Irreversible electroporation device and method for attenuating neointimal formation

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 .- 20 . (canceled) 
     
     
         21 . A method of ablating tissue cells in a blood vessel, comprising:
 identifying a target area of the blood vessel of a subject;   positioning a plurality of electrodes near the target area;   applying a plurality of electrical pulses through the positioned electrodes in an amount which is sufficient to subject tissue cells in the blood vessel target area to non-thermal irreversible electroporation (NTIRE); and   determining a clinical endpoint based on an electrical current flowing through the target area.   
     
     
         22 . The method of  claim 21 , wherein the step of determining comprises determining the clinical endpoint based on a change in conductance of the electrical current. 
     
     
         23 . The method of  claim 21 , wherein the step of determining comprises determining the clinical endpoint based on a decrease in conductance of the electrical current. 
     
     
         24 . The method of  claim 21 , wherein the step of determining comprises determining the clinical endpoint when a conductance of the electrical current is below the conductance at the beginning of the pulse application. 
     
     
         25 . The method of  claim 21 , further comprising:
 monitoring the electrical current flow while the plurality of electrical pulses are being applied; and   changing based on the monitored current flow at least one or more of pulse width, number of pulses and voltage.   
     
     
         26 . The method of  claim 21 , wherein:
 the number of electrodes is three or greater; and   the step of applying comprises energizing all electrodes simultaneously.   
     
     
         27 . The method of  claim 21 , wherein:
 the number of electrodes is three or greater; and   the step of applying comprises selectively switching the electrodes.   
     
     
         28 . The method of  claim 27 , wherein the step of applying comprises energizing the electrodes one pair at a time. 
     
     
         29 . The method of  claim 21 , wherein the step of positioning comprises positioning the plurality of electrodes near a point of surgical incision of a by-pass surgery. 
     
     
         30 . A method of reducing neointima in a blood vessel, comprising:
 identifying a target area of the blood vessel of a subject that is partially blocked;   positioning a plurality of electrodes near the identified target area;   applying a plurality of electrical pulses through the positioned electrodes in an amount which is sufficient to subject tissue cells in the blood vessel target area to non-thermal irreversible electroporation (NTIRE); and   monitoring an electrical current flow while the plurality of electrical pulses are being applied; and   determining a clinical endpoint based on a change in conductance of the monitored current flow.   
     
     
         31 . The method of  claim 30 , wherein the step of determining comprises determining the clinical endpoint based on a decrease in conductance of the electrical current. 
     
     
         32 . The method of  claim 30 , wherein the step of determining comprises determining the clinical endpoint when a conductance of the electrical current is below the conductance at the beginning of the pulse application. 
     
     
         33 . The method of  claim 30 , further comprising:
 changing a parameter selected from the group consisting of pulse width, number of pulses and voltage based on monitored current flow.   
     
     
         34 . The method of  claim 30 , wherein:
 the number of electrodes is three or greater; and   the step of applying comprises energizing all electrodes simultaneously.   
     
     
         35 . The method of  claim 30 , wherein:
 the number of electrodes is three or greater; and   the step of applying comprises selectively switching the electrodes.   
     
     
         36 . The method of  claim 35 , wherein the step of applying comprises energizing the electrodes one pair at a time. 
     
     
         37 . The method of  claim 30 , wherein the step of positioning comprises positioning the plurality of electrodes near a point of surgical incision of a by-pass surgery.