APPARATUS FOR LOCALISING AN ELECTRICAL FIELD

Abstract

An apparatus for localising an electrical field for electroporation of abluminal tissue such as ganglionated plexi is provided comprising a pulsed DC electrical power supply and at least two catheters. Each catheter includes at least one catheter tip and electrode assembly configured for endocardial placement such that the electrodes are positionable at separate endocardial locations and allow development of an electrical field between the electrodes to effect electroporation of the abluminal tissue in the electrical field.

Claims

1. An electrophysiology apparatus comprising a high voltage pulsed direct current (DC) supply and at least two catheters configured for endocardial access, each of the at least two catheters including at least one catheter tip and electrode assembly connectable with the high voltage pulsed DC supply to provide the at least two catheters with oppositely charged electroporation electrodes, wherein each of the at least two catheters is configured to be inserted into a different natural lumen or cavity adjacent to a target tissue at an abluminal location such that, in use, the at least two catheters at the different natural lumens or cavities create a peak cumulative electric field at the abluminal location between the oppositely charged electroporation electrodes to effect electroporation of the target tissue.

2. The electrophysiology apparatus of claim 1, wherein the electrophysiology apparatus comprises three catheters configured for endocardial access, each of the three catheters including at least one catheter tip and electrode assembly connectable with the high voltage pulsed DC supply to provide selectively at least two of the catheters with oppositely charged electroporation electrodes.

3. The electrophysiology apparatus of claim 1 or claim 2, wherein each catheter comprises a plurality of catheter tip and electrode assemblies connectable with the high voltage pulsed DC supply to provide the electroporation electrodes.

4. The electrophysiology apparatus of any one of the preceding claims wherein each catheter tip and electrode assembly comprises at least two electroporation electrodes.

5. The electrophysiology apparatus of any one of the preceding claims, wherein the electroporation electrodes are operable individually, in selected combinations, or together at the same time.

6. The electrophysiology apparatus of any one of the preceding claims wherein one or more of the electroporation electrodes are partially insulated circumferentially to direct the electric field in a desired direction and reduce the effect of the electric field in other directions.

7. The electrophysiology apparatus of any one of the preceding claims, comprising a sheath for electrical field blocking, wherein the sheath is configured to fit over one or more of the catheter tip and electrode assemblies and to have a plurality of openings for selective electric field emission.

8. The electrophysiology apparatus of claim 7, wherein the sheath is adjustable circumferentially or longitudinally upon the one or more catheter tip and electrode assemblies to influence electrical field emission.

9. The electrophysiology apparatus of claim 7 or claim 8, wherein the sheath comprises a metal reinforced polymer.

10. The electrophysiology apparatus of claim 4, wherein one or more of the catheter tip and electrode assemblies comprises an articulated catheter tip portion to allow one of the at least two electroporation electrodes on the catheter tip and electrode assembly to be deflected and re-oriented with respect to another of the at least two electroporation electrodes on the catheter tip and electrode assembly.

11. The electrophysiology apparatus of any one of the preceding claims, wherein the electrodes of each catheter tip and electrode assembly are individually controllable by a controller operable by a user, or by a programmable control system incorporating a controller, wherein said controller selectively controls the pairing of (+) and () electrodes of the catheter tip and electrode assemblies according to a switching sequence, and controls the duration of an electrical field pulse delivered by the high voltage pulsed DC supply.

12. The electrophysiology apparatus of any one of the preceding claims, wherein the high voltage pulsed DC supply has an operable range of from 500 to 2000 Volts, and is controllable to deliver an electrical field pulse duration of from 1 microsecond to 1 millisecond.

13. The electrophysiology apparatus of any one of the preceding claims, wherein the electroporation electrodes of respective catheters are positioned within an operational space of maximum width dimension in a range of 4 to 8 cm, and a (+) electrode is spaced from a coupling electrode by at least 2 mm.

14. The electrophysiology apparatus of any one of the preceding claims, wherein one or more of the at least two catheters is configured to effect temperature treatments and comprises an elongate tubular body having a proximal end and a distal end, and internal fluid channels, the distal end of the catheter having spaced electrodes on a side surface, and a recess between the electrodes, wherein the recess houses an inflatable balloon in communication with the internal fluid channels for receiving and venting a temperature control fluid, such as heated or cooled saline circulated under pressure control for selective inflation of the inflatable balloon.

15. The electrophysiology apparatus of any one of the preceding claims, wherein the target tissue comprises ganglionated plexi.

16. A system for carrying out electroporation of tissue comprising an electrophysiology apparatus as claimed in any one of claims 1 to 15 and a controller operably connected to the high voltage pulsed DC supply for selectively controlling the electroporation electrodes according to a switching sequence, and controlling the duration of an electrical field pulse delivered by the high voltage pulsed DC supply.

17. An electrophysiology apparatus according to any one of claims 1 to 15 for use in inhibiting atrial fibrillation of the heart.

18. An electrophysiology apparatus for use in inhibiting atrial fibrillation of the heart, wherein the electrophysiology apparatus comprises a high voltage pulsed direct current supply and at least two catheters configured for endocardial access, each catheter including at least one catheter tip and electrode assembly connectable with the high voltage pulsed DC supply to provide the at least two catheters with oppositely charged electroporation electrodes, wherein in use each of the at least two catheters is inserted into a different natural lumen or cavity adjacent to a target tissue at an abluminal location such that the at least two catheters at the different natural lumens or cavities create a peak cumulative electric field at the abluminal location between the oppositely charged electroporation electrodes to effect electroporation of the target tissue.

19. The electrophysiology apparatus for use of claim 18, wherein the target tissue comprises ganglionated plexi.

20. The electrophysiology apparatus for use of any one of claims 17 to 19, wherein electroporation is effected in an operational space including the ganglionated plexi and the electroporation electrodes of the at least two catheters have at least 2 mm of spacing therebetween, optionally at least 5 mm of spacing therebetween.

21. The electrophysiology apparatus for use of any one of claims 17 to 20, wherein electroporation is conducted upon aortocaval ganglionated plexi and the electroporation electrodes of the at least two catheters are positioned between the superior vena cava and the aortic root, superior to the right pulmonary artery.

22. The electrophysiology apparatus for use of claim 21, wherein electroporation is effected in an operational space including the ganglionated plexi and an inferior aspect of the operational space is positioned at least 2 mm above the transverse pericardial sinus, and optionally no more than 20 mm above the transverse pericardial sinus.

23. The electrophysiology apparatus for use of claim 18, wherein electroporation is effected in an operational space including the ganglionated plexi by means of at least three catheters, each of the three catheters including at least one catheter tip and electrode assembly configured for endocardial access comprising electroporation electrodes connectable with the high voltage pulsed DC supply to provide selectively at least two of the catheters with oppositely charged electroporation electrodes, the oppositely charged electroporation electrodes of the at least two catheters having at least 2 mm of spacing therebetween, optionally at least 5 mm of spacing therebetween.

24. The electrophysiology apparatus for use of any one of claims 17 to 23, wherein the electrodes of the respective at least two catheters are selectively controllable to change at least one of applied voltage, pulse duration, coupling between the electroporation electrodes, and charge polarity.

25. The electrophysiology apparatus for use of any one of claims 18 to 24, wherein one or more of the at least two catheters is manipulated to change electrical field direction by means of a fenestrated sheath movable axially and/or rotationally upon the catheter.

26. The electrophysiology apparatus for use of any one of claims 18 to 25, wherein each catheter tip and electrode assembly comprises at least two electroporation electrodes and one or more of the catheter tip and electrode assemblies is manipulated to change electrical field direction by means of the catheter tip and electrode assembly having a flexible portion or articulation point that allows one of the at least two electroporation electrodes on the catheter tip and electrode assembly to be deflected and re-oriented with respect to another of the at least two electroporation electrodes on the catheter tip and electrode assembly.

27. A method of inhibiting atrial fibrillation of the heart by electroporation of target abluminal tissue, the method comprising: introducing at least two catheters configured for endocardial access endocardially via a lumen of a natural vessel selected from any of the superior vena cava, the aorta, pulmonary arteries and coronary arteries, to locate the at least two catheters adjacent to the of target abluminal tissue, wherein each of the at least two catheters includes at least one catheter tip and electrode assembly, providing a high voltage pulsed direct current supply connected to the catheter tip and electrode assemblies to provide the at least two catheters with oppositely charged electroporation electrodes, generating a pulsed electrical field around the catheter tip and electrode assemblies adjacent to the of target abluminal tissue, and applying repeated pulses of the electrical field to effect electroporation of the of target abluminal tissue.

28. The method of claim 27, wherein the target abluminal tissue comprises neuronal tissue.

29. The method of claim 28, wherein of target abluminal tissue comprises ganglionated plexi.

30. The method of claim 29, wherein electroporation is effected in an operational space including the ganglionated plexi and the electroporation electrodes of the at least two catheters have at least 2 mm of spacing therebetween, optionally at least 5 mm of spacing therebetween.

31. The method of claim 29 or claim 30, wherein the electroporation is conducted upon aortocaval ganglionated plexi and the electroporation electrodes of the at least two catheters are positioned between the superior vena cava and the aortic root, superior to the right pulmonary artery.

32. The method of claim 31, wherein electroporation is effected in an operational space including the ganglionated plexi and an inferior aspect of the operational space is positioned at least 2 mm above the transverse pericardial sinus, and optionally no more than 20 mm above the transverse pericardial sinus.

33. The method of claim 29, wherein electroporation is effected in an operational space including the ganglionated plexi by means of at least three catheters, each of the at least three catheters including at least one catheter tip and electrode assembly configured for endocardial access comprising electroporation electrodes connectable with the high voltage pulsed DC supply to provide selectively at least two of the catheters with oppositely charged electroporation electrodes, the oppositely charged electroporation electrodes of the at least two catheters having at least 2 mm of spacing therebetween, optionally at least 5 mm of spacing therebetween.

34. The method of any one of claims 27 to 33, wherein the electrodes of the respective at least two catheters are selectively controllable to change at least one of applied voltage, pulse duration, coupling between the electroporation electrodes, and charge polarity.

35. The method of any one of claims 27 to 34 wherein one or more of the at least two catheters is manipulated to change electrical field direction by means of a fenestrated sheath movable axially and/or rotationally upon the catheter.

36. The method of any one of claims 27 to 35 wherein each catheter tip and electrode assembly comprises at least two electroporation electrodes and one or more of the catheter tip and electrode assemblies is manipulated to change electrical field direction by means of the catheter tip and electrode assembly having a flexible portion or articulation point that allows one of the at least two electroporation electrodes on the catheter tip and electrode assembly to be deflected and re-oriented with respect to another of the at least two electroporation electrodes on the catheter tip and electrode assembly.

Description

[0061] The disclosed methods and apparatus will now be further described with reference to the accompanying drawings in which:

[0062] FIG. 1 illustrates use of a loop shaped catheter tip with multiple electrodes positioned upon the loop shaped tip, wherein one such catheter (+) is positioned in the aorta, and the second () is positioned in the superior vena cava;

[0063] FIG. 2 illustrates use of several loop shaped catheter tips with multiple electrodes positioned upon the loop shaped tip, wherein one such catheter tip is positioned in the aorta, another catheter tip is positioned in the superior vena cava, and a further catheter tip is positioned in the right pulmonary artery.

[0064] FIGS. 3a to 3c illustrates schematically use of three catheter mounted electrodes arranged in proximity to the ganglionated plexi and operated as opposed charge pairs in a progressive electroporation sequence for effecting ablation of tissue;

[0065] FIG. 4 illustrates schematically use of a three electrodes (+), (+), () assembly in a higher field density ablation treatment;

[0066] FIG. 5 illustrates schematically use of a three electrodes (+), (+), () assembly in a variable electrical field geometry ablation treatment;

[0067] FIG. 6 illustrates examples of selected sites for positioning of catheter mounted electrodes for electroporation of the aortic root ganglionated plexi;

[0068] FIG. 7 illustrates schematically simultaneous heating of a fat pad including ganglia, with cooling of the myocardium;

[0069] FIG. 8 illustrates schematically electroporation of the heated fat pad and ganglia after heating and cooling as illustrated in FIG. 7;

[0070] FIG. 9 illustrates schematically a sheath wherein there is a circular aperture;

[0071] FIG. 10 illustrates schematically a sheath wherein there is rectangular aperture;

[0072] FIG. 11 represents a partially cutaway view of a braided sheath;

[0073] FIG. 12 illustrates schematically a catheter tip and electrode assembly positioned within an apertured sheath exposing electrical field emission from an electrode;

[0074] FIG. 13 illustrates schematically a straight linear catheter tip and electrode assembly;

[0075] FIG. 14 illustrates schematically a bifurcated linear catheter tip and electrode assembly;

[0076] FIG. 15 illustrates schematically a curvilinear catheter tip and electrode assembly.

[0077] FIG. 16 illustrates schematically a portion of a tubular electrode to be fitted over a catheter and showing an optional irrigation hole for transmission of fluid;

[0078] FIG. 17 illustrates a longitudinal section through the portion of a tubular electrode illustrated in FIG. 16

[0079] FIG. 18 illustrates schematically a portion of a catheter tip and electrode assembly which is partially insulated, optionally with an inflatable envelope or balloon; and

[0080] FIG. 19 shows a transverse section across the portion of a catheter tip and electrode assembly illustrated in FIG. 18.

EXAMPLE 1

[0081] Apparatus for Use in Treating the Aortocaval Ganglionated Plexi

[0082] In an embodiment intended for treating the aortocaval ganglionated plexi using at least two electroporation electrodes of opposite charge, which is located epicardially between the superior vena cava and the aortic root, superior to the right pulmonary artery, the operational space including target tissue may be of maximum width dimension in the range of 4 to 8 cm, for example a spherical volume having a diameter of about 6 cm. The configuration may be such that the electrodes of said at least two electroporation electrodes which are oppositely charged have at least 2 mm of spacing therebetween. In embodiments, the electrodes of said at least two electroporation electrodes which are oppositely charged may have at least 5 mm of spacing therebetween.

[0083] The inferior aspect of the operational space may be positioned at least 2 mm above the transverse pericardial sinus, and optionally no more than 20 mm above the transverse pericardial sinus.

[0084] Considering a spherical volume of operational space, the vertical axis of such a sphere may be positioned midway between the nominally vertical axes of the superior vena cava and the ascending aorta.

EXAMPLE 2

[0085] Apparatus for Use in Treating the Aortic Root Ganglionated Plexi

[0086] In an embodiment intended for treating the aortic root ganglionated plexi using at least two electroporation electrodes of opposite charge, the operational space including target tissue may be of maximum width dimension in the range of 4 to 8 cm, for example a spherical volume having a diameter of about 6 cm. The configuration may be such that the electrodes of said at least two electroporation electrodes which are oppositely charged have at least 2 mm of spacing therebetween. In embodiments, the electrodes of said at least two electroporation electrodes which are oppositely charged may have at least 10 mm of spacing therebetween.

[0087] Considering a spherical volume of operational space, the horizontal central axis of such a sphere can be aligned with the transverse sinus within a tolerance of +/10 mm. This places the operational space more inferior relative to the heart in comparison with the use in treating the aortocaval ganglionated plexi described in Example 1.

[0088] The vertical axis of the sphere may be positioned midway between the nominally vertical axes of the ascending aorta and the pulmonary trunk.

EXAMPLE 3

[0089] An apparatus suitable for carrying out an electroporation treatment (referring to FIG. 1) comprises first and second catheters having respectively first and second catheter tips (1; 3) of the curved loop type, with each curved loop tip (1, 3) bearing multiple electrodes (4; 6) respectively connectable by means of electrical conductors (7; 9) to positive (+) and negative () poles of a pulsed direct current power supply (8).

[0090] In use one pole () of the pulsed direct current power supply (8) may be connected to a catheter tip (1) positioned in the superior vena cava, and the other pole (+) of the pulsed direct current power supply (8) is connected to a catheter tip located in the aorta (3). The pulsed direct current electric field will be at its peak strength in between these catheter tips. The choice of polarity of electrode at each catheter tip in contact with the tissue does not matter provided always that a potential difference is established and at least one electrode in contact with tissue is of an opposite charge from at least one other electrode in contact with tissue, for example, of at least two electrodes one is positive and the other is negative.

EXAMPLE 4

[0091] An apparatus connectable by means of electrical conductors to positive (+) and negative () poles of a pulsed direct current power supply, as in Example 3, and suitable for carrying out an electroporation treatment (referring to FIG. 2) comprises a catheter assembly including first, second and third catheter tips (21; 22; 23) of the curved loop type, each curved loop tip (21, 22, 23) bearing multiple electrodes (24; 25; 26) and being respectively positioned in the right pulmonary artery, superior vena cava, and aorta.

[0092] In use, with the three catheter tips in place, the electrical field can be applied between any selected two catheter tips coupled such that a slightly different field focus exists with each alternate couple but throughout the ganglionated plexi are continuously electroporated. An electroporation voltage of 1000 Volts may be applied in a pulse of approximately 100 microseconds.

[0093] A possible sequence is illustrated in FIGS. 3a, 3b, and 3c, wherein a first catheter tip is coupled with a second catheter tip; then after a period of electroporation, the second catheter tip is coupled with the third catheter tip; then after a period of electroporation the first catheter tip is coupled with the third catheter tip. The catheter tip/electrode assembly is schematically represented as a filled circle in a natural vessel close to the ganglionated plexi (GP) and the sequence of coupled charges applied is indicated by +ve and ve for each stage. The electroporation period can be shorter than necessary to reach anticipated completion, and the said combinations may be cycled through in sequence with sufficient repetition to achieve completion.

EXAMPLE 5

[0094] The apparatus described for Example 4, may be used in a different method wherein two of the catheter tips are connected to the source to have the same polarity, whilst the third catheter tip is connected to the source to have the opposite polarity (as illustrated in FIG. 4. An electroporation voltage of 1000 Volts may be applied in a pulse of approximately 100 microseconds to provide higher field density focused on the ganglionated plexi.

EXAMPLE 6

[0095] The apparatus described for Example 4, may be used in a different method wherein two of the catheter tips are connected to the source to have the same polarity, whilst the third catheter tip is connected to the source to have the opposite polarity. In this embodiment as illustrated in FIG. 5, the level of voltage applied differs between different electrode couples. For example, an enhanced field may be created by applying 600 Volts between the first and third catheter tips, and 1000 Volts between the second and third catheter tips, whereby the voltage difference between the first and third catheter tips means that a current and field will also exist between them.

[0096] It will be understood that any of the three catheter tip illustrative embodiments disclosed here can be selected for any arrangement within any of the pulmonary arteries, superior vena cava, and aorta in order to maximise the electrical field imparted to the aortocaval ganglia, i.e. creating different three-dimensional field geometries. The differing fields could be applied simultaneously, or pulsed in sequence between different paired catheter tip electrodes. Equally, the aforesaid embodiments may also apply to electroporation of the aortic root ganglionated plexi located on the upper surface of the left ventricle boundary, adjacent to the right coronary artery. This aortic root ganglionated plexi can be treated by inserting the catheter tip electrodes into combinations of the aorta 64, pulmonary trunk 61, right coronary artery 62 and left coronary artery 63. In one illustrative procedure, a first catheter tip electrode may be positioned into the pulmonary trunk via the right atrium, right ventricle and just past the pulmonary valve. A second catheter tip electrode may be positioned into the proximal region of the right coronary artery, via the aorta, which permits creation of an electrical field between the first and second catheter tip electrodes to allow electroporation of the aortic root ganglionated plexi. Similarly, placing one catheter tip electrode in the aorta, just above the aortic valve, and a second catheter tip electrode 10-30 mm distally into the right coronary artery permits creation of another electrical field to allow electroporation of the aortic root ganglionated plexi. Alternatively placing catheter tip electrodes into the proximal regions of both left and right coronary arteries also allows electroporation of the aortic root ganglionated plexi (FIG. 6).

[0097] In still further embodiments, using three catheter tip electrodes as described for Examples 4 to 6 above may also be utilised to create additional electrode field shapes, all intersecting and ablating the aortic root ganglionated plexi.

[0098] In any of the embodiments, a voltage of 1000 Volts may be needed, with an operational range for the apparatus of 500-2000 Volts, being applied at a pulse duration of 100 microseconds, with an operational range of 1 microsecond to 1 millisecond. The resulting electroporation field strength will be in the region of 1000 Volts per centimetre depending on anatomical variations and positioning of the respective catheter tips. Multiple repeat pulses would be used, all pulses being monophasic. Such a region of field strength is anticipated to provide an operating zone that is primarily in the regime of reversible electroporation for myocardial tissue, but irreversible for ganglia structures in the fat pads.

EXAMPLE 7

[0099] A catheter tip and electrode assembly may be sheathed using a sheath having single or multiple apertures the size and shape of which may be the same or different.

[0100] Referring to FIG. 9 a circular aperture 70 in a sheath 71 is illustrated, and the sheath 71 would be moveable upon a catheter (not shown) axially and rotationally with respect to the longitudinal axis of the catheter so as to be fully or partially aligned with an electrode on the catheter tip to adjust electrical field emission.

[0101] Referring to FIG. 10 a rectangular aperture 72 in a sheath 73 is illustrated, and the sheath 73 would be moveable upon a catheter (not shown) axially and rotationally with respect to the longitudinal axis of the catheter by a user so as to be fully or partially aligned with an electrode on the catheter tip to adjust electrical field emission.

[0102] Referring to FIG. 12 a rectangular aperture 72 in a sheath 73 is illustrated, and the sheath is shown overlying a catheter tip and electrode assembly 75 such that the rectangular aperture or window is aligned with an electrode 76 on the catheter tip to allow electrical field emission.

[0103] The relative movement of the sheath with respect to the catheter can be achieved by a user manipulating a proximal handle of the catheter and/or a gripping portion of the overlying sheath.

[0104] The sheath may be a metal braided sheath as illustrated in FIG. 11 wherein a metal cellular pattern structure 77 serves as a Faraday cage concealed within a polymeric casing 78 of the sheath. The metal may be of any suitable conductive material such a conductive metal or alloy, for example copper, stainless steel or a nickel-titanium alloy (nitinol).

EXAMPLE 8

[0105] Various catheter tip and electrode assembly designs are useful for the purposes of the disclosed electroporation treatment. A suitable catheter has a throughbore through which electrical conductor wires can be passed to connect with the respective electrodes in the illustrated embodiments.

[0106] As illustrated in FIG. 13 a straight linear catheter tip 81 has spaced apart electrodes 83 attached to the catheter tip,

[0107] In FIG. 14 a bifurcated linear catheter tip 82 I shown which has spaced apart electrodes 84, 84 on the respective limbs of the bifurcated catheter tip 82.

[0108] A loop type, curvilinear catheter tip 85 bearing spaced electrodes 86 is illustrated in FIG. 15.

[0109] Each of the electrodes can be selectively controlled to operate together or individually in a sequence and at varying electrical field output.

EXAMPLE 9

[0110] Referring to FIGS. 16 and 17, an electrode configured to fit over a catheter tip may be of a tubular form 90 with an irrigation hole 91 to allow through flow of a fluid. The fluid may be introduced through a hollow catheter introduced to a throughbore 100 of electrode of the tubular form 90, and having a corresponding aperture to register with the irrigation hole 91.

EXAMPLE 10

[0111] FIG. 18 illustrates schematically a portion of a catheter tip and electrode assembly which is partially insulated, the catheter 105 bearing two spaced electrodes 106 each partially covered by an insulator 118, optionally the insulator 118 being a portion of an inflatable envelope or balloon; and FIG. 19 shows a cross-section [A-A] of the insulated electrode bearing potion of the catheter tip and electrode assembly

EXAMPLE 11

[0112] In a procedure requiring enhanced electroporation targeting epicardial ganglionated plexi embedded in fat pads on the outside surface of the heart, it is considered that in order to preferentially target the ganglia and mitigate the electroporation effect on the underlying myocardium, the effect of treatment temperature is to be taken account of. Effecting temperature control is achievable in the vicinity of the target ganglionated plexi by selective application of heat and/or cooling to tissue surfaces.

[0113] Referring to FIG. 7, an epicardial fat pad with ganglia is represented undergoing simultaneous temperature treatments such that by application of heat on the epicardial side, heating of the fat pad is achieved, and by application of cooling on the endocardial side, cooling of the myocardium is achieved. By selectively heating the fat pad, the ganglia become more susceptible to electroporation and thus can be targeted at a lower electrical field strength, which mitigates the risk of unintended damage to the myocardium. This risk of unintended damage is still further managed by introducing cooling of the myocardium tissue surface.

[0114] Cooling of the myocardium is achievable by introducing a chilled saline balloon, whereby the temperature of the myocardium may be cooled locally to about 5-30 C.

[0115] Heating of the fat pad is achievable by introducing a warm saline-containing balloon to overlie and contact the fat pad.

[0116] After the aforesaid temperature treatments are initiated, an electroporation apparatus including a bipolar catheter tip-electrode assembly may be introduced to contact epicardial tissue at spaced locations such that a (+) electrode of the catheter tip-electrode assembly is applied to the epicardial tissue or fat pad in the vicinity of the ganglia, and a () electrode is also applied to a different area of the epicardial tissue or fat pad in the vicinity of the ganglia (FIG. 8), the electrodes being connected to a D.C. source for effecting electroporation by means of an electrical field extending over the epicardial surface between the electrodes.

[0117] In alternative embodiments, an electrode, for example (+) electrode of the catheter tip-electrode assembly is introduced to contact epicardial tissue at a selected location of the epicardial tissue or fat pad in the vicinity of the ganglia, and another electrode of opposite polarity, in this example () electrode of the catheter tip-electrode assembly, is introduced to contact myocardial tissue in the vicinity of the ganglia, the electrodes being connected to a D.C. source for effecting electroporation by means of an electrical field extending through the myocardium between the electrodes.

[0118] An electroporation apparatus suitable for carrying out the procedure including temperature treatments comprises an elongate tubular catheter having a proximal end and a distal end, and internal fluid channels. The distal end of the catheter has spaced electrodes on a side surface, and a recess between the electrodes. The recess houses an inflatable balloon in communication with the internal fluid channels for receiving and venting a temperature control fluid, such as heated or cooled saline which may be circulated under pressure. Electrical conductor wires located upon or within the elongate tubular catheter are connectable to an external direct current supply with controller to adjust the voltage of the electrical supply.

[0119] In an alternative embodiment, the inflatable balloon for receiving a temperature controlled fluid is housed in a distal end face recess, instead of in a side surface of the elongate tubular catheter.

[0120] In still further alternative embodiments, a unipolar electroporation apparatus has a single distal end electrode connected to a direct current electrical supply. When used in a unipolar manner a single electrode would be used in conjunction with a back pad/dispersive electrode of opposite polarity on the patient (sometimes called an indifferent electrode).

[0121] Still further embodiments of the enhanced electroporation apparatus using differing combinations of electrodes, e.g. three electrodes as disclosed in Example 4 above are contemplated, and whilst examples are provided by way of illustration, it will be appreciated that these are indicative designs and that other designs with different overall shape and electrode arrangements are possible, so that these examples are non-limiting and attention is directed to the scope of the claims hereinafter appearing.