Methods for intravascularly-induced neuromodulation

Abstract

Methods and apparatus are provided for intravascularly-induced neuromodulation using a pulsed electric field, e.g., to effectuate irreversible electroporation or electrofusion, necrosis and/or inducement of apoptosis, alteration of gene expression, changes in cytokine upregulation, etc., in target neural fibers. In some embodiments, the intravascular PEF system comprises a catheter having a pair of bipolar electrodes for delivering the PEF, with a first electrode positioned on a first side of an impedance-altering element and a second electrode positioned on an opposing side of the impedance-altering element. A length of the electrodes, as well as a separation distance between the first and second electrodes, may be specified such that, with the impedance-altering element deployed in a manner that locally increases impedance within a patient's vessel, e.g., with the impedance-altering element deployed into contact with the vessel wall at a treatment site within the patient's vasculature, a magnitude of applied voltage delivered across the bipolar electrodes necessary to achieve desired neuromodulation is reduced relative to an intravascular PEF system having similarly spaced electrodes but no (or an undeployed) impedance-altering element. In a preferred embodiment, the impedance-altering element comprises an inflatable balloon configured to locally increase impedance within a patient's vasculature. The methods and apparatus of the present invention may be used to modulate a neural fiber that contributes to renal function.

1 - 14 . (canceled) 
     
     
         15 . A method for intravascularly-induced neuromodulation, the method comprising:
 positioning a pair of bipolar electrodes within a patient's vasculature, the electrodes being spaced less than about 20 mm apart;   increasing impedance within the vasculature between the bipolar electrodes; and   delivering a pulsed electric field across the bipolar electrodes.   
     
     
         16 . The method of  claim 15 , wherein positioning a pair of bipolar electrodes within a patient's vasculature further comprises positioning the pair of bipolar electrodes within the patient's renal artery. 
     
     
         17 . The method of  claim 15 , wherein positioning a pair of bipolar electrodes within a patient's vasculature further comprises positioning an intravascular catheter having the bipolar electrodes within the patient's vasculature. 
     
     
         18 . The method of  claim 17 , wherein positioning an intravascular catheter having the bipolar electrodes further comprises positioning an intravascular catheter having an impedance-altering element positioned between the bipolar electrodes. 
     
     
         19 . The method of  claim 18 , wherein locally increasing impedance further comprises locally increasing impedance with the impedance-altering element. 
     
     
         20 . The method of  claim 19 , wherein locally increasing impedance with the impedance-altering element further comprises occluding blood flow in the vasculature with the impedance-altering element. 
     
     
         21 . The method of  claim 20 , wherein occluding blood flow in the vasculature with the impedance-altering element further comprises inflating a balloon impedance-altering element. 
     
     
         22 . The method of  claim 15 , wherein locally increasing impedance further comprises directing the pulsed electric field across a wall of the patient's vasculature between the bipolar electrodes. 
     
     
         23 . The method of  claim 15 , wherein delivering a pulsed electric field further comprises modulating a neural fiber that contributes to renal function. 
     
     
         24 . The method of  claim 23 , wherein modulating a neural fiber that contributes to renal function further comprises inducing an effect in the neural fiber chosen from the group consisting of irreversible electroporation, electrofusion, necrosis, apoptosis, gene expression alteration, cytokine upregulation alteration, and combinations thereof. 
     
     
         25 . The method of  claim 15  further comprising substantially centering the bipolar electrodes within the patient's vasculature prior to delivering the pulsed electric field. 
     
     
         26 . The method of  claim 19 , wherein locally increasing impedance with the impedance-altering element further comprises centering the bipolar electrodes within the patient's vasculature. 
     
     
         27 . The method of  claim 15  further comprising monitoring electroporation in tissue exposed to the pulsed electric field. 
     
     
         28 . The method of  claim 19 , wherein locally increasing impedance with the impedance-altering element further comprises expanding an insulative covering into contact with a wall of the vasculature via a mechanical activation member. 
     
     
         29 . The apparatus of claim  1 , wherein at least one of the pair of bipolar electrodes comprises a wound coil. 
     
     
         30 . A method for intravascularly-induced neuromodulation, the method comprising:
 positioning a pair of bipolar electrodes within a patient's vasculature, the electrodes spaced less than about 20 mm apart;   occluding blood flow within the patient's vasculature between the bipolar electrodes; and   delivering a pulsed electric field across the bipolar electrodes.