Patent Publication Number: US-2005124973-A1

Title: Apparatus and methods for treating stroke and controlling cerebral flow characteristics

Description:
RELATED APPLICATIONS  
      The present application is a divisional of copending U.S. patent application Ser. No. 09/972,225, filed Oct. 4, 2001. 
    
    
     FIELD OF THE INVENTION  
      The present invention relates to improved apparatus and methods for treatment of stroke. More specifically, the apparatus and methods of the present invention are directed to treating stroke by controlling cerebral blood flow and removing thrombi and/or emboli.  
     BACKGROUND OF THE INVENTION  
      Cerebral occlusions that lead to stroke require swift and effective therapy to reduce morbidity and mortality rates associated with the disease. Many current technologies for treating stroke are inadequate because emboli generated during the procedure may travel downstream from the original occlusion and cause ischemia. There is currently a need for a stroke treatment system that provides a swift and efficient treatment for occlusions while simultaneously controlling cerebral flow characteristics.  
      In the initial stages of stroke, a CT scan or MRI may be used to diagnose the cerebral occlusion, which commonly occurs in the middle cerebral arteries. Many current technologies position a catheter proximal to the occlusion, then deliver clot dissolving drugs to treat the lesion. A drawback associated with such technology is that delivering drugs may require a period of up to six hours to adequately treat the occlusion. Another drawback associated with lytic agents (i.e., clot dissolving agents) is that they often facilitate bleeding.  
      When removing thrombus using mechanical embolectomy devices, it is beneficial to engage the thrombus and remove it as cleanly as possible, to reduce the amount of emboli that are liberated. However, in the event that emboli are generated during mechanical disruption of the thrombus, it is imperative that they be subsequently removed from the vasculature.  
      Many current drug delivery and mechanical treatment methods are performed under antegrade flow conditions. Such treatment methods do not attempt to manipulate flow characteristics in the cerebral vasculature, e.g, the Circle of Willis and communicating vessels, such that emboli may be removed. Accordingly, there remains a need to provide effective thrombus and emboli removal from the cerebral vasculature while simultaneously controlling flow within that vasculature.  
      U.S. Pat. No. 6,161,547 to Barbut (Barbut &#39;547) describes a technique for enhancing flow in the cerebral vasculature in treating patients with acute stroke or other cerebrovascular disease. The technique involves: (1) positioning a first tubular member in a vascular location suitable for receiving antegrade blood flow; (2) positioning a second tubular member in a contralateral artery of the occlusion (e.g., for an occlusion located in the left common carotid artery the second tubular member is placed in the right common carotid artery); and coupling the first tubular member to the second tubular member using a pump and filter.  
      The first tubular member receives antegrade blood flow and channels the blood to the pump and filter, where the blood then is reperfused via the second tubular member into the contralateral artery, thus increasing blood flow to the opposing hemisphere of the brain. The first and second tubular members may include balloons disposed adjacent to their distal ends.  
      The techniques described in the foregoing patent have several drawbacks. For example, if the first balloon of the first tubular member is deployed in the left common carotid artery, as shown in  FIG. 7C , aspiration of blood from the vessel between the balloon and the occlusion may cause the vessel to collapse. On the other hand, if the balloon is not deployed, failure to stabilize the distal tip may result in damage to the vessel walls. In addition, failure to occlude the vessel may permit antegrade blood flow to diverted into that apparatus, rather than blood distal to the first tubular member.  
      The Barbut &#39;547 patent further discloses that inflating the balloon of the second tubular member may assist in controlling the flow to the contralateral artery or provide more efficient administration of pharmacotherapy to the cerebral tissues. However, when that balloon is deployed, the contralateral artery may be starved of sufficient flow, since the only other flow in that artery is that aspirated through the first tubular member. On the other hand, if the balloon of the second tubular member is not inflated, no flow control is possible.  
      A method for removing cerebral occlusions is described in U.S. Pat. No. 6,165,199 to Barbut (Barbut &#39;199). This patent describes a catheter having an aspiration port at its distal end that communicates with a vacuum at its proximal end. A perfusion port disposed in a lateral surface of the catheter may be used to enhance antegrade flow in collateral arteries. In use, the aspiration port is positioned proximal to an occlusion to provide a direct suction effect on the occlusion. The perfused flow in collateral arteries is intended to augment retrograde flow distal to the occlusion, such that the occlusion is dislodged via the pressure and directed toward the aspiration port. A chopping mechanism, e.g., an abrasive grinding surface or a rotatable blade, coupled to the aspiration port recognizes when the aspiration port is clogged. The chopping mechanism then engages to break up the occlusion and permit it to enter the aspiration port in smaller pieces.  
      The device described in the Barbut &#39;199 patent has several disadvantages. First, the use of a vacuum to aspirate the occlusion requires an external pressure monitoring device. The application of too much vacuum pressure through the aspiration port may cause trauma, i.e., collapse, to the vessel wall. Also, because the system is intended to dislodge the occlusion using a pressure differential, a chopping mechanism is required to prevent the entire mass from clogging the aspiration port. The use of a chopping mechanism, however, may generate such a large quantity of emboli that it may be difficult to retrieve all of the emboli. In addition, emboli generated by the action of the chopping mechanism may accumulate alongside the catheter, between the aspiration port and the distal balloon. Once this occurs, it is unclear how the emboli will be removed.  
      Yet another drawback of the device described in the Barbut &#39;199 patent is that high-pressure perfusion in collateral arteries may not augment retrograde flow distal to the occlusion as hypothesized. The patent indicates that high-pressure perfusion in collateral arteries via side ports in the catheter may be sufficient to cause an increase in pressure distal to the occlusion. Antegrade blood flow from the heart in unaffected arteries, e.g., other vertebral and/or carotid arteries, may make it difficult for the pressure differential induced in the contralateral arteries to be communicated back to the occluded artery in a retrograde fashion.  
      Other methods for treating ischemic brain stroke have involved cerebral retroperfusion techniques. U.S. Pat. No. 5,794,629 to Frazee describes a method that comprises at least partially occluding the first and second transverse venous sinuses and introducing a flow of the patient&#39;s arterial blood to a location distal to the partial venous occlusions. As described in that patent, the infusion of arterial blood into the venous sinuses provides a retrograde venous flow that traverses the capillary bed to oxygenate the ischemic tissues and at least partially resolve ischemic brain symptoms.  
      One drawback associated with the technique described in the Frazee patent is that the pressure in the transverse venous sinuses must be continuously monitored to ensure that cerebral edema is avoided. Because the veins are much less resilient than arteries, the application of sustained pressure on the venous side may cause brain swelling, while too little pressure may result in insufficient blood delivered to the arterial side.  
      In addition to the foregoing methods to augment cerebral perfusion, several methods are known for mechanically removing clots to treat cerebral occlusions. U.S. Pat. No. 5,895,398 to Wensel et al. describes a shape-memory coil affixed to an insertion mandrel. The coil is contracted to a reduced profile state within the lumen of a delivery catheter, and the catheter is used to cross a clot. Once the coil is disposed distal to the clot, the coil id deployed. The coil then is retracted proximally to engage and remove the clot.  
      A primary drawback associated with the Wensel device is that the deployed coil contacts the intima of the vessel, and may damage to the vessel wall when the coil is retracted to snare the occlusion. Additionally, the configuration of the coil is such that the device may not be easily retrieved once it has been deployed. For example, once the catheter has been withdrawn and the coil deployed distal to the occlusion, it will be difficult or impossible to exchange the coil for another of different dimensions.  
      U.S. Pat. No. 5,972,019 to Engelson et al. describes a deployable cage assembly that may be deployed distal to a clot. Like the Wensel device, the Engelson device is depicted as contacting the intima of the vessel, and presents the same risks as the Wensel device. In addition, because the distal end of the device comprises a relatively large profile, the risk of dislodging emboli while crossing the clot is enhanced, and maneuverability of the distal end of the device through tortuous vasculature may be reduced.  
      In view of these drawbacks of previously known clot removal apparatus and methods, it would be desirable to provide apparatus and methods for controlling hemodynamic properties at selected locations in the cerebral vasculature, e.g., the Circle of Willis and communicating vessels.  
      It also would be desirable to provide apparatus and methods for removal and recovery of thrombi and/or emboli above the carotid bifurcation.  
      It still further would be desirable to provide apparatus and methods that quickly and efficiently treat cerebral occlusions.  
      It still further would be desirable to provide apparatus and methods for selectively providing retrograde and/or antegrade flow to desired regions in the cerebral vasculature to effectively remove emboli.  
     SUMMARY OF THE INVENTION  
      In view of the foregoing, it is an object of the present invention to provide apparatus and methods for controlling hemodynamic properties at selected locations in the cerebral vasculature.  
      It is also an object of the present invention to provide apparatus and methods for removal and recovery of thrombi and/or emboli above the carotid bifurcation.  
      It is a further object of the present invention to provide apparatus and methods that quickly and efficiently treat cerebral occlusions.  
      It still a further object of the present invention to provide apparatus and methods for selectively providing retrograde and/or antegrade flow to desired regions in the cerebral vasculature to effectively remove emboli.  
      These and other objects of the present invention are accomplished by providing a stroke treatment system comprising an emboli removal catheter and one or more flow control devices suitable for manipulating blood flow in the cerebral vasculature. The stroke treatment system may facilitate the introduction and subsequent removal of clot lysing agents, or further comprise a thrombectomy element.  
      In a preferred embodiment, the emboli removal catheter is transluminally inserted and disposed in the common carotid artery CCA, and comprises a flexible catheter having an occlusive member disposed on its distal end. The occlusive member is configured to be deployed to anchor the catheter and occlude antegrade flow in the CCA. A separate occlusive element is configured to pass through a lumen of the emboli removal catheter, and is deployed in the external carotid artery ECA to occlude flow through that vessel.  
      One or more flow control devices, each having a rapidly deployable occlusive member, then are positioned at selected locations, e.g., in the subclavian arteries, and may be deployed to isolate or redistribute flow through the cerebral vasculature. Preferably, the flow control devices occlude blood flow in the vertebral and carotid arteries in the hemisphere in which the occlusion is not located. This temporarily influences flow in the opposing hemisphere. Preferably, the flow control devices are provided in sufficient number that, when deployed, the flow control devices substantially influence the flow dynamic of mid-cerebral artery.  
      Once the foregoing components have been deployed, a lysing agent may be introduced into the vessel through a lumen of the emboli removal catheter. After an appropriate period, the occlusive members on one or more of the flow control devices may be collapsed to cause retrograde flow through the cerebral vasculature sufficient to flush the lysing agent and any emboli or debris from the vasculature into the emboli removal catheter. The stroke treatment system and flow control devices may then be withdrawn from the patient&#39;s vasculature.  
      Alternatively, a thrombectomy element may be advanced transluminally via the ICA to a position just proximal of a cerebral occlusion, e.g., in the middle cerebral artery, after placement (but prior to deployment) of the flow control devices. The flow control devices then are deployed to selectively and temporarily redistribute or suspend flow in the cerebral vasculature. The thrombectomy element preferably is advanced to the site of the cerebral occlusion through a lumen of the emboli removal catheter.  
      With flow controlled throughout the Circle of Willis and therefore the communicating mid-cerebral artery, the thrombectomy element then is engaged with the lesion. Actuation of the thrombectomy element preferably causes mechanical disruption of the emboli or thrombus, after which the element is retracted into the emboli removal catheter. By selectively de-actuating one or more of the flow control devices, retrograde or redistributed flow may be generated in the vasculature that cases emboli liberated during actuation of the thrombectomy element to be directed into the emboli removal catheter. The flow control devices then are withdrawn to reestablish antegrade blood flow.  
      In a further alternative embodiment, a second emboli removal catheter may be disposed in a vertebral artery in lieu of one of the flow control devices. In this embodiment, the lumen of the second emboli removal catheter may be perfused with blood or saline under pressure to induce retrograde flow elsewhere in the cerebral vasculature, such as in the carotid or vertebral arteries. Additionally, chilled blood and/or drug agents may be delivered via the second catheter to induce mild hypothermia and/or altered pressure gradients at selected cerebral locations.  
      The second emboli removal catheter may be used to enhance flow manipulation in the Circle of Willis and communicating vessels to facilitate removal of emboli via either retrograde or antegrade flow either independently or, or simultaneously with, use of the first emboli removal catheter. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
      Further features of the invention, its nature and various advantages will be more apparent from the accompanying drawings and the following detailed description of the preferred embodiments, in which:  
       FIG. 1  provides a schematic overview of the portion of the vasculature in which the apparatus and methods of the present invention are intended for use;  
       FIG. 2  provides an overview of the apparatus of the present invention deployed in a patient&#39;s vasculature;  
       FIGS. 3A-3D  are, respectively, a schematic view, and detailed side and sectional views of the distal end of an emboli removal catheter of the present invention;  
       FIGS. 4A-4E  provide detailed views of the proximal and alternative distal ends of the flow control devices of the present invention contracted and expanded states;  
       FIGS. 5A-5B  are views of alternative embodiments of low profile occlusive elements for occluding flow in the external carotid arteries;  
       FIGS. 6A-6F  depict thrombectomy wires having shape memory properties in contracted and deployed states;  
       FIGS. 7A-7E  illustrate alternative configurations for the thrombectomy wire of  FIG. 6 ;  
       FIGS. 8A-8D  illustrate thrombectomy wires configured to engage the fibrin strands of a thrombus;  
       FIGS. 9A-9C  describe an alternative thrombectomy device configured to engage the fibrin strands of a thrombus;  
       FIGS. 10A-10E  illustrate method steps for removing an occlusion using the apparatus of  FIG. 9 ;  
       FIG. 11  describes a telescoping catheter configured to be advanced through the main catheter;  
       FIGS. 12A-12D  describe a telescoping catheter having an expandable distal section configured to be advanced through the main catheter;  
       FIGS. 13A-13H  illustrate method steps for controlling cerebral blood flow and removing thrombi and/or emboli in accordance with the present invention;  
       FIGS. 14A-14B  describe a catheter having an intake port configured to provide for retrograde and/or antegrade flow in either of the carotid or vertebral arteries;  
       FIG. 15  illustrates a proximal assembly suitable for controlling retrograde and antegrade flow in the carotid and vertebral catheters of  FIG. 14 ; and  
       FIGS. 16A-16B  provide examples of manipulating cerebral flow using a combination of carotid and vertebral catheters, each having antegrade and retrograde flow potential. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION  
      Referring to  FIG. 1 , a schematic of the pertinent vasculature relating to the present invention is provided. Many cerebral obstructions that lead to stroke reside in the middle cerebral arteries MCA. To treat obstructions in the MCA, one approach involves percutaneously and transluminally advancing a therapeutic device to the site of the obstruction via the internal carotid artery ICA.  
      It is well known in the art to percutaneously and transluminally advance a catheter in retrograde fashion toward coronary vasculature, e.g., via the femoral artery, external iliac artery, descending aorta DA and aortic arch AA. To access cerebral vasculature, including obstructions residing in the MCA, one approach is to further advance a catheter and/or therapeutic devices in antegrade fashion from the aortic arch AA, into the common carotid artery CCA, up through the ICA and into the middle cerebral artery MCA, as shown in  FIG. 1 .  
      Treating occlusions in the MCA may generate emboli upon removal of the occlusion. Under normal blood flow conditions, such emboli may travel downstream from the original occlusion and cause ischemia. Accordingly, it is advantageous to manipulate blood flow characteristics in the cerebral vasculature to ensure that emboli generated in the MCA are effectively removed.  
      The present invention manipulates cerebral blood flow by inhibiting flow from the heart into any of the vertebral arteries VA and common carotid arteries CCA. This may be achieved by disposing flow control devices in the subclavian arteries SA and/or brachiocephalic trunk BT, to temporarily inhibit flow from the aortic arch AA into any of the vertebral arteries VA and common carotid arteries CCA. This interruption of antegrade flow may advantageously alter flow in the Circle of Willis, as described hereinbelow.  
       FIG. 2  provides an overview of the components of the system of the present invention, each of which are described in greater detail hereinbelow.  
      Flow control devices  8  having occlusive elements  6  are configured to be introduced into the patient&#39;s vasculature, e.g., via the radial or brachial arteries. When so positioned, occlusive elements  6  preferably are positioned in the patient&#39;s left subclavian artery SA and brachiocephalic trunk BT, as shown. Occlusive elements  6  may have any of a number of designs, with low profile mechanically self-expanding designs being preferred.  
      Emboli removal catheter  2  includes distal occlusive element  4 , and is configured to be percutaneously advanced in retrograde fashion through the descending aorta. Occlusive element  4  preferably comprises a pear-shaped or funnel-shaped balloon as described in copending and commonly assigned U.S. patent application Ser. No. 09/418,727, which is incorporated herein by reference. Occlusive element  4  preferably is positioned proximal to the carotid bifurcation, and then deployed to induce retrograde flow in the ICA by use of a venous return catheter (not shown) that communicates with the proximal end of catheter  2 . Balloon  10 , also described in the foregoing application, is deployed in the ECA to ensure that retrograde flow from the ICA is not carried in an antegrade fashion into the ECA.  
      Flow control devices  8  and emboli removal catheter  2  are used to suspend antegrade flow in the cerebral arteries and to selectively suspend or redistribute flow in the cerebral vasculature. Once so-deployed, a lysing agent may be introduced to dissolve the clot, followed by selectively contracting one or more of the flow control devices to induce retrograde flow through emboli removal catheter  2 .  
      Alternatively, after placement of flow control devices  8 , but before they are deployed, thrombectomy wire  12  may be introduced into the vessel containing the lesion. Flow control devices  8  then may be deployed, as shown in  FIG. 2 , to prevent flow from the aortic arch AA into the right common carotid artery RCCA and the right and left vertebral arteries VA. Such selective manipulation of flow into the carotid and/or vertebral arteries alters flow characteristics in the cerebral vasculature, and permits retrograde flow through to be induced to flush emboli and debris into the lumen of catheter  2  for removal.  
      In the embodiment of  FIG. 2 , thrombectomy wire  12  comprises knot  14  that is deployed distal to the thrombus T. Thrombectomy wire  12  and thrombus T then are retracted proximally into the lumen of emboli removal catheter  2 , and any embolic fragments generated during this procedure are directed into catheter  2  by inducing localized retrograde flow. Once the thrombus is removed, flow control devices  8  are contracted to reestablish flow to the cerebral vasculature.  
      Referring now to  FIG. 3A , stroke treatment apparatus  40  constructed in accordance with the principles of the present invention is described. Apparatus  40  comprises emboli removal catheter  41 , wire  45 , venous return line  52 , tubing  49  and optional blood filter  50 .  
      Catheter  41  includes distal occlusive element  42 , hemostatic ports  43   a  and  43   b , e.g., Touhy-Borst connectors, inflation port  44 , and blood outlet port  48 . Wire  45  includes balloon  46  that is inflated via inflation port  47 . Tubing  49  couples blood outlet port  48  to filter  50  and blood inlet port  51  of venous return line  52 .  
      Wire  45  preferably comprises a small diameter flexible shaft having an inflation lumen that couples inflatable balloon  46  to inflation port  47 . Wire  45  and balloon  46  are configured to pass through hemostatic ports  43   a  and  43   b  and the aspiration lumen of catheter  41  (see  FIGS. 3C and 3D ), so that balloon  46  may be disposed in a communicating artery, e.g., the external carotid artery. Ports  43   a  and  43   b  and the aspiration lumen of catheter  41  are sized to permit additional interventional devices, such as thrombectomy wires, to be advanced through the aspiration lumen when wire  45  is deployed.  
      Venous return line  52  includes hemostatic port  53 , blood inlet port  51  and a lumen that communicates with ports  53  and  51  and tip  54 . Venous return line  52  may be constructed in a manner per se known for venous introducer catheters. Tubing  49  may comprise a suitable length of a biocompatible material, such as silicone. Alternatively, tubing  49  may be omitted and blood outlet port  48  of catheter  41  and blood inlet port  51  of venous return line  52  may be lengthened to engage either end of filter  50  or each other.  
      With respect to  FIGS. 3B and 3C , distal occlusive element  42  comprises expandable funnel-shaped balloon  55 . In accordance with manufacturing techniques which are known in the art, balloon  55  comprises a compliant material, such as polyurethane, latex or polyisoprene which has variable thickness along its length to provide a funnel shape when inflated. Balloon  55  is affixed to distal end  56  of catheter  41  in an inverted fashion, for example, by gluing or a melt-bond, so that opening  57  in balloon  55  leads into aspiration lumen  58  of catheter  41 . Balloon  55  preferably is wrapped and heat treated during manufacture so that distal portion  59  of the balloon extends beyond the distal end of catheter  41  and provides an atraumatic tip or bumper for the catheter.  
      As shown in  FIG. 3D , catheter  41  preferably comprises inner layer  60  of low-friction material, such as polytetrafluoroethylene (“PTFE”), covered with a layer of flat stainless steel wire braid  61  and polymer cover  62  (e.g., polyurethane, polyethylene, or PEBAX). Inflation lumen  63  is disposed within polymer cover  62  and couples inflation port  44  to balloon  55 .  
      Referring to  FIG. 4 , features of the flow control devices of the present invention are described. The flow control devices may comprise either an inflatable balloon or a mechanically deployable mechanism. In  FIG. 4A , a preferred embodiment of the proximal end for a mechanically deployable mechanism comprises controller  70 , delivery port  78 , e.g., for delivering cardioplegic agents, deployment knob  72  that is configured to slide within slot  74 , and guidewire lumen  76 , which may comprise a self-sealing valve. Body  73  houses a plurality of lumens, e.g., a mechanical deployment lumen, a therapeutic drug delivery lumen, and a guidewire lumen. In an alternative embodiment, for use in conjunction with an inflatable balloon, port  78  may serve as an inflation/aspiration port while deployment knob  72  and slot  74  are omitted.  
       FIGS. 4B-4C  illustrate the distal end of the flow control device having inflatable balloon  82  in contracted and deployed states, respectively. In use, body  73  is advanced over a guidewire via guidewire lumen  86 . Radiopaque tip marker  84  may be used to aid in fluoroscopically guiding the device. Balloon  82  then is inflated by a lumen within body  73  that communicates with port  78 . Port  78  may communicate with a timing mechanism (not shown) that automatically deflates balloon  82  after a predetermined time, e.g., 15 seconds, to ensure that cerebral blood flow is not inhibited for a period so long as to cause cerebral compromise.  
       FIGS. 4D-4E  illustrate mechanically deployable mechanism  92  comprising flexible wires  95  and impermeable coating  97  in contracted and deployed states, respectively. Impermeable coating  97  comprises an elastomeric polymer, e.g., latex, polyurethane or polyisoprene. The proximal end of deployable mechanism  92  is affixed to body  73 . The distal end of mechanism  92  is affixed to distalmost section  99 , which in turn communicates with sliding member  93  that is configured to slide longitudinally within a lumen of body  73 .  
      Upon actuating deployment knob  72 , i.e., proximally retracting knob  72  within slot  74 , sliding member  93  and distalmost section  99  are proximally retracted relative to body  73 , to compress flexible wires  95 . Impermeable coating  97  conforms to the shape of wires  95  to provide a plug-shaped occlusive member, as shown in  FIG. 4E . Deployment knob  72  may communicate with a timing mechanism (not shown) that automatically releases mechanism  92  after a predetermined time.  
      Referring to  FIG. 5 , alternative embodiments for guide wire  45  and balloon  46  of  FIG. 3A  are described for use in occluding a communicating artery, e.g., the external carotid artery. In  FIG. 5A , occlusive device  121  comprises proximal hub  120 , hypo tube  127 , shaft  128 , balloon  136  and coil  142 . Hypo tube  127  preferably comprises stainless steel, while shaft  128  preferably comprises a radiopaque material. Balloon  136  is configured using a tubular balloon material, e.g., chronoprene, that is compliant in nature and provides a self-centering balloon when deployed. The proximal end of balloon  136  is secured to radiopaque shaft  128  by band  132  and taper  130 . The distal end of balloon  136  is affixed to coil  142  via taper  140 .  
      Core wire  122  is slidably disposed within hypo tube  127  so that its proximal end and is disposed in proximal hub  120  and its distal end is affixed to taper  140 . Fluid may be injected into the annulus surrounding core wire  122  so that the fluid exits into balloon  136  via inflation window  134 , thus permitting balloon  136  to expand radially and longitudinally. Core wire  122 , taper  140  and coil  142  may move distally to accommodate such linear extension. Stroke limiter  123 , disposed on the distal end of core wire  122 , ensures that balloon  136  does not extend longitudinally more a predetermined distance ‘x’.  
      In the alternative embodiment of  FIG. 5B , occlusive device  151  comprises shaft  152 , balloon  158 , and coil  168 . Shaft  152  preferably comprises a radiopaque material and connects to a hypo tube similar to that of  FIG. 5A . The proximal components for device  151 , i.e., proximal to shaft  152 , are the same as the components that are proximal to shaft  128  in  FIG. 5A .  
      Balloon  158  is constrained at its proximal end by band  156  having proximal balloon marker  157 . Taper  154  is provided on the proximal end of band  156  in alignment with the proximal end of balloon  158 . The distal end of balloon  158  is everted, as shown in  FIG. 5B , and secured with radiopaque band  160  that provides a fluoroscopic reference for the distal boundary of the balloon. Taper  164  further secures the everted distal section, sandwiching between the first and second folds.  
      Core wire  150  is distally affixed to coil  168  having radiopaque marker  170 . Lumen  159  communicates with an inflation port (not shown) at its proximal end and with inflation window  136  at its distal end. Lumen  159  permits the injection of fluids, e.g., saline, to deploy balloon  158 . Core wire  150  is slidably disposed in the hypo tube and shaft  152  to prevent extension of balloon  158  up to a distance ‘x’, as indicated in  FIG. 5A .  
      Referring to  FIG. 6 , apparatus suitable for removing thrombi are described. In  FIG. 6A , thrombectomy wire  200  having ball  202  affixed to its distal end is depicted in a contracted state within coil  204 . In a preferred embodiment, thrombectomy wire  200  comprises a shape-memory retaining material, for example, a Nickel Titanium alloy (commonly known in the art as Nitinol).  
      The use of Nitinol generally requires the setting of a custom shape in a piece of Nitinol, e.g., by constraining the Nitinol element on a mandrel or fixture in the desired shape, and then applying an appropriate heat treatments, which are per se known.  
      Coil  204  covers wire  202  along its length, up to ball  202 . As coil  204  is retracted proximally, wire  200  self-expands to a predetermined knot configuration, as shown in  FIG. 6B . In a preferred embodiment, the diameter of wire  200  is about 0.002 inches, the diameter of ball  202  is about 0.014 inches, and coil  204  is manufactured using platinum. It should be appreciated that an outer sheath may be used in place of coil  204 , such that proximally retracting the outer sheath causes wire  200  to deploy.  
      Referring to  FIG. 6C , a method for using thrombectomy wire  200  to snare a thrombus T, e.g., in middle cerebral artery MCA, is described. Thrombectomy wire  200 , initially contracted within coil  204 , is advanced through a lumen of catheter  2 , then preferably is advanced in retrograde fashion via the internal carotid to the site of the cerebral lesion in the MCA. Under controlled flow conditions, i.e., conditions that will promote the flow of emboli toward catheter  2 , wire  200  and coil  204  pierce thrombus T, as shown in  FIG. 6C .  
      Coil  204  then is retracted proximally with respect to wire  200  to self-deploy shape memory wire  200  at a location distal to thrombus T, as shown in  FIG. 6D . Wire  200  then is retracted to snare thrombus T, and ball  202  of wire  200  facilitates removal of the lesion.  
      Referring to  FIGS. 6E-6F , an alternative embodiment a thrombectomy wire of FIGS.  6 A-B is described. In  FIG. 6E , thrombectomy wire  205  having distal ball  208  is delivered in a contracted state within slidable sheath  206 . Thrombectomy wire  205  is configured to self-deploy to a predetermined shape, e.g., via use of a shape memory material, upon proximal retraction of sheath  206 . Coil  207  overlays slidable sheath  206  and is affixed to ball  208  at points  209   a  and  209   b , e.g., via a solder or weld. Sheath  206  is initially provided in a distalmost position such that it abuts ball  208  and constrains wire  205  along its length. Sheath  206  advantageously enhances the distal pushability of the device, particularly when the device is advanced though an occlusion.  
      Upon positioning the distal end of wire  205  at a location distal to the occlusion, sheath  206  is retracted proximally to cause wire  205  to self-deploy to a knot-shaped configuration, as depicted in  FIG. 6F . Coil  207 , affixed to ball  208  of wire  205 , conforms to the shape of wire  205 . The deployed knot-shaped device then is proximally retracted to snare the occlusion, according to methods described hereinabove.  
      Referring to  FIGS. 7A-7E , alternative embodiments for thrombectomy wires in accordance with the present invention are depicted. In  FIG. 7A , thrombectomy wire  210  comprises a plurality of intersecting hoops that deploy upon retraction of a coil or sheath. Hoops  212  and  214  may be orthogonal to each other, as shown in  FIG. 7A . The hoops are designed to form a knot-shape to snare a thrombus in combination with ball  216 . Additionally, there may be a series of intersecting hoops, as shown in  FIG. 7B . Thrombectomy wire  220  comprises first knot  222  and second knot  224  separated by a distance ‘y’, although it will be obvious that any variation in the number of knots and their shapes are intended to fall within the scope of the present invention.  
      Referring to  FIG. 7C , thrombectomy wire  230  comprises spiral-shaped distal section  232 . The spiral shape is formed from a series of planar hoops, the diameter of hoops being slightly smaller with each successive hoop. As shown, the hoops of spiral  232  are depicted as being orthogonal to the main axis of wire  230 . Elbow  234  defines a bent section that connects main wire section  236  to first hoop  238 . As shown, elbow  234  is orthogonal to main wire section  236 , however, it may be provided at any angle. Similarly, as shown in  FIG. 7D , wire  240  may comprise a plurality of spiral-shaped sections  242  and  244  separated by a distance ‘z’.  
      In  FIG. 7E , thrombectomy wire  250  comprise a plurality of petal-shaped sections that deploy upon retraction of a coil or sheath. As shown, petal-shaped sections  252  and  254  are orthogonal to each other, however, they may be provided at any angle with respect to main axis  256  and each other, and any number of petal-shaped sections may be provided  
      Referring to  FIGS. 8A-8D , a further alternative thrombectomy device is illustrated. Device  260  removes a lesion by organizing the fibrin strands of the lesion around the deployable wires using a rotational motion. Exemplary method steps for using the embodiments described in  FIGS. 8A-8D  are described in  FIG. 10  hereinbelow.  
      In  FIG. 8A , thrombectomy device  260  comprises at least one deployable wire  262  affixed at its proximal and distal ends at points  266  and  264 , respectively. Deployable wire  262  is initially contracted within coil  268 , and when tubular member  268 , e.g., a coil or sheath, is retracted proximally, deployable wires  262  self-expand to a predetermined shape, as shown. As deployable wires  262  are rotated within the thrombus itself, the fibrin strands of the thrombus will become engaged with and wrap around deployable wires  262 .  
      In  FIG. 8B , alternative thrombectomy device  270  comprises at least one deployable wire  274  that is distally affixed to wire  270  at point  276 . The proximal end of wire  274  is secured to sliding member  272 , which slides longitudinally over wire  271 . When wire  271  and sliding member  272  move with respect to each other, deployable wire  274  either radially outwardly deflects, as shown, or flattens out for a contracted position.  
      In  FIG. 8C , thrombectomy device  280  comprises deployable wire  282  configured to form a plurality of loops  285  around shaft  283 . The distal end of deployable wire  282  is affixed to shaft  283  at point  284 , which may serve as an atraumatic tip for guiding the device and piercing the thrombus. The proximal end of deployable wire  282  is affixed to tube  281 . Tube  281  spans-the length of the device and has a proximal end that is manipulated by the physician. Distally advancing tube  281  over shaft  283  deploys loops  285 , as shown, while proximally retracting tube  281  with respect to shaft  283  contracts loops  285 . In the deployed state, rotating the device about its axis will cause loops  285  of wire  282  to engage the thrombus and wrap the fibrin strands about the device, as described in  FIG. 10  hereinbelow.  
      In  FIG. 8D , thrombectomy device  290  comprises a plurality of shape-memory, arrowhead-shaped wires  292  that are distally affixed to each other at point  294  and proximally affixed at junction  298 . Wires  292  are initially contracted within tubular member  296 , e.g., a coil or sheath, and upon proximal retraction of tubular member  296 , wires  292  self-deploy to the configuration shown.  
      Apparatus and methods for organizing fibrin strands of a thrombus around a thrombectomy device are further described with respect to  FIGS. 9 and 10 . In  FIG. 9A , thrombectomy device  300  comprises proximal segment  306 , catheter  302 , and distal segment  304 . Proximal segment  306  comprises thumb ring  308 , proximal body  310 , and deployment knob  312  that slides longitudinally within slot  314 . Distal segment  304  comprises at least one deployable wire  316  and atraumatic tip  318 .  
       FIG. 9B  provides a schematic view of distal segment  304 . Deployable wire  316  preferably comprises a shape memory material that communicates with deployment knob  312  at its proximal end, as described in  FIG. 9C  hereinbelow. The distal end of deployable wire  316  is affixed to atraumatic tip  318 , e.g., using a solder or weld. Deployable wire  316  is delivered in a contracted state, i.e., such that it does not substantially extend radially beyond catheter  302 . Upon actuation of deployment knob  312 , wire  316  self-expands via holes  317  to form a whisk-type element, as shown. Catheter  302  may be provided with one or more working lumens that communicate with delivery port  305  to permit the delivery of fluids, e.g., saline or other drugs that facilitate clot removal.  
       FIG. 9C  provides a schematic view of proximal segment  306 . The distal end of deployable wire  316  is configured to deploy from catheter  302 . The proximal end of catheter  302  is affixed to outer shaft  322 , which preferably has a square cross-section. Outer shaft  322  is keyed to inner shaft  320 . Inner shaft  320  is keyed to slidably more actuator  323 , so that rotational motion of one element causes rotation of the other. Catheter  302  further is affixed to retainer  315 , which permits catheter  302  to rotate freely relative to proximal body  310 .  
      Thumb ring  308  communicates with actuator  323  via joint  321 . Joint  321  permits rotational motion of actuator  323  with respect to thumb ring  308 . Actuator  323  is affixed to rotational member  326  at its distal end, which in turn is affixed to inner shaft  320 . Rotational member  326  comprises knob  327  that is configured to slidably rotate within groove  328  in the wall of body  310 .  
      Deployable wire  316  is deployed by sliding deployment knob  312  within slot  314 . Deployment knob  312  comprises a rounded pin that engages with a groove of ring  324 . This engagement distally advances ring  324  within slot  325  of catheter  302 . Deployable wire  316  is affixed to ring  324 , such that distally advancing ring  324  via deployment knob  312  allows wire  316  to self-deploy. The rounded pin engagement between knob.  312  and the groove of ring  324  further permits free axial rotation of ring  324  while knob  312  is stationary.  
      With wire  316  deployed, thumb ring  308  is depressed with a force that overcomes a resistance force provided by spring  330 . Depressing thumb ring  308  in turn causes rotational member  326  to be advanced distally via groove  328 . When a thumb force is no longer applied, the resistance of spring  330  then pushes rotating member  326  in a proximal direction via groove  328 . This in turn causes rotation of rotational member  326 , inner shaft  320 , outer shaft  322  and catheter  302 . The rotation of catheter  302  generates rotation of thrombectomy wire  316 .  
      The rotation of thrombectomy wire  316  may be clockwise, counterclockwise, or a combination thereof by manipulating the profile of groove  328 . The rotational speed may be controlled by varying the resistance of spring  330 , and the duration of rotation can be controlled by varying the length in which rotational member  326  can longitudinally move. Alternatively, another force transmission means, e.g., a motor, may be coupled to the proximal end to provide for controlled axial rotation of catheter  302 .  
       FIG. 10  illustrate method steps for removing thrombi using any of the thrombectomy devices described in  FIGS. 8-9 . In a first step, catheter  302  is advanced through catheter  2  of  FIG. 2 , then advanced in a retrograde fashion toward the occlusion. Catheter  302  may be advanced via the internal carotid artery to treat a lesion T located in a cerebral vessel V, e.g., the middle cerebral artery. Atraumatic tip  318  serves to protect vessel walls as catheter  302  is advanced through tortuous anatomy. At this time, flow control devices  8  of  FIG. 2  are deployed to cause retrograde blood to flow in the directions indicated.  
      Tip  318  of catheter  302  then is advanced to pierce thrombus T, as shown in  FIG. 10B . Deployment knob  312  of  FIG. 9  then is actuated to deploy at least one deployable wire  316  within thrombus T. Thumb ring  308  then is depressed, resulting in the controlled rotation of deployable wire  316 , such that the wire engages the fibrin strands of thrombus T. As the fibrin strands are wound about deployable wire  316 , the diameter of thrombus T decreases, as shown in  FIG. 10D . Blood flows in a retrograde fashion, i.e., toward catheter  2  which is positioned in the common carotid artery, and any emboli E generated during the procedure will be removed by the catheter in the process. It should be noted that deployable wire  316  is designed such that it does not contact the inner wall of vessel V. Once the thrombus T is sufficiently wound about deployable wire  316 , as shown in  FIG. 10E , catheter  302  may be retracted into catheter  2 .  
      Referring to  FIG. 11 , an alternative embodiment of the present invention is described wherein a second catheter is advanced to a location in closer proximity to the occlusive lesion. Main catheter  340  having distal occlusive element  342  is positioned, for example, in the common carotid artery, as described in  FIG. 2 . Recovery catheter  344  having distal occlusive element  346  and radiopaque marker  347  is configured to telescope within the lumen of main catheter  340 .  
      In a preferred method, main catheter  340  is disposed in the common carotid artery. Retrograde flow then is established using venous return line  52  of  FIG. 3A  according to methods described hereinabove. A  0 . 014  inch neuro guidewire  350  then is advanced via the lumen of main catheter  340  to the site of the cerebral occlusion, and neuro guidewire  350  is disposed distal to the lesion. In this illustration, an occlusion (not shown) would be located approximately within an interval ‘L’, e.g., in the middle cerebral artery. Recovery catheter  344  then is advanced distally over neuro guidewire  350  and is positioned proximal to occlusion ‘L’. Upon positioning recovery catheter  344 , occlusive distal element  346  is deployed.  
      Neuro catheter  348  then is advanced over neuro guidewire  350 , and the distal end of neuro catheter  348  is disposed at a location distal to occlusion ‘L’, as shown. Neuro guidewire  350  then is retracted proximally and removed from within neuro catheter  348 , which comprises a relatively small lumen. With neuro guidewire  350  removed, a thrombectomy wire is advanced distally through the lumen of neuro catheter  348 , and the thrombectomy wire takes the place of guidewire  350  in  FIG. 11 . Neuro catheter  348  then is proximally retracted, and thrombectomy wire  350  is deployed to treat the occlusion according to methods described hereinabove.  
      Recovery catheter  344  comprises at least one blood venting hole  345 . The established retrograde flow through catheter  344  using venous return line  52  induces retrograde flow in at least the internal carotid artery via blood venting hole  345 . Flow into venting hole  345  may be manipulated by actuating inner sheath  349 , e.g., by longitudinally sliding inner sheath  349  within catheter  344 , or rotating inner sheath  349  relative to its longitudinal axis.  
      Advantageously, the distal end of recovery catheter  344  is positioned in close proximity to the lesion, so that wire  348  and any emboli generated are immediately confined within recovery catheter  344 . Furthermore, advancing recovery catheter  344  via the internal carotid artery eliminates the need for deploying balloon  10  of  FIG. 2  in the external carotid artery.  
      Referring to  FIG. 12 , a further alternative embodiment of the present invention is described wherein a second catheter is advanced to a location in closer proximity to the occlusive lesion. Main catheter  360  having distal occlusive element  362  is positioned, for example, in the common carotid artery, as described in  FIG. 2 . Recovery catheter  364  comprises a wire weave configuration and may be manufactured using a shape memory material, e.g., Nitinol, as described hereinabove.  
      Recovery catheter  364  further comprises blood impermeable membrane  365 , such as latex, polyurethane or polyisoprene, that encloses the wire weave of recovery catheter  364 . The elastic properties of blood impermeable membrane  365  allow it to conform to the contracted and expanded states of recovery catheter  364 .  
      Recovery catheter  364  is advanced in a contracted state within outer sheath  366 . As described in applicants&#39; commonly assigned, co-pending application Ser. No. 09/916,349, which is herein incorporated by reference, outer sheath  366  is retracted proximally to cause occlusive distal section  368  to self-expand to a predetermined deployed configuration, as shown in  FIG. 12A . Occlusive distal section  368  may be sized for different vessels, e.g., the middle cerebral arteries, so that the distal end of recovery catheter  364  is disposed proximal to an occlusion, e.g., as depicted at location ‘L’. Mouth  369  provides a relatively large distal opening, i.e., flush with the inner wall of the targeted vessel.  
      Neuro catheter  370  then is advanced over neuro guidewire  372 , as described hereinabove in  FIG. 11 , and a thrombectomy wire is exchanged for neuro guidewire  372 . Neuro catheter  370  is proximally retracted, and thrombectomy wire  372  removes the occlusion at location ‘L’ according to methods described hereinabove. Upon removing the occlusion, thrombectomy wire  372  is retracted into mouth  369 , along with any emboli generated during the procedure.  
      It will be advantageous to collapse mouth  369  upon completion of the procedure, to prevent thrombi and/or emboli from exiting removal catheter  364 .  FIGS. 12B-12D  illustrate a method for effectively collapsing mouth  369  proximally to distally, as shown.  FIG. 12B  shows outer sheath  366  having radiopaque marker  367  in a proximally retracted position that allows occlusive distal section  368  to deploy. After directing thrombi and/or emboli into mouth  369 , outer sheath  366  is advanced distally to collapse mouth  369 , as shown sequentially in  FIGS. 12C-12D . This effectively confines thrombi and/or emboli within mouth  369 .  
      Referring now to  FIG. 13 , a method for using the apparatus described hereinabove to treat stroke, in accordance with principles of the present invention, is described. In  FIG. 13A , flow control devices  400  having controllers  402  are introduced into the patient&#39;s vasculature in a contracted state, e.g., via the radial or brachial arteries, and preferably are positioned in the patient&#39;s left subclavian artery and brachiocephalic trunk, as shown. It will be appreciated by those skilled in the art that varying the number of flow control devices and their placements is intended to fall within the scope of the present invention. Blood flow occurs in the directions indicated.  
      Referring to  FIG. 13B , catheter  404  of  FIG. 3A  is positioned in the common carotid artery CCA using guide wire  406 . Catheter  404  is positioned proximal to the carotid bifurcation, as shown, preferably in the hemisphere in which the cerebral occlusion is located. Balloon  408 , for example, as described in  FIG. 5 , then is disposed in the external carotid artery and deployed, as shown in  FIG. 13C .  
      Referring to  FIG. 13D , distal occlusive element  412  of catheter  404  is deployed to occlude antegrade flow in the selected CCA. Venous return catheter  52  of  FIG. 3A  then is placed in a remote vein, such that negative pressure in venous return catheter  52  during diastole establishes a continuous flow through the lumen of catheter  404 . This induces retrograde flow in the ICA, as depicted in  FIG. 13D . A thrombectomy wire  414 , for example, as described in  FIGS. 6-10 , is advanced through catheter  404  and into the cerebral vasculature via the ICA.  
      Referring to  FIG. 13E , a view of the cerebral vasculature under the conditions described in  FIG. 13D  is shown. Thrombectomy wire  414  has been advanced to a location just proximal to thrombus T, for example, in middle cerebral artery MCA.  
      At this time, flow control devices  400  then are deployed using controller  402  to form occlusive elements  420 , as shown in  FIG. 13F . As depicted, flow from aortic arch AA into brachiocephalic trunk BT and left subclavian artery SA are inhibited, which in turn inhibits flow into the vertebral arteries VA and right CCA, as shown. It will be apparent to those skilled in the art that occlusive elements  420  may be selectively placed at other locations to permit and/or inhibit flow into the selected locations of the cerebral vasculature.  
      The deployment of occlusive elements  420  controls flow in the Circle of Willis, as shown in  FIG. 13G . In this example, since arterial flow into the vertebral arteries VA and the right internal carotid artery has been inhibited, emboli that are generated will be directed in a retrograde fashion toward catheter  404  via the left internal carotid artery. The distal end of thrombectomy wire  414  then pierces thrombus T and deployable knot  416  is deployed distal to the thrombus, as shown in  FIG. 13G . Alternatively, other thrombectomy wire configurations may be used to treat the lesion, as described in  FIGS. 6-10 .  
      Deployable knot  416  of thrombectomy wire  414  snares thrombus T, as shown in  FIG. 13H , and subsequently is retracted into catheter  404 . Any emboli generated during the procedure will be directed into catheter  404  via the established retrograde flow. Occlusive elements  420 , distal occlusive element  412 , and external carotid occlusive device  408  then are contracted, and catheter  404  may be removed from the patient.  
      It should be noted that the method steps described in  FIG. 13  may be used in combination with any of the apparatus described hereinabove. For example, recovery catheters  344  and  364  of  FIGS. 11 and 12 , respectively, may be advanced through catheter  404  of  FIG. 13 . Additionally, any of the snaring thrombectomy devices of  FIG. 7  or the rotating thrombectomy devices of  FIG. 8  may be used in place of thrombectomy wire  414  as depicted. Similarly, any of the occlusive devices described in  FIGS. 4B-4E  and  FIGS. 5A-5B  may be used in place of occlusive elements  420  and  408 , respectively.  
      Referring to  FIGS. 14-16 , further apparatus and methods is accordance with principles of the present are described. In  FIG. 14A , catheter  430  may be configured for use in any of the carotid and vertebral arteries. Catheter  430  comprises blood intake port  432 , distal occlusive element  436  and radiopaque tip marker  435 . Occlusive element  436  comprises proximal and distal tapers  438  and  440 , respectively. Inner sheath  434  is configured for longitudinal sliding motion within catheter  430 .  
      Inner sheath  434  is initially provided in a distalmost position that covers blood intake port  432  in a closed state, as shown in  FIG. 14A . Deployment of occlusive element  436  inhibits antegrade blood flow in vessel V, at which time therapeutic drugs and/or devices may be delivered to site of the occlusion via lumen  437 .  
      Retrograde blood flow in vessel V is induced by placing venous return catheter  52  of  FIG. 3A  into a remote vein, according to methods described hereinabove. The retrograde flow through lumen  437  induces retrograde flow distal to occlusive element  436 . Distal taper  440  facilitates retrograde blood flow into lumen  437 .  
      If antegrade flow is desired, inner sheath  434  may be retracted proximally to expose blood intake port  432 , as shown in  FIG. 14B . This permits antegrade flow to enter intake port  432  and continue flowing in an antegrade direction distal to occlusive element  436 . Proximal taper  438  is configured to enhance antegrade blood flow into intake port  432 .  
      Cerebral flow manipulation may be enhanced by placing a first catheter in accordance with  FIG. 14  in a common carotid artery and a second catheter in a vertebral artery, each on the hemisphere of the occlusion.  FIG. 15  depicts apparatus suitable for controlling cerebral flow when utilizing one carotid and one vertebral catheter in combination. In  FIG. 15 , catheters  450  and  470  are configured to be disposed in the common carotid and vertebral arteries, respectively. However, it should be appreciated by those skilled in the art that two vertebral catheters may be used, i.e., one in each of the vertebral arteries, in combination with the carotid catheter.  
      Catheters  450  and  470  each comprises a plurality of lumens. Inner sheaths  456  and  476  are configured to slide longitudinally within an outermost lumen of their respective catheters. Inner sheaths  456  and  476  communicate with deployment knobs  452  and  472 . Sliding deployment knobs  452  and  472  within slots  454  and  474  controls movement of inner sheaths  456  and  476 , respectively.  
      Inflation ports  462  and  482  communicate with lumens of their respective catheters. Working lumens  458 ,  460 ,  478  and  480  provide each catheter with two working lumens, e.g., for advancing guide wires and thrombectomy wires, and may be provided with hemostatic valves, for example, Touhy-Borst connectors.  
      Biocompatible tubing  459  and  461  enable fluid communication between retrograde flow controller  465  and lumens of catheter  450  and  470 , respectively. Retrograde flow controller  465  further communicates with venous return line  52  of  FIG. 3A  via tubing  463 . Switch  467  of retrograde flow controller  465  permits tubing  459  and  461  to communicate with retrograde flow of tubing  463  singularly or in combination, or switch  467  may inhibit retrograde flow altogether. For example, when retrograde flow is induced in tubing  463  via venous return line  52 , either one of tubing  459  and  461 , both, or neither may experience retrograde flow based on the position of switch  467 .  
      The apparatus described in  FIG. 15  allow a physician to provide either retrograde, antegrade or hemostatic flow from two opposing cerebral locations, i.e., the carotid and vertebral arteries. The lumens of the vertebral and/or carotid catheters may be perfused with blood or saline under pressure to manipulate flow at selected cerebral locations. The apparatus further allows for the injection of therapeutic drugs and/or thrombectomy devices. Chilled blood or saline may be delivered via either of the carotid and vertebral catheters to induce mild hypothermia at selected cerebral locations, while drug agents may be used to selectively alter the pressure gradients.  
      Additionally, lytic agents may be delivered via either of the carotid or vertebral catheters to aid in the disintegration of the occlusion. Such lytic agents preferably are used in combination with the flow manipulation techniques in accordance with the present invention, to direct emboli resulting from the lytic process into the removal catheter(s).  
      Referring to  FIG. 16 , method steps are described to manipulate cerebral flow in a variety of ways using a combination of carotid and vertebral catheters. In  FIG. 16A , a first catheter  500  comprising occlusive element  502  and blood intake port  504  is disposed in the left common carotid artery CCA. Inner sheath  506  is provided in a distalmost position to prevent fluid from entering intake port  504 , and occlusive element  502  is deployed to occlude antegrade flow. Balloon  508 , e.g., as described in  FIG. 5 , then is deployed in the ECA.  
      Similarly, a second catheter  520  comprising occlusive element  522  and blood intake port  524  is disposed in the left and/or right vertebral artery VA. In this example, one catheter is shown. Inner sheath  526  is provided in a distalmost position to prevent fluid from entering intake port  544 , and occlusive element  522  is deployed to occlude antegrade flow.  
      Venous return line  52  of  FIG. 3A  then is placed in a remote vein, according to methods described hereinabove, and retrograde flow may be induced either in the ICA, VA, or both arteries based on switch  467  of  FIG. 15 . As depicted in  FIG. 16A , switch  467  is set to a position that permits retrograde flow to be induced in both the carotid and vertebral catheters.  
      At this time, any of the flow control devices described in  FIG. 4  optionally may be deployed to occlude flow in the opposing carotid and vertebral arteries, according to methods described hereinabove. In this example, this ensures that blood flow is controlled in the left hemisphere.  
      The retrograde flow from catheters  500  and  520  encourages blood flowing in the middle cerebral artery MCA to flow toward both catheters, as indicated by the arrows in  FIG. 16A . Thrombectomy wire  510  having deployable knot  512  then is advanced into the MCA via the ICA and snares thrombus T, according to methods described hereinabove. Emboli E generated during the procedure are directed toward either one of catheters  500  and  520  for removal. Advantageously, the use of two catheters in combination provides for improved aspiration of the targeted vessel, in this case, the MCA.  
      Referring to  FIG. 16B , deployable knob  472  of  FIG. 15  is proximally retracted to retract inner sheath  526  and expose intake port  524  of catheter  520 . Switch  467  of retrograde flow controller  465  is positioned for retrograde flow only through catheter  500 . This allows antegrade flow in vertebral artery VA to enter intake port  524  and continue flowing in an antegrade direction into basilar artery BA and toward the MCA via the path indicated. The combination of antegrade flow from the left VA and either antegrade or retrograde flow from the left ICA directs emboli E generated in the MCA to flow primarily into catheter  500 .  
      There are several other variations possible for manipulating flow in the cerebral vasculature, to more efficiently deliver therapeutic drugs and/or direct emboli into a removal catheter. For example, therapeutic drugs may be delivered to the MCA when switch  467  of  FIG. 15  inhibits venous flow into both catheters  500  and  520 , and each of blood intake ports  504  and  524  are closed. Therapeutic drugs may be delivered via either port  458  or  478  into the MCA, or mild hypothermia may be induced by introducing chilled blood or saline.  
      It should be appreciated that varying the settings of retrograde flow controller  465  and deployable knobs  452  and  472  may provide for any combination of antegrade, retrograde, or hemostatic flow in the carotid and vertebral arteries. There are too many flow combinations to illustrate, however, it is intended that therapeutic drugs, thrombectomy devices, cardioplegic and/or brain chilling agents may be delivered under a variety of controlled cerebral flow conditions. Additionally, a neuro guidewire and neuro catheter, as described in  FIGS. 11 and 12 A hereinabove, may be used in conjunction with thrombectomy wire  510  of  FIG. 16 .  
      While preferred illustrative embodiments of the invention are described above, it will be apparent to one skilled in the art that various changes and modifications may be made therein without departing from the invention. The appended claims are intended to cover all such changes and modifications that fall within the true spirit and scope of the invention.