627; 
5,066,282; 4,850,969; 4,804,358; 4,468,216; and WO 92/20398. U.S. Pat. No. 
5,090,960 describes a passive perfusion catheter having spaced-apart 
balloons and a suction tube for recirculating a thrombolytic agent. 
SUMMARY OF THE INVENTION 
The present invention provides methods, apparatus, and kits for treating 
patients suffering from ischemia resulting from the partial or total 
obstruction of a blood vessel. Usually, the obstructions will be 
high-grade blockages, e.g., those which result in greater than 75% flow 
reduction, but in some instances they may be of a lower grade, e.g., 
ulcerated lesions. As used hereinafter, the terms "obstruction," 
"occlusion," and "blockage" will be used generally interchangeably and 
will refer to both total obstructions where substantially all flow through 
a blood vessel is stopped as well as to partial obstructions where flow 
through the blood vessel remains, although at a lower rate than if the 
obstruction were absent. 
Preferred use of the present invention is for the treatment of patients 
suffering from acute stroke resulting from a sudden, catastrophic blockage 
of a cerebral artery. The present invention, however, will also be useful 
for treating acute blockages in other portions of the vasculature as well 
as for treating chronic occlusions in the cerebral, cardiac, peripheral, 
mesenteric, and other vasculature. Optionally, the methods of the present 
invention may be used to facilitate dissolving or removing the primary 
obstruction responsible for the ischemia, e.g., by drug delivery, 
mechanical intervention, or the like, while perfusion is maintained to 
relieve the ischemia. 
Methods according to the present invention comprise penetrating a perfusion 
conduit through the blockage and subsequently pumping an oxygenated medium 
through the conduit at a rate or pressure sufficient to relieve ischemia 
downstream from the blockage. Usually, the oxygenated medium is blood, 
more usually being blood obtained from the patient being treated. In some 
instances, however, it will be possible to use other oxygenated media, 
such as perfluorocarbons or other synthetic blood substitutes. In a 
preferred aspect of the present invention, the pumping step comprises 
drawing oxygenated blood from the patient, and pumping the blood back 
through the conduit at a controlled pressure and/or rate, typically a 
pressure within the range from 50 mmHg to 300 mmHg, preferably at a mean 
arterial pressure in the range from 50 mmHg to 150 mmHg, and at a rate in 
the range from 30 cc/min to 360 cc/min, usually from 30 cc/min to 240 
cc/min, and preferably from 30 cc/min to 180 cc/min, for the cerebral 
vasculature. Usually, pressure and flow rate will both be monitored. 
Pressure is preferably monitored using one or more pressure sensing 
element(s) on the catheter which may be disposed distal and/or proximal to 
the obstruction where the blood or other oxygenated medium is being 
released. Flow rate is easily monitored on the pumping unit in a 
conventional manner. Conveniently, the blood may be withdrawn through a 
sheath which is used for percutaneously introducing the perfusion conduit. 
It will usually be desirable to control the pressure and/or flow rate of 
the oxygenated medium being delivered distally to the occlusion. Usually, 
the delivered pressure of the oxygenated medium should be maintained below 
the local peak systolic pressure and/or mean arterial blood pressure of 
the vasculature at a location proximal to the occlusion. It will generally 
be undesirable to expose the vasculature distal to the occlusion to a 
pressure above that to which it has been exposed prior to the occlusion. 
Pressure control of the delivered oxygenated medium will, of course, 
depend on the manner in which the medium is being delivered. In instances 
where the oxygenated medium is blood which is being passively perfused 
past the occlusion, the delivered pressure will be limited to well below 
the inlet pressure, which is typically the local pressure in the artery 
immediately proximal to the occlusion. Pressure control may be necessary, 
however, when the oxygenated medium or blood is being actively pumped. In 
such cases, the pump may have a generally continuous (non-pulsatile) 
output or in some cases may have a pulsatile output, e.g., being pulsed to 
mimic coronary output. In the case of a continuous pump output, it is 
preferred that the pressure being released distally of the occlusion be 
maintained below the mean arterial pressure immediately distal to the 
occlusion, usually being below 150 mmHg, often being below 100 mmHg. In 
the case of a pulsatile pump output, the peak pressure should be 
maintained below the peak systolic pressure upstream of the occlusion, 
typically being below 200 mmHg, usually being below 150 mmHg. Control may 
be based on the measured pressure proximal of the occlusion or could be 
based on an average value of the mean arterial pressure or peak systolic 
pressure expected for most patients. 
In some instances, it will be desirable to initiate the flow of blood or 
other oxygenated medium slowly and allow the flow rate and pressure to 
achieve their target values over time. For example, when actively pumping 
the oxygenated medium, the pumping rate can be initiated at a very low 
level, typically less than 30 cc/min, often less than 10 cc/min, and 
sometimes beginning at essentially no flow and can then be increased in a 
linear or non-linear manner until reaching the target value. Rates of 
increase can be from 1 cc/min/min to 360 cc/min/min, usually being from 5 
cc/min/min to 100 cc/min/min. 
While pumping will usually be required to maintain adequate perfusion, in 
some instances passive perfusion may be sufficient. In particular, 
perfusion of the smaller arteries within the cerebral vasculature can 
sometimes be provided using a perfusion conduit having inlet ports or 
apertures on a proximal portion of the conduit and outlet ports or 
apertures on a distal portion of the conduit. By then positioning the 
inlet and outlet ports on the proximal and distal sides of the 
obstruction, respectively, the natural pressure differential in the 
vasculature will be sufficient to perfuse blood through the conduit lumen 
past the obstruction. Usually, the inlet ports on the perfusion conduit 
will be located at a location as close to the proximal side of the 
occlusion as possible in order to minimize the length of perfusion lumen 
through which the blood will have to flow. In some instances, however, it 
may be necessary to position the inlet ports sufficiently proximal to the 
occlusion so that they lie in a relatively patent arterial lumen to supply 
the necessary blood flow and pressure. The cross-sectional area of the 
perfusion lumen will be maintained as large as possible from the point of 
the inlet ports to the outlet ports. In this way, flow resistance is 
minimized and flow rate maximized to take full advantage of the natural 
pressure differential which exists. 
While perfusion is maintained through the perfusion conduit, treatment of 
the blood vessel blockage may be effected in a variety of ways. For 
example, thrombolytic, anticoagulant and/or anti-restenotic agents, such 
as tissue plasminogen activator (tPA), streptokinase, urokinase, heparin, 
or the like, may be administered to the patient locally (usually through 
the perfusion catheter) or systemically. In a preferred aspect of the 
present invention, such thrombolytic and/or anticoagulant agents may be 
administered locally to the arterial blockage, preferably through a lumen 
in the perfusion catheter itself. Such local administration can be 
directly into the thrombus, e.g., through side infusion ports which are 
positioned within the thrombus while the perfusion port(s) are positioned 
distal to the thrombus. Optionally, a portion of the blood which is being 
perfused could be added back to or otherwise combined with thrombolytic 
and/or anticoagulant agent(s) being administered through the catheter. The 
addition of blood to certain thrombolytic agents will act to catalyze the 
desired thrombolytic activity. The availability of the patient blood being 
perfused greatly facilitates such addition. It would also be possible to 
deliver the agent(s) through the same lumen and distal port(s) as the 
blood being pumped back through the perfusion lumen so that the agents are 
delivered distally of the catheter. The latter situation may be used 
advantageously with neuroprotective agents, vasodilators, antispasmotic 
drugs, angiogenesis promoters, as well as thrombolytics, anticoagulants, 
and anti-restenotic agents, and the like. The two approaches, of course, 
may be combined so that one or more agents, such as thrombolytic agents, 
are delivered directly into the thrombus while neuroprotective or other 
agents are delivered distally to the thrombus. Moreover, such delivery 
routes can also be employed simultaneously with systemic delivery of drugs 
or other agents to the patient. 
Alternatively or additionally, mechanical interventions may be performed 
while the vasculature is being perfused according to the present 
invention. For example, a perfusion conduit may have a very low profile 
and be used as a guide element to introduce an interventional catheter, 
such as an angioplasty catheter, an atherectomy catheter, a 
stent-placement catheter, or the like. 
The perfusion of the oxygenated medium may be performed for a relatively 
short time in order to relieve ischemia while other interventional steps 
are being taken, or may be performed for a much longer time either in 
anticipation of other interventional steps and/or while other long-term 
interventions are being performed. In particular, when thrombolytic and/or 
anticoagulant agents are being used to treat the primary blockage, the 
perfusion can be continued until the blockage is substantially relieved, 
typically for at least thirty minutes, often for four to eight hours, or 
longer. In other instances, perfusion can be maintained for much longer 
periods, e.g., more than one week, more than two weeks, more than a month, 
or even longer. 
In addition to delivering oxygen to the ischemic region distal to the 
primary occlusion, the blood or other oxygenated medium may carry other 
treatment agents, including thrombolytic agents, anticoagulant agents, 
tissue preservative agents, and the like. Moreover, in order to further 
preserve the cerebral tissue distal to the blockage, the oxygenated medium 
may be cooled to below body temperature, e.g., to a temperature in the 
range from 2.degree. C. to 36.degree. C., typically from 25.degree. C. to 
36.degree. C., in order to cool and preserve the tissue. Cooling may be 
effected externally as part of the extracorporeal pumping system and/or 
may be effected using a thermoelectric or Joule-Thomson expansion cooler 
on the catheter itself. 
Patients suffering from ischemia resulting from acute or chronic occlusion 
in the cerebral vasculature may be treated according to a preferred 
method. A perfusion conduit is introduced to the patient's vasculature, 
and a distal port on the conduit is guided through the occlusion in the 
cerebral vasculature. Blood, optionally oxygenated and/or superoxygenated, 
is obtained from the patient and perfused back to the patient through the 
distal port on the conduit past the occlusion at a rate sufficient to 
relieve the ischemia. The oxygenated blood may be arterial blood which may 
be returned to the patient without further oxygenation. Alternatively, 
arterial or venous blood can be oxygenated in suitable apparatus external 
to the patient and returned to the patient. External oxygenation allows 
the blood to be "superoxygenated," i.e., oxygenated at higher levels than 
would normally be available from arterial blood. Usually, the method 
further comprises delivering a therapeutic agent to the patient while the 
perfusing step is continued, usually being a thrombolytic agent which is 
delivered through the conduit directly to the vascular occlusion. The 
occlusion is usually in either a carotid artery, vertebral artery, 
proximal subclavian artery, brachiocephalic artery, or an intracerebral 
artery, and the conduit is usually introduced via the femoral artery in a 
conventional intravascular approach, typically being positioned over a 
guidewire which is first used to cross the occlusion. Alternatively, the 
conduit may be introduced through the axillary or brachial arteries, also 
in a conventional manner. 
Apparatus according to the present invention comprises perfusion/infusion 
catheters which include a catheter body having a proximal end and a distal 
end. The catheter body has at least two lumens, which may be formed as 
part of a single extrusion or which may be formed as separate tubes. When 
formed as separate tubes, the tubes may be fixed relative to each other or 
may be provided with appropriate sliding seals to permit them to slide 
relative to each other. Additional lumens and/or tubes may also be 
provided for purposes discussed in more detail below. Often, although not 
always, the catheters will be free from external dilatation balloons or 
other external structure which could complicate penetration of the distal 
end of the catheter through an obstruction. 
A first embodiment of the catheter is characterized by a large diameter 
proximal section and a small diameter distal section, where at least two 
isolated lumens extend from the proximal end of the catheter body through 
both sections to near the distal end of the catheter body. One of the 
lumens will extend entirely through the catheter body and usually have 
side ports over a distal length thereof. The other lumen will usually 
terminate some distance proximal of the distal tip of the catheter body 
and will also usually have side ports over a distal length thereof. The 
proximal section has an outer diameter in the range from 1 mm to 3 mm, 
usually from 1.5 mm to 2.5 mm, and typically from 1.5 mm to 2 mm, and the 
distal section has an outer diameter in the range from 0.5 mm to 2 mm, 
preferably from 0.5 mm to 1.5 mm. The first isolated lumen which extends 
entirely through the catheter body will usually be tapered, i.e., have a 
larger diameter over a proximal length thereof than over a distal length 
thereof. Usually, the first isolated lumen will have an inner diameter in 
the range from 0.75 mm to 1.25 mm in the proximal section, more usually 
being from 0.9 mm to 1.1 mm in the proximal section, and an inner diameter 
in the range from 0.25 mm to 1 mm in the distal section, usually being 
from 0.3 mm to 0.75 mm in the distal section. The second isolated lumen 
will usually be disposed annularly about the first isolated lumen and will 
have an inner diameter in the range from 0.9 mm to 2.9 mm in the proximal 
section, usually from 1.4 mm to 1.9 mm in the proximal section, and an 
inner diameter in the range from 0.4 mm to 1.9 mm in the distal section, 
usually in the range from 0.5 mm to 1.5 mm in the distal section. The 
second, outer annular lumen will typically terminate from 5 cm to 25 cm 
from the distal end of the catheter body. 
Apparatus according to the present invention further comprises systems 
including a perfusion/infusion catheter as set forth above in combination 
with a sheath for percutaneously introducing the perfusion/infusion 
catheter and a pump for receiving blood from the sheath and delivering 
blood back to the catheter. Optionally, an infusion device may be provided 
in the system for infusing a drug to a lumen of the perfusion/infusion 
catheter. 
The present invention still further comprises kits, including a perfusion 
catheter and instructions for use setting forth a method for penetrating 
the catheter through a blockage in a patient's vasculature and thereafter 
perfusing an oxygenated medium through the conduit to relieve ischemia. 
Kits will usually further comprise a container, such as a pouch, tray, 
box, tube, or the like, which contains the catheter as well as the 
instructions for use. Optionally, the instructions for use set forth on a 
separate instructional sheet within the package, but alternatively could 
be printed in whole or in part on the packaging itself. Optionally, other 
system components useful for performing the methods of the present 
invention could be provided within the kit, including guidewires, 
introductory sheaths, guiding catheters, and the like.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS 
The general principles of the present invention for treating partial and 
total occlusions within a patient's vasculature will be described in 
connection with FIGS. 1A-1C. A blood vessel BV which is usually an artery, 
more usually a cerebral artery, such as a carotid artery, vertebral 
artery, or an intracerebral artery, is obstructed by a total occlusion TO. 
The occlusion may result from thrombosis at a pre-existing atherosclerotic 
lesion or may result from the shedding of an embolus from an artery which 
flows distally to the particular vessel in which the occlusion occurs. 
Usually, the occlusion will occur abruptly and the sudden loss of 
perfusion through the blood vessel distal to the total occlusion TO will 
place the patient at great risk of neuron death. As discussed above in the 
Background section, it is usually necessary to reestablish perfusion 
within a matter of hours in order to avoid significant tissue damage or 
death, particularly in the case of strokes. While six hours is often 
considered a maximum delay, earlier treatment is much more desirable. 
The present invention provides a method for very quickly reestablishing 
perfusion through the total occlusion TO. Such perfusion is established 
using a perfusion conduit 10 (FIG. 1C) through which oxygenated blood or 
an oxygenated synthetic medium, such as a perfluorocarbon oxygen carrier, 
is actively pumped back through a lumen of the catheter from a source 12. 
Usually, the conduit will include side perfusion ports 14 near its distal 
end 16 in order to enhance perfusion and reduce hemolysis (when blood is 
the oxygenated medium). Optionally, proximal portions of the conduit 10 
(not shown) may have enlarged lumen diameters in order to reduce flow 
resistance and shear forces to further reduce or prevent hemolysis. It 
will be appreciated that while the distal portion of the conduit 10 will 
usually have a relatively low profile to access small diameter blood 
vessels, the proximal portions can be made significantly larger to improve 
the hemodynamic flow and handling characteristics and reduce hemolysis. 
Optionally, the conduit 10 will be introduced over a conventional guidewire 
GW which is initially used to cross the total occlusion TO, as shown in 
FIG. 1B. In other instances, however, the perfusion conduit 10 may be 
adapted so that it is able to cross the total occlusion TO without the use 
of a conventional guidewire. In some cases, the perfusion conduit may be 
in the form of a guidewire, e.g., a tapered guidewire, which is suitable 
for both guiding through the vasculature to the site of the total or 
partial occlusion as well as crossing the occlusion. 
The perfusion conduit 10 may be introduced from any normal intravascular 
introduction site, e.g., through the femoral artery using the Seldinger 
technique. Alternatively, the infusion conduit can be introduced through 
the axillary and other arteries. 
A system 20 suitable for treating occlusions within the cerebral 
vasculature is illustrated in FIGS. 2-6. The system 20 includes a 
perfusion conduit in the form of intravascular catheter 22. The catheter 
22 comprises a catheter body 24 having a distal end 26 and a proximal end 
28. The catheter body 24 comprises a pair of coaxial tubular elements, 
including an outer tube 30 and an inner tube 32. Proximal hub 34 comprises 
a first port 36 which is fluidly coupled to an interior lumen of the inner 
tube 32 and a second port 38 which is fluidly coupled to an annular lumen 
between the exterior surface of inner tube 32 and the interior of tube 30. 
Proximal port 40 (typically a hemostasis valve) also communicates with the 
lumen of the inner tube 32 and is suitable for intravascular positioning 
of the catheter 22 over a guidewire. 
The system usually further includes a guiding catheter 50 having dimensions 
and characteristics suitable for introducing the catheter 22 to the 
desired intravascular target site. Although illustrated as having a 
straight configuration, the guiding catheter 50 will often have a 
preformed, curved tip selected specifically to reach the intravascular 
target site, and the guiding catheter could further be reinforced (e.g., 
braided), have a variable stiffness over its length, have a variable 
diameter, or the like. The system 20 will usually still further comprise a 
sheath 60 which is used to percutaneously access the vasculature at the 
introductory site, e.g., in the femoral artery. The sheath 60 has a 
proximal hub 61 including at least one side arm 62. The hub 61 receives 
the catheter 22 therethrough and will include a mechanism for maintaining 
hemostasis about the catheter. The side arm 62 permits withdrawal of blood 
for oxygenation and return to the patient according to the present 
invention. Other side arm(s) may be provided for removal of blood 
(optionally combined with drugs being delivered back to the patient), for 
infusing agents through the sheath 60, or for other purposes. Entry of 
blood into the lumen of the sheath is optionally facilitated by side ports 
64 formed over at least a distal portion of the sheath. 
The catheter body 24 is tapered in the distal direction, i.e., the diameter 
is larger near the proximal end 28 than at the distal end 26. As 
illustrated in FIGS. 2-6, the outer tube 30 has a large diameter proximal 
section (observed in FIG. 3) and a smaller diameter distal section 
(observed in FIGS. 4 and 5). Similarly, the inner tube 32 has a large 
diameter proximal section (shown in FIG. 3) and a smaller diameter distal 
section (shown in FIGS. 4-6). The particular outer diameters and inner 
lumen diameters of both the outer tube 30 and inner tube 32 are within the 
ranges set forth above. Since the distal terminii of the outer tube 30 and 
inner tube 32 are staggered, the catheter body 24 is tapered in three 
stages, with a first diameter reduction occurring at location 33 (FIG. 2) 
where the diameter of the outer tubular member 30 is reduced from the 
diameter shown in FIG. 3 to the diameter shown in FIG. 4. The second 
diameter reduction occurs at location 35 where the outer tubular member 30 
terminates, leaving the outer surface of the inner tubular member 32 to 
define the catheter body. 
Such tapered configurations are preferred since they maximize the 
cross-sectional area of the flow lumens over the length of the catheter to 
reduce flow resistance for both the blood (or other oxygenated medium) and 
the drug to be delivered. As can be seen in FIG. 3, lumen 70 of the inner 
tubular member 32 which carries the blood is maximized until the diameter 
is reduced near the distal end of the catheter, as shown in FIG. 4. 
Similarly, the annular lumen 72 which carries the drug is maximized over 
the proximal portion before it is reduced after the transition at location 
33. Maintaining the larger diameters and lumen areas is desirable in order 
to decrease flow resistance and shear forces to reduce or eliminate 
hemolysis as the blood is introduced through the entire catheter length. 
Similarly, a reduction in flow resistance to the drug being introduced 
facilitates drug delivery during the procedure. 
Side wall penetrations 80 are provided in a distal portion 26 of the outer 
tubular member 30, as best seen in FIGS. 2 and 5. The penetrations 80 will 
be useful for delivering a therapeutic agent through port 38 in order to 
treat the primary occlusion, as described in more detail hereinafter. 
Similarly, ports 90 may be formed over at least a distal portion of the 
inner tubular member 32 which extends beyond the distal end of the outer 
tubular member 30. The penetrations 90 will be available to release blood 
or other oxygenated medium that is being perfused back to the patient 
through port 36 and the continuous lumen of the tube 32. Note that while 
the lumen 70 of tube 32 will be available for introduction of the catheter 
22 over a guidewire, the guidewire may be at least partially withdrawn 
from the lumen 70 in order to further decrease blood flow resistance as it 
is perfused back to the patient. 
Optionally, the catheter 22 may comprise at least one pressure sensing 
element 96 disposed at a location near where the blood or other oxygenated 
medium is returned to the blood vessel. Preferably, the pressure sensing 
element 96 may be a piezoelectric or other solid state pressure sensing 
device and will be connected through the hub 34 by a pair of wires 97 
which may be connected to conventional electronic devices for measuring 
pressure. Thus, pressure may be measured and used for controlling rate 
and/or pressure of blood or other oxygenated medium pumped back to the 
patient using conventional analog or digital control circuitry. A pressure 
control point will be selected, usually within the ranges set forth above, 
and the rate or pressure of oxygenated medium being pumped back through 
the catheter 22 will be controlled to maintain the control point. 
Conventional control algorithms, such as proportional, derivative, 
integral, and combinations thereof, may be employed for maintaining the 
desired control point. 
In some instances, it will be desirable to provide at least a second 
pressure sensing element 98 which will be located proximal to the 
obstruction when the catheter is in use. For example, the pressure sensing 
element 98 may be near the location 35 where the outer tubular member 30 
terminates. The sensor 98 will permit monitoring of the pressure in the 
vasculature proximal of the occlusion, which pressure will usually 
approximate that of the vasculature in the region of the occlusion prior 
to an acute occlusion event. This pressure, in turn, may be utilized as a 
target pressure for the blood or other oxygenated medium which is being 
perfused distal to the occlusion. That is, it may be desirable to treat 
the measured "background" pressure as a maximum desirable pressure for 
perfusion in order to prevent injury to the vasculature distal to the 
occlusion. 
Referring now to FIG. 7, use of the system 20 for treating the cerebral 
vasculature of a patient P will be described. Access to the target 
cerebral artery is established using the sheath 60 in a conventional 
manner. The guiding catheter 50 is then introduced through the sheath 60 
and establishes a protected access lumen to a location within the cerebral 
vasculature. The catheter 22 is then introduced through the guiding 
catheter to the target site within the cerebral vasculature, typically 
over a guidewire (not illustrated). Conveniently, the catheters will be 
partly radiopaque and/or radiopaque markers 92 (FIG. 2) will be provided 
at the distal tip of the catheter as well as on either side of the drug 
ports 80 so that the catheter 22 may be properly positioned under 
fluoroscopic guidance relative to the obstruction being treated. After the 
tip 26 of the catheter 22 is penetrated through the occlusion TO (FIG. 8) 
the penetrations 80 are preferably located within the occlusive material 
in order to deliver the thrombolytic or other agent to the material. The 
distal portion of the catheter, including ports 90, in contrast, are 
located beyond the occlusive material in order to provide the desired 
blood perfusion. Blood flow is immediately established using an external 
pump 100 which receives blood from the port 62 of access sheath 60 and 
returns the oxygenated blood to the catheter 22 through port 36. A 
therapeutic agent, typically a thrombolytic agent, may be simultaneously 
introduced through port 38 from a source 102 in order to treat the 
occlusion TO. Optionally, the blood may be cooled before, during, or after 
it has passed through the pump unit 100. Still further optionally, the 
blood may be oxygenated or superoxygenated using an oxygen-saturated 
bubble chamber or conventional cardiopulmonary bypass oxygenators. In some 
instances, it may be desirable to combine the thrombolytic agent with a 
portion of the recirculating blood before infusing the thrombolytic 
agent/blood back through the port 38. 
Kits according to the present invention are illustrated in FIG. 9. The kit 
will include a perfusion conduit, such as perfusion conduit 10, as well as 
instructions for use 120. The catheter and instructions for use will 
usually be combined within a suitable container C, such as a pouch, tray, 
box, tube, or the like. The catheter and possibly other components of the 
system (such as guide catheters, sheaths, thrombolytic or other 
therapeutic agents, disposable cartridges for pump/oxygenation systems, or 
the like) will optionally be included and/or sterilized within the 
packaging. The instructions for use may be on a separate sheet of paper or 
may be printed in whole or in part on the packaging materials. 
Referring now to FIG. 10, a perfusion conduit 200 includes an inner tube 
202 and outer tube 204. The inner tube has perfusion ports 206 formed in 
its side wall over a portion of the distal end, and the outer tube 204 has 
perfusion ports 208 formed over a portion of its distal end. The perfusion 
conduit 200 differs from catheter 22 primarily in that the inner tubular 
member 202 is able to slide axially relative to the outer tubular member 
204. A sliding seal 210, typically an O-ring or similar passive seal, is 
provided to maintain pressure within the lumen of outer tubular member 204 
so that thrombolytic and other drugs can be delivered without excessive 
loss through the distal tip. Some loss of the agent, however, will usually 
be acceptable so that the seal need not be completely tight. If a more 
positive seal is desired, an inflatable balloon 211 (shown in broken line) 
may be provided in addition to or in place of the sliding seal 210. Use of 
the balloon 211 is advantageous in that it permits higher infusion 
pressures without leakage from the distal end of the outer tube 204, but 
disadvantageous in that it limits the range of axial placement of the 
outer tube 204 relative to the inner tube 202. Use of the inner tube 202 
for perfusing blood or other oxygenated medium therethrough will generally 
be as described with the prior embodiments. Radiopaque markers 212 and 214 
on the inner tube 202 will be positioned distally of the occlusion to 
assure that the perfusion ports 206 will release the delivered blood with 
minimal resistance. Radiopaque markers 216 and 218 on outer tube 208, in 
contrast, will be positioned so that the infusion ports 208 lie generally 
within the occluded region. Optionally, the balloon 212 will be inflated 
to both lock the inner and outer tubes relative to each other and to 
provide a positive seal at the distal end of the outer tube, and the 
thrombolytic or other therapeutic agent will then be delivered through the 
lumen of the outer tube into the occlusive material, such as thrombus. 
Referring now to FIG. 11, a perfusion conduit 300 also includes an inner 
tube 302 and an outer tube 304. The inner and outer tubes are slidable 
relative to each other, and a sliding seal 310 is provided at the distal 
end of the outer tube 304. The perfusion conduit 300, in contrast to prior 
embodiments, is not intended to deliver a therapeutic agent. Instead, it 
is intended only to perfuse blood or other oxygenated medium therethrough. 
The lumen 312 within the outer tube 304 is intended for passing the blood 
or other oxygenated medium to near the distal end of the conduit 300. The 
inner tube 302 then receives the blood or other oxygenated medium through 
ports 314 which permit the medium to flow from lumen 312 into the interior 
lumen of the tube 302. An enlarged portion 316 of the tube 302 is provided 
in order to prevent axial advancement of the tube so that the ports 314 
cannot extend outside of the outer tube 304. Alternatively or 
additionally, an inflatable balloon 316 may be provided in order to both 
prevent excess axial advancement of the inner tube 302 and provide a more 
positive seal. Usually, since the blood will be perfused at lower 
pressures than might be used for drug delivery, use of the balloon 316 for 
isolation will often not be necessary. The perfusion conduit 300 can thus 
provided reduced flow resistance for the blood or other oxygenated medium 
being returned to the patient through the conduit. Additionally, the 
ability to slide the outer tube 304 relative to the inner tube 302 helps 
the tubes be properly positioned relative to each other depending on the 
circumstances of the patient being treated. 
Referring now to FIG. 12, a perfusion conduit 400 intended for passive 
perfusion, i.e., without active pumping, is illustrated. The catheter 400 
usually comprises a single extrusion having a proximal section 402 with an 
enlarged diameter 412 and a distal section 404 with a reduced diameter. 
The proximal and distal diameters will generally be in the ranges set 
forth above. Blood inlet ports 408 are provided on the catheter near its 
proximal end while blood outflow ports 410 are provided near the distal 
end. The relative positions of the inflow ports 408 and outflow ports 410 
allow the perfusion conduit 400 to be introduced to a patient so that the 
inflow ports are proximal to the occlusion while the outflow ports 410 are 
distal to the occlusion. The inflow ports 408 are usually relatively near 
to the distal end of the proximal section 402 having the enlarged diameter 
in order to decrease the overall flow resistance between the inflow ports 
408 and outflow ports 410. Generally, however, the inflow ports 408 will 
be positioned so that they will lie proximally of the occlusion so that 
the occluding material does not block blood flow into the inflow ports. In 
some instances, they will be spaced proximally of the transition 412 from 
large diameter to small diameter by a distance in the range from 1 cm to 
15 cm, usually from 2 cm to 10 cm, to assure proper placement in the 
vasculature. The inflow ports 408 are thus able to receive blood and pass 
the blood distally through the large diameter section with minimum 
pressure drop. A pressure drop through the narrow diameter section 404 
will be greater, in many instances the total pressure drop of the conduit 
400 will be sufficiently low so that adequate blood perfusion can be 
maintained to relieve patient ischemia. Optionally, the conduit 400 could 
have a slidable structure, as shown in conduit 300 of FIG. 11, but such 
structure will increase the flow resistance and will not be preferred in 
all instances. 
While the above is a complete description of the preferred embodiments of 
the invention, various alternatives, modifications, and equivalents may be 
used. Therefore, the above description should not be taken as limiting the 
scope of the invention which is defined by the appended claims.