Irreversible electroporation device and method for attenuating neointimal

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 device and 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 neointima, comprising:
 identifying a target area of an artery of a subject that is partially blocked;   performing a procedure on the blocked target area to unblock the artery in a manner which increases blood flow through the target area of the artery; and   subjecting vascular cells of the target area of the artery to irreversible electroporation (IRE) before neointima occurs in the target area of the artery.   
   
   
       2 . The method of  claim 1 , wherein the procedure is balloon angioplasty and the IRE is performed without substantial damage to extra-cellular matrix components of the artery. 
   
   
       3 . The method of  claim 1 , wherein the balloon angioplasty and the IRE are carried out during a single surgical procedure. 
   
   
       4 . The method of  claim 1 , wherein the procedure is by-pass surgery and the target area comprises a point of surgical incision. 
   
   
       5 . The method of  claim 4 , wherein the by-pass surgery and the IRE are carried out during a single event and substantially all smooth muscle cells of the target area are irreversibly electroporated. 
   
   
       6 . The method of  claim 1 , wherein the IRE is carried out using a voltage and a current within defined ranges over a defined period of time and in absence of drug being delivered into the vascular cells and further wherein substantially all vascular cells are irreversibly electroporated. 
   
   
       7 . The method of  claim 6 , wherein the IRE is carried out within voltage, current, and time ranges so as to avoid thermal damage to the target area and surrounding tissue leaving tissue scaffolding substantially undamaged. 
   
   
       8 . The method of  claim 3 , wherein the angioplasty is carried out by:
 inserting a balloon catheter into a vessel of the patient; and   positioning electrodes of the catheter at the target site to carry out the IRE and applying current in pulses wherein the pulses have a duration of from 50 to 200 microseconds.   
   
   
       9 . The method of  claim 2 , wherein IRE is carried out immediately following the balloon angioplasty and from 5 to 20 pulses are administered. 
   
   
       10 . The method of  claim 1 , wherein the IRE is carried out prior to the step of performing a procedure on the blocked target area. 
   
   
       11 . A method of reducing restenosis, comprising:
 diagnosing a subject as suffering from artery disease;   performing balloon angioplasty on a target area of an artery of the subject;   positioning electrodes at the target area; and   applying controlled electrical pulses to the target area and subjecting the cells of the target area to irreversible electroporation (IRE) before restenosis occurs wherein the IRE is carried out without structural damage to extra-cellular tissue of the target area.   
   
   
       12 . The method of  claim 11 , wherein the balloon angioplasty and the IRE are carried out during a single surgical procedure. 
   
   
       13 . The method of  claim 12 , wherein the IRE is carried out using a voltage and a current with defined ranges over a defined period of time at a level which avoids thermal damage to the artery thereby leaving elastin and collagen substantially unchanged relative to before the IRE. 
   
   
       14 . The method of  claim 11 , wherein the IRE is carried out within voltage, current, and time ranges so as to avoid thermal damage to the target area and surrounding tissue and further wherein the balloon angioplasty and IRE are carried out during one surgical event. 
   
   
       15 . The method of  claim 14 , further comprising:
 inserting a catheter into a vessel of the patient; and   positioning the catheter at the target site to carry out the IRE.   
   
   
       16 . The method of  claim 14 , wherein current is applied in a plurality of pulses. 
   
   
       17 . The method of  claim 16 , wherein the pulses have a duration of from 50 to 200 microseconds. 
   
   
       18 . The method of  claim 17 , wherein the pulses apply a current in a range of from 2,000 V/cm to 6,000 V/cm. 
   
   
       19 . The method of  claim 16 , wherein between two and twenty-five pulses are applied. 
   
   
       20 . The method of  claim 16 , wherein 10 pulses are applied for 100 microseconds each at a current of 3,800 V/cm.