Abstract:
Methods and devices provide for temporary partial aortic occlusion to achieve diversion of blood flow to the brain in patients suffering from cerebral ischemia. The device can include an expandable frame with a membrane mounted on a first portion of the frame. The membrane can have at least one opening. In some embodiments, the membrane has an outer region and an inner region, and an opening in the inner region. In use, the frame can expand to conform to the inner walls of the aorta and the membrane can at least partially occlude the aorta thereby increasing cerebral perfusion. The frame can include one or more anchors to aid in maintaining the device in position against the arterial blood flow pressure.

Description:
FIELD OF THE INVENTION 
     The present invention relates generally to devices and methods for providing temporary partial obstruction of aortic blood flow, with a resulting increase in cerebral blood flow. More particularly, the invention provides a device with a membrane for partially occluding an artery. 
     BACKGROUND 
     Stroke is a disruption of blood to a portion of the brain. The two main mechanisms are occlusion of a blood vessel (ischemic stroke) or hemorrhage of a blood vessel (hemorrhagic stroke). Ischemic stroke is significantly more common. Current state of the art treatment for ischemic stroke includes the injection of tissue plasminogen activator (tPA) within four hours of the event. Some evidence also points to a benefit from tPA out to 12 hours. Alternate therapies include mechanical dislocation or retrieval of the clot. These treatments are effective because the brain has significant collateral blood flow. Thus, when the primary blood supply to an area is disrupted, collateral flow provides some amount of oxygen to the affected tissue. The quantity is dependent on the size of the vessel obstructed, the location of the obstruction, blood oxygen level, and cerebral blood flow volume. The model for this situation is an area of dead tissue (infarction) that is dead and unrecoverable. Surrounding this tissue is the penumbra; a zone of oxygen depleted tissue. This tissue ranges from dying tissue through tissue experiencing insignificant oxygen level drops. Clearly within this continuum there exists tissue that is not dead but is not functioning due to oxygen deficit. Stroke intervention is thus intended to recover as much of the penumbra as possible, limiting the amount of tissue killed in the brain. 
     One solution to increasing the effectiveness of treatment is to increase the amount of oxygen delivered via collateral blood flow. Unlike some parts of the body, increasing blood pressure does not generally increase flow to the brain. A solution proposed in U.S. Pat. No. 6,743,196, to Barbut et al., is to insert a balloon into the aorta to partially occlude the aorta above the renal arteries as a means of increasing cerebral blood flow. Limitations of this device and method include mechanical complexity, constant monitoring requirements, and maintaining arterial access for the length of its use. Additionally, an inherent drawback with using a balloon to occlude a vessel is that balloons are always susceptible to failure (e.g., popping, leaking). 
     A device that is to be placed in an artery must address additional concerns compared to devices placed in veins because of the hemodynamic differences between arteries and veins. Arteries are much more flexible and elastic than veins and, in the arteries, blood flow is pulsatile with large pressure variations between systolic and diastolic flow. These pressure variations cause the artery walls to expand and contract. Blood flow rates in the arteries vary from about 1 L/min to about 5 L/min. 
     A need exists for a less complex, easily delivered, temporary arterial occlusion device that partially occludes an artery to increase cerebral blood flow, while avoiding the drawbacks of the prior devices. An associated filter that captures embolic material would be advantageous as well. 
     SUMMARY OF THE INVENTION 
     The present invention provides devices and methods for temporarily increasing cerebral blood flow. More specifically, a vascular occlusion, obstruction and/or constriction device is disclosed. The terms occlusion, obstruction, and constriction are used interchangeably herein to refer to partial or complete blockage of a vessel, and to any of the devices that provide such blockage. The devices include an occluding, obstructing, or constricting mechanism. In some embodiments, the devices include a filtration mechanism to trap emboli. The devices are collapsible and expandable to facilitate insertion into and removal from the vessel. 
     In one embodiment, the device includes an expandable frame with a membrane mounted on a first portion of the frame. The membrane has at least one opening. In some embodiments, the membrane has an outer region and an inner region, and an opening in the inner region. In use, the frame expands to conform to the inner walls of the aorta and the membrane at least partially occludes the aorta thereby increasing cerebral perfusion. The frame can include one or more anchors to aid in maintaining the device in position against the arterial blood flow pressure. 
     In another embodiment, the membrane is biodegradable such that upon insertion of the device, the membrane provides partial occlusion of the aorta to increase cerebral blood flow. As the membrane biodegrades, cerebral blood flow gradually returns to a normal state. The frame of the device can then be removed. 
     In a further embodiment, the expandable frame is a mesh tube with a membrane extending across at least part of a first end of the tube. In some embodiments, the second end of the tube is covered by a mesh or other filtering means. 
     In use, the expandable filter device is inserted into the aorta and expanded such that the membrane extends across the aorta to partially occlude the aorta and increase cerebral blood flow. In some embodiments, the membrane is at least partially permeable to blood. In other embodiments, the membrane has an opening to allow a limited amount of blood flow through the device. In one embodiment, the opening is sized to receive a catheter, and the downstream end of the device has one or more openings sized to receive a catheter. A catheter can traverse the filter device to provide access to arteries and organs upstream of the filter device. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows an embodiment of a filter device according to the present invention. 
         FIGS. 2-4  show additional embodiments of filter devices according to the present invention. 
         FIG. 5  shows a filter device according to the present invention in place in a vessel. 
     
    
    
     DETAILED DESCRIPTION 
     The filter devices disclosed herein are characterized by their ability to withstand high arterial blood flow rates for an extended time and their ability to expand and contract with the wall of the aorta. In some embodiments, the devices are made of a material that is impermeable to blood such as TEFLON (polytetrafluoroethylene) or nitinol. The devices can have an anti-thrombogenic coating, such as heparin or Carmeda®. BioActive Surface (Carmeda Inc., U.S.). In other embodiments, the devices are made of a material that is permeable to blood, such as a mesh, woven material, or a thin polymer. All or a part of the device can be made of a biodegradable material. The device is collapsible and expandable and can be delivered surgically, endoscopically, or percutaneously with cannulas or intravascular catheters. In one embodiment, the device is introduced through the femoral artery. In another embodiment, the device is introduced through the brachial artery. 
     The device can be left in the aorta permanently or the device can be removed after temporary placement. In addition to or instead of a friction fit of an expandable frame, the device can include one or more anchoring mechanisms, such as sutures, surgical clips, hooks, loops, spikes, pins, or adhesives. The device can be of any shape, such as conical, frustoconical, ogival, cylindrical, hemispherical, or modifications of such shapes. The device can be self-expanding or is can be expanded mechanically such as by a balloon. Self-expanding devices can be made of a shape memory metal such as nitinol. In one embodiment, the device is flexible and expandable to fit a variety of vessel sizes. In another embodiment, the device is sized for a specific vessel. Multiple devices of varying sizes can be packaged together. 
     The method of the invention involves the temporary partial occlusion of arterial blood flow and resulting diversion of blood flow to the brain. The device of the invention is inserted into the aorta at or below the aortic arch and above the femoral arteries. In one embodiment, the device is placed in the aorta in the region of the renal arteries. In another embodiment, the device is placed in the aortic arch below the common carotid artery and braciocephalic trunk. In a further embodiment, the device is placed in the celiac trunk. In a still further embodiment, the device can be placed in the vena cava. 
     A membrane covering at least part of a first portion of the device serves to partially occlude the vessel. In some embodiments, the membrane is at least partially permeable to blood. The level of permeability and/or surface area that is permeable to blood can be adjusted to vary the amount of occlusion and thus vary the amount of blood flow diverted to the brain. In other embodiments, the membrane has one or more openings. In these embodiments, the membrane may or may not be partially permeable to blood. The number and size of the openings can be varied to determine the amount of blood flow diverted to the brain. 
     In a first embodiment, a filter device for temporary partial occlusion of an artery is provided as shown in  FIG. 1 . The device  10  includes a frame  20  having a first portion  12  and a second portion  14 , and a membrane  30  disposed over the first portion  12 . The membrane  30  is attached to the frame  20  by any suitable means including sonic or laser welding or adhesive bonding. In some embodiments, the membrane  30  is at least partially permeable to blood. The membrane  30  can be biodegradable. In some embodiments, the biodegradable material is selected to degrade over a desired time range from a very short time to a very long time after the device is inserted. In one embodiment, the membrane  30  biodegrades upon contact with an enzymatic agent, wherein the enzymatic agent is injected to degrade the membrane after the patient&#39;s cerebral blood flow returns to a substantially normal level. In another embodiment, the membrane biodegrades when irradiated, wherein the membrane is irradiated after the patient&#39;s cerebral blood flow returns to a substantially normal level. In one embodiment, the membrane  30  is made of polyglycolide. In another embodiment, the membrane  30  is a thin membrane with one or more laser-cut holes to allow blood flow. The thin membrane can be made of poly(dioxanone). In the embodiment shown in  FIG. 1 , the membrane  30  has a single opening  40  substantially centrally located. Alternatively, the opening  40  can be located off-center, or the membrane can have multiple openings. The number, size and position of openings  40  in the membrane  30  are selected to achieve a desired amount of blood flow diversion to the brain. 
     In some embodiments, the frame  20  includes multiple support members, such as struts  50 . The struts  50  can be compressible, expandable, or flexible. The frame  20  is at least partially expandable to conform to the lumen of a vessel. In one embodiment, the frame  20  is made of a super elastic material such as nitinol. In other embodiments, the frame  20  is made of titanium, TEFLON (golytetrafluoroethylene), stainless steel, ceramic, polymers, or mixtures of such materials. In still further embodiments, the frame  20  is made of a mesh or woven material. In some embodiments, the second, or downstream, portion of the frame  20  forms a filter to capture emboli and/or fragments of the biodegradable membrane. 
     In another embodiment, shown in  FIG. 3 , the device  200  has a frame  220  and a membrane  230  with an opening  240  in the membrane  230 . The frame  220  is a mesh tube  270  with a firstportion  212  and a second portion  214 . In a still further embodiment, shown in  FIG. 4 , a device  300  has a frame  320 , a membrane  330  and anchors  360 . The frame  320  has a first portion  312  and a second portion  314  and the frame  320  is solid with an opening  380  in the second portion  314  of the frame  320 . In embodiments with an open frame structure, such as those shown in  FIGS. 1-3 , the frame can be covered with a permeable material (for example, permeable material  400  on frame  20 ), such as a mesh, netting, or membrane to provide an additional filtration mechanism. In some embodiments, a permeable material covering the frame provides an additional mechanism to increase the occlusion of the artery and increase the blood flow to the brain. 
     In devices having a tapered, angled, or cone shape, such as those shown in  FIGS. 1 ,  2 , and  4 , at least the first end  12 ,  112 ,  312 , is expandable. In one embodiment, shown in  FIG. 2 , the device  100  includes a frame  120  with struts  150 , the frame  120  having a first portion  112  and a second portion  114 . The frame  120  includes a flexible or expandable band or ring  190  on the first portion  112 . The flexible ring  190  can aid in attaching the membrane  130  to the frame  120 , and the membrane  130  has an opening  140 . In another embodiment, the flexible ring  190  is attached to the frame  120  and the membrane  130  is attached to the ring  190 . 
     One or more anchors  160  can be included to aid in securing the device in the vessel. The anchors  160  can be hooks, spikes, loops, pins or any other protrusion sufficient to secure the device in the vessel. In one embodiment, the anchors  160  are mechanically retractable. In another embodiment, the anchors  160  are made of a deformable, flexible, or super elastic material, and are removable from a vessel wall by compressing or folding the frame  20 . The anchors  160  can be attached to the frame  20 , struts  50 , ring  190 , or permeable material  400 . 
       FIG. 5  shows a partial occlusion device  510  in place in the aorta. The device  510  includes a frame  520  made up of struts  550 . The frame  520  has a first portion  512  and a second portion  514 , and the first portion  512  of the frame  520  is covered by a membrane  530  with a central opening  540 . Anchors  560  extend from the first portion  512  of the frame  520  into the vessel walls  500  to secure the device  510  against blood flow, which is indicated by the arrow. 
     A mixture of carbon dioxide and oxygen (CO 2 /O 2 ) can be administered to the patient before, during, or after insertion of the filter device to provide additional blood flow to the brain. Enriching the blood content of CO 2  while maintaining a high oxygen level causes blood to be shunted to the brain. 
     Although the foregoing invention has, for the purposes of clarity and understanding, been described in some detail by way of illustration and example, it will be obvious that certain changes and modifications may be practiced with will still fall within the scope of the appended claims. Moreover, it will be understood that each and every feature described for any given embodiment or in any reference incorporated herein, can be combined with any of the other embodiments described herein.