Balloon catheter method for reducing restenosis via irreversible electroporation

Abstract

Restenosis or neointimal formation may occur following angioplasty or other trauma to an artery such as by-pass surgery. This presents a major clinical problem which narrows the artery. The invention provides a balloon catheter with a particular electrode configuration. Also provided is a method whereby vascular cells in the area of the artery subjected to the trauma are subjected to irreversible electroporation which is a non-thermal, non-pharmaceutical method of applying electrical pulses to the cells so that substantially all of the cells in the area are ablated while leaving the structure of the vessel in place and substantially unharmed due to the non-thermal nature of the procedure.

1 . A method of reducing restenosis, comprising:
 inserting into a vessel of a human patient a balloon catheter comprised of a flexible elongated shaft comprising a distal end portion for insertion into a vessel, wherein the balloon catheter is comprised of:   a balloon positioned at the distal end portion;   a first electrode positioned at the distal end portion of the shaft, the first electrode being comprised of a conductive material which is flexible and generally conforms to an outer surface of the balloon during expansion of the balloon;   a second electrode positioned at a point relative to the first electrode so as to allow electrical current to flow between the electrodes and through vascular tissue to the first electrode, the second electrode being comprised of a conductive material which is flexible and conforms to an outer surface of the balloon during expansion of the balloon; and   providing electrical pulses to the electrodes for durations and in amounts sufficient to subject substantially all vascular cells in a target area of an artery to irreversible electroporation (IRE).   
   
   
       2 . The method of  claim 1 , wherein the first and second electrodes each encircle the balloon and are positioned on either side of the target area. 
   
   
       3 . The method of  claim 2 , wherein the first and second electrodes each have a helical configuration around the balloon and the electrodes are positioned so that electrical current flows between the electrodes and through the target area. 
   
   
       4 . The device of  claim 1 , wherein the first and second electrodes each have an elongated configuration along a proximal end of the balloon to a distal end of the balloon and the electrodes are positioned so that electrical current flows between the electrodes and through the target area. 
   
   
       5 . The method of  claim 1 , further comprising:
 administering an anti-restenosis drug; and   wherein the IRE is carried out using a voltage and a current with defined ranges over a defined period of time and in absence of drug being delivered into the vascular cells.   
   
   
       6 . The method of  claim 5 , wherein the anti-restenosis drug is selected from the group consisting of paclitaxel and vasculant and is administered locally to the target area; and
 wherein electrical power source provides electrical pulses having a voltage, current, and duration so as to avoid thermal damage to a target area and surrounding tissue while obtaining IRE on the target area.   
   
   
       7 . The method of  claim 6 , wherein the pulses have a duration of from 50 to 200 microseconds with a current in a range of from 2,000 V/cm to 6,000 V/cm and wherein the electrical power source is configured to apply between two and twenty-five pulses. 
   
   
       8 . A balloon catheter device for insertion into a vessel and reducing neointima, comprising:
 a flexible elongated shaft comprising a distal end portion for insertion into a vessel;   a balloon positioned at the distal end portion;   a first electrode positioned at the distal end portion of the shaft, the first electrode being comprised of a conductive material which is flexible and generally conforms to an outer surface of the balloon during expansion of the balloon;   a second electrode positioned at a point relative to the first electrode so as to allow electrical current to flow between the electrodes and through vascular tissue to the first electrode, the second electrode being comprised of a conductive material which is flexible and conforms to an outer surface of the balloon during expansion of the balloon;   an electrical power source which provides electrical pulses to the electrodes for durations and in amounts sufficient to subject substantially all vascular cells in an area of an artery to irreversible electroporation (IRE) before neointima occurs.   
   
   
       9 . The device of  claim 8 , wherein the first and second electrodes each encircle the balloon. 
   
   
       10 . The device of  claim 9 , wherein the first and second electrodes each have a helical configuration around the balloon. 
   
   
       11 . The device of  claim 8 , wherein the first and second electrodes each have an elongated configuration along a proximal end of the balloon to a distal end of the balloon. 
   
   
       12 . The device of  claim 8 , wherein the first and second electrodes are formed from electrically conductive ink drawn on the balloon. 
   
   
       13 . The device of  claim 8 , for use wherein the IRE is carried out using a voltage and a current with defined ranges over a defined period of time and in absence of drug being delivered into the vascular cells. 
   
   
       14 . The device of  claim 13 , wherein the electrical power source provides electrical pulses having a voltage, current, and duration so as to avoid thermal damage to a target area and surrounding tissue while obtaining IRE on the target area. 
   
   
       15 . The device of  claim 14 , wherein the electrical power source is designed to emit pulses wherein the pulses have a duration of from 50 to 200 microseconds. 
   
   
       16 . The device of  claim 8 , wherein electrical power source applies current in pulses. 
   
   
       17 . The device of  claim 16 , wherein the electrical power source is configured to apply pulses having a duration of from 50 to 200 microseconds. 
   
   
       18 . The device of  claim 17 , wherein the electrical power source is configured to apply pulses of a current in a range of from 2,000 V/cm to 6,000 V/cm. 
   
   
       19 . The device of  claim 18 , wherein the electrical power source is configured to apply between two and twenty-five pulses. 
   
   
       20 . The device of  claim 19 , wherein electrical power source is configured to apply 10 pulses for 100 microseconds each at a current of 3,800 V/cm.