Stimulus regimens for cardiovascular reflex control

• US 20040254616A1
• Filed: 04/05/2004
• Published: 12/16/2004
• Est. Priority Date: 09/27/2000
• Status: Active Grant

• Current Assignee: CVRx, Inc.
• Original Assignee: CVRx, Inc.
• Inventors: Serdar, David J., Persson, Bruce J., Rossing, Martin A., Kieval, Robert S.
• Granted Patent: US 7,623,926 B2
• Time in Patent Office: Days
• US Class Current: 607/42
• CPC Class Codes: A61N 1/0551 Spinal or peripheral nerve electrodes
• CPC Class Codes: A61N 1/0558 Anchoring or fixation means therefor
• CPC Class Codes: A61N 1/36007 of urogenital or gastrointestinal organs, e.g. for incontinence control
• CPC Class Codes: A61N 1/36114 Cardiac control, e.g. by vagal stimulation stimulating the heart A61N1/362
• CPC Class Codes: A61N 1/36117 for treating hypertension
• 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 1/36514 controlled by a physiological quantity other than heart potential, e.g. blood pressure controlled by two or more physical parameters A61N1/36585

Abstract

Baroreflex activation is achieved by providing suitable control signals to a baroreflex activation device. A method comprises establishing a therapy interval (possibly on the order of minutes to hours, or possibly of indefinite duration), within the therapy interval, establishing a plurality of dose intervals, and generating an electrical output signal. The electrical output signal has a time dependence such that the average electrical power applied to the baroreflex activation device differs between first and second portions of at least some dose intervals. Another method comprises establishing a series of therapy interval portions, during at least some therapy intervals, establishing a plurality of burst intervals (perhaps having durations commensurate with an interval between heartbeats), and generating an electrical output signal. The electrical output signal has a time dependence such that the average electrical power applied to the baroreflex activation device differs between first and second portions of the therapy intervals and also differs between first and second portions of at least some burst intervals.

Claims

1. A method of generating an electrical control signal for application to a baroreflex activation device, the method comprising:

establishing a therapy interval;

within the therapy interval, establishing a plurality of dose intervals; and

generating an electrical output signal characterized in that electrical power applied to the baroreflex activation device has a time dependence wherein at least some dose intervals have a first portion characterized by an average electrical power, referred to as the first dose portion average power, and a second portion characterized by an average electrical power, referred to as the second dose portion average power, the first dose portion average power being different from the second dose portion average power.

2. The method of claim 1, and further comprising positioning the baroreflex activation device proximate one or more baroreceptors.

3. The method of claim 1, and further comprising positioning the baroreflex activation device proximate one or more nerve fibers that carry signals from a baroreceptor to the brain.

4. The method of claim 1 wherein generating the electrical output signal comprises generating electrical pulses having one or more pulse characteristics chosen to provide said time dependence of electrical power applied to the baroreflex activation device.

5. The method of claim 4 wherein said pulse characteristics include one or more of pulse amplitude, pulse width, pulse frequency, pulse separation, pulse waveform, pulse polarity, and pulse phase.

6. The method of claim 1 wherein the difference between the first dose portion average power and the second dose portion average power is achieved by generating pulses in the first and second portions of the dose interval that differ in at least one of burst frequency, amplitude, and pulse width.

7. The method of claim 1 wherein the therapy interval is on the order of minutes to hours.

8. The method of claim 1 wherein the therapy interval is of an indefinite duration.

9. The method of claim 1 wherein the dose intervals are triggered by a signal having a correlation with a physiologic response that is characterized by a longer time interval than a cardiac cycle.

10. The method of claim 9 wherein the physiologic response is respiration.

11. The method of claim 9 wherein the physiologic response is one or more of inspiration and expiration.

12. The method of claim 1 wherein the second dose portion average power is zero for at least some dose intervals.

13. The method of claim 1 wherein the first portion of at least one dose interval is characterized by a variation in first dose portion average power, wherein the first dose portion average power near the center of the first portion of the dose interval is greater than the first dose portion average power near the beginning and end of the first portion of the dose interval.

14. The method of claim 13 wherein the variation in first dose portion average power is characterized by a generally linear region of positive slope near the beginning of the first portion of the dose interval, a generally flat region near the center of the first portion of the dose interval, and a generally linear region of negative slope near the end of the first portion of the dose interval.

15. The method of claim 1 wherein the therapy interval is characterized by a variation in average power over a plurality of dose intervals, wherein the average power rises during dose intervals near the beginning of the therapy interval.

16. The method of claim 1 wherein the therapy interval has a time dependence wherein a first portion is characterized by an average electrical power, referred to as the first therapy portion average power, over a first plurality of dose intervals, and a second portion characterized by an average electrical power, referred to as the second therapy portion average power, over a second plurality of dose intervals, the first therapy portion average power being different from the second therapy portion average power.

17. The method of claim 16 wherein the second therapy portion average power is zero.

18. The method of claim 16 wherein the therapy interval is characterized by a variation in average power over a plurality of dose intervals.

19. The method of claim 18 wherein the therapy interval'"'"'s variation in average power is characterized by a generally linear region of positive slope over a first set of dose intervals near the beginning of the therapy interval, followed by a generally flat region over a second set of dose intervals and a generally linear region of negative slope over a third set of dose intervals.

20. The method of claim 16 wherein the average power during dose intervals near the center of the first portion of the therapy interval is greater than the average power during dose intervals near the beginning and end of the first portion of the therapy interval.

21. The method of claim 16, and further comprising establishing additional therapy intervals, each of which has a first portion characterized by a first therapy portion average power over a first plurality of dose intervals and a second portion characterized by a second therapy portion average power over a second plurality of dose intervals, the first therapy portion average power being different from the second therapy portion average power.

22. The method of claim 21 wherein at least some therapy intervals are longer than other therapy intervals.

23. The method of claim 21 wherein each therapy interval is on the order of minutes to hours.

24. The method of claim 21 wherein for at least some therapy intervals, the first portion is longer than the second portion.

25. The method of claim 21 wherein the average electrical power applied to the baroreflex activation device has a time dependence characterized by ascending ramps near the respective beginnings of the first portions of the therapy intervals and descending ramps near the respective ends of the first portions of the therapy intervals.

26. The method of claim 21 wherein at least two successive therapy intervals are of equal length and have respective first portions that are of equal length.

27. The method of claim 1 wherein a first set of the electrical pulses is applied to a first of a plurality of baroreflex activation devices and a second set of the electrical pulses is applied to a second of the plurality of baroreflex activation devices.

28. The method of claim 27, and further comprising establishing additional therapy intervals, wherein the first and second sets of electrical pulses are interleaved at the individual therapy interval level.

29. The method of claim 27 wherein the first and second sets of electrical pulses are interleaved at the dose interval level.

30. The method of claim 27 wherein the first and second sets of electrical pulses are interleaved at the individual pulse level.

77. A baroreflex activation system comprising:

a baroreflex activation device;

a control system configured to

establish a therapy interval,

establish, within the therapy interval, a plurality of dose intervals, and

generate an electrical output signal for application to the baroreflex activation device, the electrical output signal being characterized in that electrical power applied to the baroreflex activation device has a time dependence as recited in claim 1;

and

an interconnection mechanism that applies the electrical signal to the baroreflex activation device.

31. A method of generating an electrical control signal for application to a baroreflex activation device, the method comprising:

establishing a series of therapy intervals;

during at least some therapy intervals, establishing a plurality of burst intervals; and

generating an electrical output signal characterized in that electrical power applied to the baroreflex activation device has a time dependence wherein

at least some therapy intervals have a first portion characterized by an average electrical power, referred to as the first therapy portion average power, and a second portion characterized by an average electrical power, referred to as the second therapy portion average power, the first therapy portion average electrical power being different from the second therapy portion average electrical power, and

at least some burst intervals have a first portion characterized by an average electrical power, referred to as the first burst portion average power, and a second portion characterized by an average electrical power, referred to as the second burst portion average power, the first burst portion average power being different from the second burst portion average power.

32. The method of claim 31, and further comprising positioning the baroreflex activation device proximate one or more baroreceptors.

33. The method of claim 31, and further comprising positioning the baroreflex activation device proximate one or more nerve fibers that carry signals from a baroreceptor to the brain.

34. The method of claim 31 wherein generating the electrical output signal comprises generating electrical pulses having one or more pulse characteristics chosen to provide said time dependence of electrical power applied to the baroreflex activation device.

35. The method of claim 34 wherein said pulse characteristics include one or more of pulse amplitude, pulse width, pulse frequency, pulse separation, pulse waveform, pulse polarity, and pulse phase.

36. The method of claim 31 wherein the therapy intervals are on the order of minutes to hours.

37. The method of claim 31 wherein the burst intervals are commensurate with an interval between heartbeats.

40. The method of claim 31 wherein the average electrical power applied to the baroreflex activation device has a time dependence characterized by ascending ramps near the respective beginnings of the first portions of the therapy intervals and descending ramps near the respective ends of the first portions of the therapy intervals.

41. The method of claim 31 wherein at least two successive therapy intervals are of equal length and have respective first portions that are of equal length.

42. The method of claim 31 wherein the second burst portion average power is zero.

43. The method of claim 31 wherein the difference between the first therapy portion average power and the second therapy portion average power is achieved by generating pulses in the first and second portions of the therapy interval that differ in at least one of burst frequency, amplitude, and pulse width.

44. The method of claim 31 wherein the difference between the first burst portion average power and the second burst portion average power is achieved by generating pulses in the first and second portions of the burst interval that differ in at least one of burst frequency, amplitude, and pulse width.

45. The method of claim 31 wherein the first burst portion includes pulses at a first burst frequency and the second burst portion includes pulses at a second burst frequency that is lower than the first burst frequency.

46. The method of claim 31 wherein the first burst portion includes pulses having a first amplitude and the second burst portion includes pulses having a second amplitude that is lower than the first amplitude.

47. The method of claim 31 wherein the first burst portion includes pulses having a first average pulse width and the second burst portion includes pulses having a second average pulse width that is lower than the first average pulse width.

48. The method of claim 31 wherein the first portion of the burst interval is characterized by a variation in average power over a plurality of pulses.

49. The method of claim 31 wherein a first set of the electrical pulses is applied to a first of a plurality of baroreflex activation devices and a second set of the electrical pulses is applied to a second of the plurality of baroreflex activation devices.

50. The method of claim 49 wherein the first and second sets of electrical pulses are interleaved at the individual therapy interval level.

51. The method of claim 49 wherein the first and second sets of electrical pulses are interleaved at the dose interval level.

52. The method of claim 49 wherein the first and second sets of electrical pulses are interleaved at the burst interval level.

53. The method of claim 49 wherein the first and second sets of electrical pulses are interleaved at the individual pulse level.

78. A baroreflex activation system comprising:

a baroreflex activation device;

a control system configured to

establish a series of therapy intervals,

establish, during at least some therapy intervals, a plurality of burst intervals, and

generate an electrical output signal for application to the baroreflex activation device, the electrical signal being characterized in that electrical power applied to the baroreflex activation device has a time dependence as recited in claim 31;

and

an interconnection mechanism that applies the electrical output signal to the baroreflex activation device.

54. A method of generating an electrical control signal for application to a baroreflex activation device, the method comprising:

establishing a therapy interval;

within the therapy interval, establishing a plurality of dose intervals;

within each dose interval, establishing a plurality of burst intervals; and

generating an electrical output signal characterized in that electrical power applied to the baroreflex activation device has a time dependence wherein

at least some dose intervals have a first portion characterized by an average electrical power, referred to as the first dose portion average power, and a second portion characterized by an average electrical power, referred to as the second dose portion average power, the first dose portion average power being different from the second dose portion average power, and

at least some burst intervals have a first portion characterized by a first average electrical power, referred to as the first burst portion average power, and a second portion characterized by a second average electrical power, referred to as the second burst portion average power, the first burst portion average power being different from the second burst portion average power.

38. The method of claim 62 wherein the burst intervals are triggered by a signal having a correlation with a cardiac cycle.

39. The method of claim 38 wherein the signal having a correlation with a cardiac cycle includes an ECG signal and/or a pressure pulse signal.

55. The method of claim 54, and further comprising positioning the baroreflex activation device proximate one or more baroreceptors.

56. The method of claim 54, and further comprising positioning the baroreflex activation device proximate one or more nerve fibers that carry signals from a baroreceptor to the brain.

57. The method of claim 54 wherein the difference between the first dose portion average power and the second dose portion average power is achieved by generating pulses in the first and second portions of the dose interval that differ in at least one of burst frequency, amplitude, and pulse width.

58. The method of claim 54 wherein the difference between the first burst portion average power and the second burst portion average power is achieved by generating pulses in the first and second portions of the burst interval that differ in at least one of burst frequency, amplitude, and pulse width.

59. The method of claim 54 wherein generating the electrical output signal comprises generating electrical pulses having one or more pulse characteristics chosen to provide said time dependence of electrical power applied to the baroreflex activation device.

60. The method of claim 59 wherein said pulse characteristics include one or more of pulse amplitude, pulse width, pulse frequency, pulse separation, pulse waveform, pulse polarity, and pulse phase.

61. The method of claim 54 wherein the therapy interval is on the order of minutes to hours.

62. The method of claim 54 wherein the burst intervals are commensurate with an interval between heartbeats.

63. The method of claim 62 wherein the burst intervals are triggered by a signal having a correlation with a cardiac cycle

64. The method of claim 63 wherein the signal having a correlation with a cardiac cycle includes an ECG signal and/or a pressure pulse signal.

65. The method of claim 54 wherein the therapy interval has a time dependence wherein a first portion is characterized by an average electrical power, referred to as the first therapy portion average power, over a first plurality of dose intervals, and a second portion characterized by an average electrical power, referred to as the second therapy portion average power, over a second plurality of dose intervals, the first therapy portion average power being different from the second therapy portion average power.

66. The method of claim 65 wherein the difference between the first therapy portion average power and the second therapy portion average power is achieved by generating pulses in the first and second portions of the therapy interval that differ in at least one of burst frequency, amplitude, and pulse width.

67. The method of claim 54 wherein the second dose portion average power is zero for at least some dose intervals.

68. The method of claim 54 wherein the second average burst power is zero for at least some burst intervals.

69. The method of claim 54 wherein a first set of the electrical pulses is applied to a first of a plurality of baroreflex activation devices and a second set of the electrical pulses is applied to a second of the plurality of baroreflex activation devices.

70. The method of claim 69, and further comprising establishing additional therapy intervals, wherein the first and second sets of electrical pulses are interleaved at the individual therapy interval level.

71. The method of claim 69 wherein the first and second sets of electrical pulses are interleaved at the dose interval level.

72. The method of claim 69 wherein the first and second sets of electrical pulses are interleaved at the burst interval level.

73. The method of claim 69 wherein the first and second sets of electrical pulses are interleaved at the pulse level.

74. The method of claim 54, and further comprising establishing additional therapy intervals, each of which has a first portion characterized by a first therapy portion average power over a first plurality of dose intervals and a second portion characterized by a second therapy portion average power over a second plurality of dose intervals, the first therapy portion average power being different from the second therapy portion average power.

75. The method of claim 54 wherein at least some therapy intervals differ from other therapy intervals.

76. The method of claim 54 wherein for at least some therapy intervals, the first portion is longer than the second portion.

79. A baroreflex activation system comprising:

a baroreflex activation device;

a control system configured to

establish a therapy interval,

establish, within the therapy interval, a plurality of dose intervals,

establish, within each dose interval, a plurality of burst intervals, and

generate an electrical output signal for application to the baroreflex activation device, the electrical signal being characterized in that electrical power applied to the baroreflex activation device has a time dependence as recited in claim 54;

and

an interconnection mechanism that applies the electrical output signal to the baroreflex activation device.

80. A system for generating an electrical control signal for application to a baroreflex activation device, the system including control circuitry configured to:

establish a therapy interval;

establish, within the therapy interval, a plurality of dose intervals; and

generate an electrical output signal characterized in that electrical power applied to the baroreflex activation device has a time dependence wherein at least some dose intervals have a first portion characterized by an average electrical power, referred to as the first dose portion average power, and a second portion characterized by an average electrical power, referred to as the second dose portion average power, the first dose portion average power being different from the second dose portion average power.

81. A system for generating an electrical control signal for application to a baroreflex activation device, the system including control circuitry configured to:

establish a series of therapy intervals;

establish, during at least some therapy intervals, a plurality of burst intervals; and

generate an electrical output signal characterized in that electrical power applied to the baroreflex activation device has a time dependence wherein

at least some therapy intervals have a first portion characterized by an average electrical power, referred to as the first therapy portion average power, and a second portion characterized by an average electrical power, referred to as the second therapy portion average power, the first therapy portion average electrical power being different from the second therapy portion average electrical power, and

at least some burst intervals have a first portion characterized by an average electrical power, referred to as the first burst portion average power, and a second portion characterized by an average electrical power, referred to as the second burst portion average power, the first burst portion average power being different from the second burst portion average power.

82. A system for generating an electrical control signal for application to a baroreflex activation device, the system including control circuitry configured to:

establish a therapy interval;

establish, within the therapy interval, a plurality of dose intervals;

establish, within each dose interval, a plurality of burst intervals; and

generate an electrical output signal characterized in that electrical power applied to the baroreflex activation device has a time dependence wherein

at least some dose intervals have a first portion characterized by an average electrical power, referred to as the first dose portion average power, and a second portion characterized by an average electrical power, referred to as the second dose portion average power, the first dose portion average power being different from the second dose portion average power, and

at least some burst intervals have a first portion characterized by a first average electrical power, referred to as the first burst portion average power, and a second portion characterized by a second average electrical power, referred to as the second burst portion average power, the first burst portion average power being different from the second burst portion average power.