Protein activity modification

• US 9,931,503 B2
• Filed: 12/09/2005
• Issued: 04/03/2018
• Est. Priority Date: 03/10/2003
• Status: Active Grant

• Current Assignee: Impulse Dynamics NV
• Original Assignee: Impulse Dynamics NV
• Inventors: Rousso, Benny, Mika, Yuval, Sabbah, Hani N., Ben-Haim, Shlomo
• Primary Examiner(s): Heller, Tammie K
• Application Number:
  US11/792,811
• Publication Number:
  US 20090292324A1
• Time in Patent Office: 4,498 Days
• CPC Class Codes: A61N 1/205 for promoting a biological process
• CPC Class Codes: A61N 1/32 alternating or intermittent currents applying electric fields by inductive or capacitive coupling A61N1/40; microwave apparatus A61N5/02
• CPC Class Codes: A61N 1/326 for promoting growth of cells, e.g. bone cells
• CPC Class Codes: C12N 13/00 Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves

Abstract

A method of modifying cardiac tissue behavior, comprising applying a therapeutically effective electric field having an effect of modifying protein activation levels of at least one protein, and repeatedly applying the field at time intervals timed to increase the activation levels of the at least one protein beyond an activation level achieved by natural and/or paced excitation of the muscle without the application, to an extent about at least as high as a decay of the activation between applications of the field.

Claims

1. A method of modifying cardiac tissue behavior of a patient'"'"'s heart, comprising:

applying a therapeutically effective electric field to at least a portion of said heart, said field when applied to the heart having an effect of modifying protein activation levels of at least one protein, thereby modifying a protein activation level of at least one protein; and

repeatedly applying said field at time intervals defining delays between successive applications, during which said delays said modified protein activation level decays, and said applying timed to increase said protein activation level of said at least one protein (i) beyond an amount achieved by a natural and/or paced excitation of said heart absent said applying and (ii) by an amount at least as high as a decay of said protein activation level between applications of said field,

wherein said applying comprises modifying a protein activation level of protein already synthesized before said applying.

2. The method according to claim 1, wherein applying said field comprises repeatedly applying over a group of heart beats at time intervals timed according to a cardiac cycle of said patient.

3. The method according to claim 1, wherein a duration of an application is within a duration of a single cardiac cycle.

4. The method according to claim 1, wherein a duration of an application repeated for a plurality of cardiac cycles of said patient, and each application extends within the duration of each of a plurality of cardiac cycles of said patient.

5. The method according to claim 1, wherein said applying is delivered over a plurality of cardiac cycles of said patient.

6. The method according to claim 1, wherein said applying having an interval between applications which is spread over a plurality of cardiac cycles of said patient.

7. The method according to claim 1, wherein said modifying protein activation levels of at least one protein comprises phosphorylation of said at least one protein.

8. The method according to claim 1, wherein said modifying protein activation levels of at least one protein comprises dephosphorylation of said at least one protein.

9. The method according to claim 1, wherein said time intervals are timed so that an expected decay of said protein activation level between applications is the same as an expected increase in said level caused by said applying.

10. The method according to claim 1, wherein said time intervals are timed so that an expected decay of modifying protein activation levels between applications is smaller than an expected increase in said level caused by said applying.

11. The method according to claim 1, wherein said applying of said field comprises applying a therapeutically effective electric field that causes a 10% increase in a contractility of said heart of said patient over a period of 5 minutes from an initial application.

12. The method according to claim 1, wherein said field reduces heart contractility.

13. The method according to claim 1, wherein said field increases heart contractility.

14. The method according to claim 1, wherein said time intervals are timed to an absolute refractory period of a cardiac cycle of said patient.

15. The method according to claim 14, wherein applying said field is provided at least during 60% of a cardiac cycle of said patient.

16. The method according to claim 14, wherein applying said field is provided at least during 80% of a cardiac cycle of said patient.

17. The method according to claim 14, comprising applying said field during 60% of a cardiac cycle of said patient at most.

18. The method according to claim 14, comprising applying said field during 80% of a cardiac cycle of said patient at most.

19. The method according to claim 1, wherein said applying comprises applying a therapeutically effective electric field having a desired effect of above 10% increase in said modifying protein activation levels.

20. The method according to claim 19, wherein said time intervals are timed to be synchronized to an activity of a whole heart of said patient.

21. The method according to claim 19, wherein said time intervals are timed to be synchronized to an activity of a local heart region of said patient.

22. The method according to claim 21, wherein said local heart region is ischemic.

23. The method according to claim 21, wherein said local heart region is non-ischemic.

24. The method according to claim 21, further comprising applying a second therapeutically effective electric field to a second local heart region.

25. The method according to claim 24, wherein applying said second therapeutically effective electric field increases a contractility of said second local heart region.

26. The method according to claim 1, wherein said applying comprises a plurality of applications of said therapeutically effective electric field.

27. The method according to claim 26, wherein said plurality of applications comprises 10 applications.

28. The method according to claim 26, wherein said plurality of applications comprises 20 applications.

29. The method according to claim 26, wherein said plurality of applications comprises 30 applications.

30. The method according to claim 1, wherein said repeatedly applying comprises applying at least two of said therapeutically effective electric fields and said time intervals comprise delivering less often than once in 5 minutes.

31. The method according to claim 1, wherein said repeatedly applying comprises applying at least two of said therapeutically effective electric field and said time intervals comprise delivering less often than once in 10 minutes.

32. The method according to claim 1, wherein said repeatedly applying comprises applying at least two of said therapeutically effective electric field and said time intervals comprise delivering less often than once in 30 minutes.

33. The method according to claim 1, wherein said repeatedly applying comprises applying at least two of said therapeutically effective electric field and time intervals comprise delivering less often than once in 1 hour.

34. The method according to claim 1, wherein said repeatedly applying comprises applying at least two of said therapeutically effective electric field and said time intervals comprise delivering less often than once a day.

35. The method according to claim 1, wherein said repeatedly applying comprises applying at least two of said therapeutically effective electric field and said time intervals comprise delivering less often than once a week.

36. The method of claim 1, wherein said applying comprises determining a refractory period of said heart and synchronizing said applying and said delays so that said applying is during said determined refractory period.

37. The method of claim 1, wherein during which said delays said modified protein activation level has an expected decay, and wherein said (ii) is by an amount at least as high as said expected decay.

38. The method of claim 1, wherein said repeatedly applying comprises repeating said applying at least 30 times, with a delay of at least 1 minute between each repeated application.

39. The method of claim 1, wherein said repeatedly applying comprises applying in spurts of less than 100 seconds with delays between spurts.

40. An apparatus for modifying cardiac tissue behavior of a patient'"'"'s heart, comprising:

at least one electrode adapted to apply an electric field to at least a portion of said heart, said field when applied to the heart having an effect of modifying protein activation levels of at least one protein; and

circuitry having instructions to repeatedly electrify said at least one electrode at time intervals defining delays between successive applications, during which said delays said modified protein activation level decays, and said electrifying timed to increase said protein activation levels of said at least one protein (i) beyond an amount achieved by a natural and/or paced excitation of said heart absent said application and (ii) by an amount at least as high as a decay of said protein activation level between applications of said field wherein said electrifying comprises increasing a protein activation level of protein already synthesized before said applying.

41. The apparatus according to claim 40, wherein said circuitry further comprises instructions to electrify said at least one electrode such that said electric field is non-excitatory in at least part of said applications of said field.

42. The apparatus according to claim 40, being programmed to use a minimum amount of power sufficient to affect said protein activation levels.

43. The apparatus of claim 40, wherein said circuitry is configured to determine a refractory period of said heart and synchronize said electrifying and said delays so that said electrifying is during said determined refractory period.