Modulation of intracellular calcium concentration using non-excitatory electrical signals applied to the tissue

• US 20030040777A1
• Filed: 04/03/2002
• Published: 02/27/2003
• Est. Priority Date: 01/08/1996
• Status: Active Grant

• Current Assignee: Bella Felzen, Itzik Shemer, Nissim Darvish, Ricardo Aviv, Walid Haddad, Yaakov Haham, Yuval Mika
• Original Assignee: Impulse Dynamics NV
• Inventors: Darvish, Nissim, Mika, Yuval, Haddad, Walid, Felzen, Bella, Aviv, Ricardo, Haham, Yaakov, Shemer, Itzik
• Granted Patent: US 8,825,152 B2
• Time in Patent Office: Days
• US Class Current: 607/9
• CPC Class Codes: A61N 1/3627 for treating a mechanical deficiency of the heart, e.g. congestive heart failure or cardiomyopathy
• CPC Class Codes: A61N 1/3628 using sub-threshold or non-excitatory signals
• CPC Class Codes: A61N 1/368 comprising more than one electrode co-operating with different heart regions A61N1/3622, A61N1/3627 take precedence

Abstract

According to a method and device for modulating intracellular calcium concentration in biological tissue, a stimulation probe is applied to the tissue, a non-excitatory stimulation pulse is generated, and the pulse is conveyed to the stimulation probe. In one embodiment concerning cardiac tissue, a stimulation probe is applied to a patient'"'"'s heart, a signal is received from at least one sensor responsive to the patient'"'"'s cardiac muscle activity, a non-excitatory stimulation pulse responsive to the signal is generated, and the pulse is conveyed to the stimulation probe.

Claims

1. A method of modulating intracellular calcium concentration in biological tissue, which comprises the steps of:

(a) applying a stimulation probe to biological tissue;

(b) generating a non-excitatory stimulation pulse; and

(c) conveying the pulse to the stimulation probe.

2. The method of claim 1, wherein the stimulation probe comprises one or more stimulation probes.

3. The method of claim 1, wherein the intracellular calcium concentration is increased.

4. The method of claim 1, wherein the intracellular calcium concentration is decreased.

5. A method of modulating intracellular calcium concentration in cardiac tissue, comprising:

(a) applying a stimulation probe comprising one or more stimulation electrodes to a subject'"'"'s heart;

(b) receiving a signal from at least one sensor responsive to the subject'"'"'s cardiac muscle activity;

(c) generating a non-excitatory stimulation pulse responsive to the signal; and

(d) conveying the pulse to at least one of the one or more electrodes.

6. The method of claim 5, wherein the intracellular calcium concentration is increased.

7. The method of claim 5, wherein the intracellular calcium concentration is decreased.

8. The method of claim 5, wherein receiving the signal comprises introducing a sensing electrode into the heart and receiving signals therefrom, and wherein generating the stimulation pulse comprises generating a pulse synchronized with electrical activity sensed by the sensing electrode.

9. The method of claim 5, wherein receiving the signal comprises applying an electrode to a body surface and receiving signals therefrom, and wherein generating the stimulation pulse comprises generating a pulse synchronized with an ECG signal.

10. The method of claim 5, wherein receiving the signal comprises receiving signals from at least one of the one or more stimulation electrodes.

11. The method of claim 5, wherein generating the stimulation pulse comprises generating a pulse having a predetermined delay relative to the signal.

12. The method of claim 5, wherein applying the stimulation probe comprises applying a probe comprising a plurality of stimulation electrodes, and wherein generating and conveying the pulse comprises generating a sequence of pulses and applying each pulse in the sequence to a different one of the plurality of stimulation electrodes.

13. The method of claim 5, wherein generating and conveying the stimulation pulse comprises generating and conveying stimulation pulses selectively, based on a characteristic of the signals received from the at least one sensor.

14. The method of claim 13, wherein generating and conveying the pulses comprises generating and applying pulses at a rate dependent on the heart rate, but not equal to the heart rate.

15. The method of claim 13, wherein generating and conveying the pulses comprises detecting a cardiac arrhythmia and adjusting the application of the pulses responsive thereto.

16. The method of claim 13, wherein generating and conveying the pulses comprises detecting a QT interval in the signals and generating pulses responsive thereto.

17. The method of claim 5, wherein generating the non-excitatory stimulation pulse comprises varying one or more parameters of the pulse, selected from the group consisting of the pulse voltage, current, duration, delay, and waveform frequency.

18. The method of claim 5, wherein the pulse comprises a baseline pulse and a waveform of substantially higher frequency than the baseline pulse superimposed thereon.

19. The method of claim 18, wherein the waveform comprises a square wave.

20. The method of claim 5, and comprising, after generating and conveying the non-excitatory stimulation pulse, generating and conveying another pulse of opposite polarity thereto.

21. The method of claim 5, wherein applying the non-excitatory stimulation pulse comprises varying the extent of a portion of the area of the heart segment to which the stimulation pulse is applied.

22. The method of claim 21, wherein varying the extent comprises selectively addressing a net of stimulation electrodes implanted in the heart.

23. The method of claim 5, wherein applying the stimulation probe comprises inserting the one or more stimulation electrodes into multiple chambers of the heart.

24. The method of claim 5 wherein implanting the stimulation probe comprises inserting at least one of the one or more stimulation electrodes into a blood vessel of the heart.

25. The method of claim 24, wherein inserting the at least one stimulation electrode comprises inserting the electrode into the coronary sinus.

26. The method of claim 5, wherein generating and conveying the pulse comprises generating and conveying pulses at selected times of day.

27. The method of claim 5, wherein generating and conveying the pulses comprises generating and conveying pulses which increase the subject'"'"'s cardiac output.

28. The method of claim 5 wherein generating and conveying the pulses comprises generating and conveying pulses which decrease the subject'"'"'s cardiac output.

29. The method of claim 5, wherein generating and conveying the pulses comprises generating and conveying pulses which increase the efficiency of contraction of the heart.

30. An apparatus for modulating intracellular calcium concentration in biological tissue, comprising:

a stimulation probe, and

an electrical control unit capable of generating a non-excitatory stimulation pulse and conveying said pulse to the stimulation probe to modulate intracellular calcium concentration.

31. The apparatus of claim 30, wherein the stimulation probe comprises one or more stimulation electrodes and the pulse is conveyed to one or more of said stimulation electrodes.

32. The apparatus of claim 30, wherein the intracellular calcium concentration is increased.

33. The apparatus of claim 30, wherein the intracellular calcium concentration is decreased.

34. An apparatus for modulating intracellular calcium concentration in cardiac tissue, comprising:

a stimulation probe comprising one or more stimulation electrodes,

at least one sensor capable of generating a signal responsive to cardiac activity, and

an electrical control unit capable of generating a non-excitatory stimulation pulse responsive to the signal and conveying said pulse to at least one or the one or more stimulation electrodes to modulate intracellular calcium concentration.

35. The apparatus of claim 34, wherein the intracellular calcium concentration is increased.

36. The apparatus of claim 34, wherein the intracellular calcium concentration is decreased.

37. The apparatus of claim 34, which also comprises a sensing electrode to be introduced into the heart to sense signals and the stimulation pulse is synchronized with electrical activity sensed by the sensing electrode.

38. The apparatus of claim 34, wherein the stimulation pulse is synchronized with an ECG signal from an electrode applied to a body surface.

39. The apparatus of claim 34, wherein signals are received from at least one of the one or more stimulation electrodes.

40. The apparatus of claim 34, wherein the stimulation pulse generated has a predetermined delay relative to the signal.

41. The apparatus of claim 34, wherein the stimulation probe comprises a plurality of stimulation electrodes, and wherein the electrical control unit generates a sequence of pulses and applies each pulse in the sequence to a different one of the plurality of stimulation electrodes.

42. The apparatus of claim 34, wherein the electrical control unit generates and conveys stimulation pulses selectively, based on a characteristic of the signals received from the at least one sensor.

43. The apparatus of claim 42, wherein the electrical control unit generates and applies pulses at a rate dependent on the heart rate, but not equal to the heart rate.

44. The apparatus of claim 42, wherein the electrical control unit detects a cardiac arrhythmia and adjusts the application of the pulses responsive thereto.

45. The apparatus of claim 42, wherein the electrical control unit detects a QT interval in the signals and generates pulses responsive thereto.

46. The apparatus of claim 34, wherein in generating the non-excitatory stimulation pulse the electrical control unit varies one or more parameters of the pulse selected from the group consisting of the pulse voltage, current, duration, delay, and waveform frequency.

47. The apparatus of claim 34, wherein the pulse comprises a baseline pulse and a waveform of substantially higher frequency than the baseline pulse superimposed thereon.

48. The apparatus of claim 47, wherein the waveform comprises a square wave.

49. The apparatus of claim 34, wherein after generating and conveying the non-excitatory stimulation pulse, the electrical control unit generates and conveys another pulse of opposite polarity thereto.

50. The apparatus of claim 34, wherein the electrical control unit varies the extent of a portion of the area of the heart segment to which the non-excitatory stimulation pulse is applied.

51. The apparatus of claim 50, wherein varying the extent comprises selectively addressing a net of stimulation electrodes implanted in the heart.

52. The apparatus of claim 34, wherein the one or more stimulation electrodes as inserted into multiple chambers of the heart.

53. The apparatus of claim 34, wherein at least one of the one or more stimulation electrodes are inserted into a blood vessel of the heart.

54. The apparatus of claim 34, wherein at least one stimulation electrode is inserted into the coronary sinus.

55. The apparatus of claim 34, wherein the electrical control unit generates and conveys pulses at selected times of day.

56. The apparatus of claim 34, wherein the electrical control unit generates and conveys pulses which increase the subject'"'"'s cardiac output.

57. The apparatus of claim 34, wherein the electrical control unit generates and conveys pulses which decrease the subject'"'"'s cardiac output.

58. The apparatus of claim 34, wherein the electrical control unit generates and conveys pulses which increase the efficiency of contraction of the heart.