Neuromodulation of baroreceptor reflex

Patent metadata

Field	Value
Publication number	US-2023381519-A1
Application number	US-202318158563-A
Country	US
Kind code	A1
Filing date	Jan 24, 2023
Priority date	Sep 14, 2017
Publication date	Nov 30, 2023
Grant date	—

Abstract

Modulation of neural activity of a subject's aortic depressor nerve (ADN) and/or carotid sinus nerve (CSN) can modulate baroreceptor reflex function, thereby providing ways of treating or preventing disorders associated with malfunction or loss of the baroreceptor reflex.

First claim

1 . A system for modulating neural activity in a subject's aortic depressor nerve (ADN) and/or carotid sinus nerve (CSN), the system comprising:
at least one neural interfacing element having at least one electrode configured to be in signaling contact with the ADN and/or CSN that is being modulated, and a signal generator comprising at least one voltage or current source configured to generate at least one signal to be applied to the ADN and/or CSN that is being modulated via the at least one electrode to modulate the neural activity of the ADN and/or CSN that is being modulated to produce a change in a physiological parameter in the subject, wherein the amplitude of the at least one signal is ≤0.4 mA; wherein the change in the physiological parameter is one or more of the group consisting of: a decrease in mean arterial pressure, a decrease in heart rate, an increase in minute ventilation, an improvement in regularity of a heart rhythm, an improvement in heart conduction, an increase in heart contractility, a decrease in vascular resistance, an increase in cardiac output, an increase in blood flow, an increase in minute ventilation, an increase in a hemodynamic response, a decrease in a chronotropic evoked response, a decrease in a dromotropic evoked response, a decrease in a lusitropic evoked response, a decrease in an inotropic evoked response, and a decrease in pain perception; wherein the signal generator is controlled to deliver to the ADN and/or CSN that is being modulated the at least one signal having a total intensity, the total intensity being below a predetermined threshold, the predetermined threshold defined as the total intensity of a signal required to be received by the ADN and/or CSN to produce a ≤30 mmHg drop in the mean arterial blood pressure.

2 . The system of claim 1 , wherein the at least one signal is configured to be applied to the ADN, and the at least one electrode is suitable for placement on or around the ADN.

3 . The system of claim 1 , wherein the at least one signal is configured to be applied to the CSN, wherein the at least one electrode is suitable for placement on or around the CSN.

4 . The system of claim 1 , wherein the at least one signal includes a first signal and a second signal, the first signal is configured to be applied to the ADN and the second signal is configured to be applied to the CSN, wherein the at least one electrode includes a first electrode and a second electrode, the first electrode is suitable for placement on or around the ADN and the second electrode is suitable for placement on or around the CSN, wherein the first signal is to be applied via the first electrode and the second signal is to be applied via the second electrode.

5 . The system of claim 1 , wherein the at least one signal is configured to be applied to the ADN and/or CSN unilaterally or bilaterally.

6 . The system of claim 4 , wherein the at least one signal is configured to be applied to the ADN and the CSN ipsilaterally.

7 . The system of claim 1 , wherein the predetermined threshold is ≤30 μAs.

8 . The system of claim 1 , wherein the total intensity of the signal is between 0.1 TINT and 0.9 TINT, where TINT is the predetermined threshold.

9 . The system of claim 1 , wherein the at least one signal has a predetermined duty cycle of ≤65%.

10 . The system of claim 1 , wherein the at least one signal has a pulse width of ≤1 ms.

11 . The system of claim 1 , wherein the frequency of the at least one signal is ≤70 Hz.

12 . The system of claim 1 , wherein the at least one signal is applied in a (ONy−OFFz)n pattern where n>1, y>0, and z>0, and the at least one signal is applied for: (a) ≤20 s, or (b) ≤30 min at any given time up to 12 times a day.

13 . The system of claim 1 , wherein the signal generator is controlled to deliver the at least one signal during a specific time of a day.

14 . The system of claim 1 , further comprising a detector configured to:
detect one or more signals indicative of one or more second physiological parameters; determine from the one or more signals the one or more second physiological parameters; determine the one or more second physiological parameters indicative of worsening of the second physiological parameter; and cause the at least one signal to be applied to the ADN and/or CSN via the at least one electrode, wherein the second physiological parameter is one or more of the group consisting of: systemic arterial blood pressure, heart rate, heart rhythm, electrical conduction in the heart and heart contractility, vascular resistance, cardiac output, rate of blood flow, minute ventilation, and pain perception.

15 . The system of claim 14 , further comprising a memory arranged to store data pertaining to the second physiological parameters indicative of a disorder associated with malfunction or loss of the baroreceptor reflex, wherein determining the one or more second physiological parameters indicative of worsening of the second physiological parameter comprises comparing the one or more second physiological parameters with the data.

16 . The system of claim 14 , wherein one of the second physiological parameters is the arterial blood pressure, wherein the detector comprises a pressure sensor.

17 . A method of treating or preventing a disorder associated with malfunction or loss of a baroreceptor reflex in a subject by reversibly modulating neural activity of a subject's aortic depressor nerve (ADN) and/or carotid sinus nerve (CSN), comprising: implanting in the subject the system of claim 1 ; positioning the neural interfacing element in signaling contact with the ADN and/or CSN; and optionally activating the system to provide at least one signal wherein the at least one signal is applied to the ADN and/or the CSN.

18 . The method of claim 17 , wherein the method is for treating or preventing a cardiovascular disorder and a disorder associated therewith, or a cardiorespiratory and a disorder associated therewith.

19 . A method for treating or preventing a disorder associated with malfunction or loss of a baroreceptor reflex, comprising:
applying a signal to a subject's aortic depressor nerve (ADN) and/or carotid sinus nerve (CSN) via at least one neural interfacing element having at least one electrode in signaling contact with the ADN and/or CSN, such that the signal reversibly modulates neural activity of the ADN and/or CSN to produce a change in a physiological parameter in the subject: wherein the change in the physiological parameter is one or more of the group consisting of: a decrease in mean arterial pressure, a decrease in heart rate, an increase in minute ventilation, an improvement in the regularity of the a heart rhythm, an improvement in heart conduction, an increase in heart contractility, a decrease in vascular resistance, an increase in cardiac output, an increase in blood flow, an increase in minute ventilation, an increase in a hemodynamic response, a decrease in a chronotropic evoked response, a decrease in a dromotropic evoked response, a decrease in a lusitropic evoked response, a decrease in an inotropic evoked response, and a decrease in pain perception,
wherein the total intensity of the signal received by the ADN and/or CSN that is being modulated is below a predetermined threshold, the predetermined threshold defined as the total intensity of a signal required to be received by the ADN and/or CSN to produce a ≤30 mmHg drop in the mean arterial blood pressure: and wherein the amplitude of the at least one signal is ≤0.4 mA.

Assignees

• Univ Case Western Reserve
• Galvani Bioelectronics Ltd

Inventors

• Sridhar Arun
• Lewis Stephen J
• Salman Ibrahim

Classifications

• A61N1/36139 Primary

  with automatic adjustment · CPC title

• A61N1/36117

  for treating hypertension · CPC title

• A61N1/36157

  Current (A61N1/3616 takes precedence) · CPC title

• A61N1/36175

  Pulse width or duty cycle · CPC title

• A61N1/36178

  Burst or pulse train parameters · CPC title