Methods and apparatus for bilateral renal neuromodulation

• US 20060265014A1
• Filed: 03/06/2006
• Published: 11/23/2006
• Est. Priority Date: 04/08/2002
• Status: Active Grant

• Current Assignee: Medtronic Ardian Luxembourg SARL (Medtronic Plc)
• Original Assignee: Ardian, Inc. (Medtronic Plc)
• Inventors: Levin, Howard R., Demarais, Denise, Gelfand, Mark, Gifford, Hanson III, Sutton, Douglas, Deem, Mark
• Granted Patent: US 8,150,519 B2
• Time in Patent Office: Days
• US Class Current: 607/2
• CPC Class Codes: A61B 18/12 by passing a current through the tissue to be heated, e.g. high-frequency current
• CPC Class Codes: A61B 18/14 Probes or electrodes therefor
• CPC Class Codes: A61B 18/1492 having a flexible, catheter-like structure, e.g. for heart ablation A61B18/1477 takes precedence
• CPC Class Codes: A61B 2018/00267 having a basket shaped structure
• CPC Class Codes: A61B 2018/00351 Heart
• CPC Class Codes: A61B 2018/00404 Blood vessels other than those in or around the heart
• CPC Class Codes: A61B 2018/00434 Neural system
• CPC Class Codes: A61B 2018/00511 Kidney
• CPC Class Codes: A61B 2018/00577 Ablation
• CPC Class Codes: A61B 2018/00613 Irreversible electroporation
• CPC Class Codes: A61M 2210/1082 Kidney
• CPC Class Codes: A61M 5/1408 in parallel, e.g. manifolds, sequencing valves access sites A61M39/02; tube connectors A61M39/10
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61N 1/0412 Specially adapted for transcutaneous electroporation, e.g. including drug reservoirs
• CPC Class Codes: A61N 1/05 for implantation or insertion into the body, e.g. heart electrode A61N1/06 takes precedence
• CPC Class Codes: A61N 1/0551 Spinal or peripheral nerve electrodes
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: A61N 1/36007 of urogenital or gastrointestinal organs, e.g. for incontinence control
• CPC Class Codes: A61N 1/36017 with leads or electrodes penetrating the skin
• CPC Class Codes: A61N 7/00 Ultrasound therapy lithotripsy A61B17/22, A61B17/225; massage using supersonic vibration A61H23/00 ; using ultrasound for introducing media into the body A61M37/0092

Abstract

Methods and apparatus are provided for bilateral renal neuromodulation, e.g., via a pulsed electric field, via a stimulation electric field, via localized drug delivery, via high frequency ultrasound, via thermal techniques, etc. Such neuromodulation may effectuate irreversible electroporation or electrofusion, necrosis and/or inducement of apoptosis, alteration of gene expression, action potential attenuation or blockade, changes in cytokine up-regulation and other conditions in target neural fibers. In some embodiments, neuromodulation is applied to neural fibers that contribute to renal function. In some embodiments, such neuromodulation is performed in a bilateral fashion. Bilateral renal neuromodulation may provide enhanced therapeutic effect in some patients as compared to renal neuromodulation performed unilaterally, i.e., as compared to renal neuromodulation performed on neural tissue innervating a single kidney.

Claims

1. A method for bilateral renal neuromodulation, the method comprising:

modulating at least a first neural fiber that contributes to renal function of a first kidney of a patient; and

modulating at least a second neural fiber that contributes to renal function of a second kidney of the patient, thereby achieving bilateral renal neuromodulation.

2. The method of claim 1, wherein modulating a first neural fiber that contributes to renal function of a first kidney of a patient further comprises modulating a right neural fiber that contributes to right renal function, and

wherein modulating a second neural fiber that contributes to renal function of a second kidney of a patient further comprises modulating a left neural fiber that contributes to left renal function.

3. The method of claim 1, wherein modulating a first neural fiber that contributes to renal function of a first kidney of a patient further comprises modulating a left neural fiber that contributes to left renal function, and

wherein modulating a second neural fiber that contributes to renal function of a second kidney of a patient further comprises modulating a right neural fiber that contributes to right renal function.

4. The method of claim 1, wherein modulating the first neural fiber and modulating the second neural fiber further comprises concurrently modulating the first and second neural fibers.

5. The method of claim 1, wherein modulating the first neural fiber and modulating the second neural fiber further comprises sequentially modulating the first and second neural fibers.

6. The method of claim 1, wherein modulating the first neural fiber and modulating the second neural fiber further comprises modulating the first neural fiber and modulating the second neural fiber via apparatus positioned within renal vasculature of the patient.

7. The method of claim 1, wherein modulating the first neural fiber and modulating the second neural fiber further comprises modulating the first neural fiber and modulating the second neural fiber via apparatus positioned external to renal vasculature of the patient.

8. The method of claim 1, wherein modulating the first neural fiber and modulating the second neural fiber further comprises modulating the first neural fiber and modulating the second neural fiber via apparatus positioned in proximity to renal vasculature of the patient.

9. The method of claim 1, wherein modulating the first neural fiber and modulating the second neural fiber further comprises modulating the first neural fiber and modulating the second neural fiber via apparatus positioned within renal vasculature of the patient and having a neuromodulatory element passed extravascularly.

10. The method of claim 1, wherein modulating the first neural fiber and modulating the second neural fiber further comprises modulating the first and second neural fibers via electric fields.

11. The method of claim 10, wherein modulating the first and second neural fibers via electric fields further comprises exposing the first and second neural fibers to pulsed electric fields.

12. The method of claim 10, wherein modulating the first and second neural fibers via electric fields further comprises exposing the first and second neural fibers to stimulation electric fields.

13. The method of claim 1, wherein modulating the first neural fiber and modulating the second neural fiber further comprises delivering a neuromodulatory agent to the first and second neural fibers.

14. The method of claim 1, wherein modulating the first neural fiber and modulating the second neural fiber further comprises at least partially denervating the first and second kidneys.

15. The method of claim 1, wherein modulating the first neural fiber and modulating the second neural fiber further comprises inducing an effect in the first and second neural fibers chosen from the group consisting of irreversible electroporation, electrofusion, necrosis, apoptosis, gene expression alteration, action potential attenuation, action potential blockade, cytokine up-regulation alteration, and combinations thereof.

16. The method of claim 1, wherein modulating the first neural fiber and modulating the second neural fiber further comprises continuously modulating the first and second neural fibers.

17. The method of claim 1, wherein modulating the first neural fiber and modulating the second neural fiber further comprises intermittently modulating the first and second neural fibers.

18. Apparatus for bilateral renal neuromodulation, the apparatus comprising:

a first field applicator configured to be positioned proximate to at least a first neural fiber that contributes to right renal function;

a second field applicator configured to be positioned proximate to at least a second neural fiber that contributes to left renal function; and

a field generator coupled to the first and second field applicators,

wherein the field generator is configured to provide a first signal to the first field applicator and a second signal to the second field applicator.

19. The apparatus of claim 18, wherein the first field applicator and the second field applicator comprise intravascular field applicators configured for placement within renal vasculature of the patient.

20. The apparatus of claim 18, wherein the first field applicator and the second field applicator comprise extravascular field applicators configured for placement in external proximity to renal vasculature of the patient.

21. The apparatus of claim 18, wherein the first field applicator and the second field applicator comprise intra-to-extravascular field applicators configured for extravascular placement via an intra-to-extravascular approach.

22. The apparatus of claim 18, wherein the first field applicator and the second field applicator comprise field applicators configured for a combination of placement within renal vasculature of the patient, placement in external proximity to renal vasculature of the patient or extravascular placement via an intra-to-extravascular approach.

23. The apparatus of claim 18, wherein the field generator further comprises a pulsed electric field generator.

24. The apparatus of claim 18, wherein the first field applicator and the second field applicator comprise electrodes configured for placement in proximity to the first and second neural fibers, and wherein the electrodes are coupled to the field generator for delivery of electric fields to the first and second neural fibers.

25. The apparatus of claim 24, wherein the first field applicator and the second field applicator comprise a first bipolar electrode pair and a second bipolar electrode pair.

26. The apparatus of claim 24, wherein the first field applicator and the second field applicator comprise a first monopolar electrode and a second monopolar electrode, the apparatus further comprising at least one ground pad configured for external attachment to the patient.

27. The apparatus of claim 24, wherein the first field applicator comprises a bipolar electrode pair and the second field applicator comprises a monopolar electrode, the apparatus further comprising a ground pad configured for external attachment to the patient.

28. The apparatus of claim 24, wherein the first field applicator comprises a monopolar electrode and the second field applicator comprises a bipolar electrode pair, the apparatus further comprising a ground pad configured for external attachment to the patient.

29. The apparatus of claim 18, wherein the field generator is configured to concurrently provide a first signal to the first field applicator and a second signal to the second field applicator.

30. The apparatus of claim 18, wherein the field generator is configured to sequentially provide a first signal to the first field applicator and a second signal to the second field applicator.

31. The apparatus of claim 18, wherein the field generator is configured to continuously provide a first signal to the first field applicator and a second signal to the second field applicator.

32. The apparatus of claim 18, wherein the field generator is configured to intermittently provide a first signal to the first field applicator and a second signal to the second field applicator.

33. A method for bilateral renal neuromodulation, the method comprising:

modulating neural fibers that contribute to right renal function of a patient; and

modulating neural fibers that contribute to left renal function of the patient.

34. The method of claim 33, wherein modulating neural fibers that contribute to right and left renal function further comprises denervating the right and left kidneys of the patient.

35. The method of claim 33, wherein modulating neural fibers that contribute to right and left renal function further comprises inducing an effect in the neural fibers chosen from the group consisting of irreversible electroporation, electrofusion, necrosis, apoptosis, gene expression alteration, action potential attenuation, action potential blockade, cytokine up-regulation alteration, and combinations thereof.

36. The method of claim 33, wherein modulating neural fibers that contribute to right and left renal function further comprises:

positioning modulating apparatus within right and left renal vasculature of the patient, and

modulating the neural fibers with the modulating apparatus.

37. The method of claim 33, wherein modulating neural fibers that contribute to right and left renal function further comprises:

positioning modulating apparatus in a vicinity of right and left renal vasculature of the patient, and

modulating the neural fibers with the modulating apparatus.

38. The method of claim 37, wherein positioning modulating apparatus in the vicinity of the right and left renal vasculature of the patient further comprises positioning the modulating apparatus within the patient external to the renal vasculature.

39. The method of claim 38, wherein positioning the modulating apparatus within the patient external to the renal vasculature further comprises positioning the modulating apparatus within the patient external to the renal vasculature via an intra-to-extravascular approach.

40. The method of claim 33, wherein modulating neural fibers that contribute to right and left renal function further comprises applying an electric field to the right and left neural fibers.

41. The method of claim 40, wherein applying an electric field to the right and left neural fibers further comprises applying a pulsed electric field to the right and left neural fibers.

42. The method of claim 40, wherein applying an electric field to the right and left neural fibers further comprises applying a stimulation electric field to the right and left neural fibers.

43. The method of claim 33, wherein modulating neural fibers that contribute to right and left renal function further comprises delivering a neuromodulatory agent to the right and left neural fibers.

44. The method of claim 33, wherein modulating neural fibers that contribute to right and left renal function further comprises concurrently modulating neural fibers that contribute to right and left renal function.

45. The method of claim 33, wherein modulating neural fibers that contribute to right and left renal function further comprises sequentially modulating neural fibers that contribute to right and left renal function.

46. The method of claim 33, wherein modulating neural fibers that contribute to right and left renal function further comprises continuously modulating neural fibers that contribute to right and left renal function.

47. The method of claim 33, wherein modulating neural fibers that contribute to right and left renal function further comprises intermittently modulating neural fibers that contribute to right and left renal function.

48. Apparatus for bilateral renal neuromodulation, the apparatus comprising:

a first drug delivery element configured to be positioned proximate to a first neural fiber that contributes to right renal function;

a second drug delivery element configured to be positioned proximate to a second neural fiber that contributes to left renal function; and

a drug reservoir comprising a neuromodulatory agent, the drug reservoir coupled to the first and second drug delivery elements,

wherein the drug reservoir is configured to deliver the neuromodulatory agent to the first drug delivery element and the second drug delivery element.

49. The apparatus of claim 48, wherein the drug reservoir comprises an implantable drug pump.

50. The apparatus of claim 48, wherein the drug reservoir comprises an external drug reservoir.

51. The apparatus of claim 48, wherein the drug reservoir is configured to concurrently deliver the neuromodulatory agent to the first drug delivery element and the second drug delivery element.

52. The apparatus of claim 48, wherein the drug reservoir is configured to sequentially deliver the neuromodulatory agent to the first drug delivery element and the second drug delivery element.

53. The apparatus of claim 48, wherein the drug reservoir is configured to continuously deliver the neuromodulatory agent to the first drug delivery element and the second drug delivery element.

54. The apparatus of claim 48, wherein the drug reservoir is configured to intermittently deliver the neuromodulatory agent to the first drug delivery element and the second drug delivery element.