ERYTHROPOEITIN PRODUCTION BY ELECTRICAL STIMULATION

• US 20140288551A1
• Filed: 03/18/2014
• Published: 09/25/2014
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Pacesetter Incorporated (Abbott Laboratories)
• Original Assignee: Pacesetter Incorporated (Abbott Laboratories)
• Inventors: Bharmi, Rupinder, Rosenberg, Stuart, Rooke, Ryan, Karst, Edward, Farazi, Taraneh Ghaffari
• Granted Patent: US 9,610,444 B2
• Time in Patent Office: Days
• US Class Current: 606/41
• 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 2018/00404 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 5/02 Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
• CPC Class Codes: A61B 5/0205 Simultaneously evaluating both cardiovascular conditions and different types of body conditions, e.g. heart and respiratory condition
• CPC Class Codes: A61B 5/021 Measuring pressure in heart or blood vessels A61B5/0205 takes precedence
• CPC Class Codes: A61B 5/0215 by means inserted into the body catheters A61M25/00
• CPC Class Codes: A61B 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• CPC Class Codes: A61B 5/14535 for measuring haematocrit
• CPC Class Codes: A61B 5/14542 for measuring blood gases A61B5/14551 takes precedence
• CPC Class Codes: A61B 5/201 Assessing renal or kidney functions
• CPC Class Codes: A61B 5/4035 Evaluating the autonomic nervous system
• CPC Class Codes: A61B 5/486 Bio-feedback A61B5/375 takes precedence
• CPC Class Codes: A61N 1/36031 using physiological parameters for adjustment
• CPC Class Codes: A61N 1/36034 specified by the stimulation parameters
• CPC Class Codes: A61N 1/36053 adapted for vagal stimulation A61N1/36114 takes precedence
• CPC Class Codes: A61N 1/36121 Production of neurotransmitters; Modulation of genes expression
• CPC Class Codes: A61N 1/36125 Details of circuitry or electric components
• CPC Class Codes: A61N 1/36139 : with automatic adjustment
• CPC Class Codes: A61N 1/3702 : Physiological parameters A61N1/365 takes precedence; evoked response A61N1/371

Abstract

Described herein are methods, devices, and systems for treating human anemia. The methods, devices, and systems generally include monitoring a patients hemoglobin level and at least one of autonomic balance and inflammatory state to determine the etiology of the anemic state, modulating at least one of a sympathetic or parasympathetic nerve based on the cause of the anemia, monitoring for changes in the patients cardiac activity and state of inflammation, and hemoglobin level. An external neurostimulation system is describes, and well as a chronic implantable system. A method for treating a patient for anemia in conjunction with a renal denervation ablation catheter is also disclosed.

Claims

1. A method of treating anemia in a human patient, the method comprising:

monitoring the hemoglobin levels of the patient on a periodic basis;

determining an anemic condition based on the hemoglobin level;

selecting electrical stimulation parameters of a neurostimulation device based on one or more characteristics of the indicated anemic condition; and

generating one or more stimulation signals to stimulate the patient'"'"'s nervous system; and

monitoring at least one of an autonomic balance and inflammatory state of the patient resulting from the neurostimulation.

2. The method of claim 1 further comprising determining whether to provide stimulation of parasympathetic innervation, sympathetic innervation, or a combination of the two based on the anemic condition of the patient.

3. The method of claim 1 further comprising:

monitoring the patient'"'"'s cardiac activity; and

adapting the stimulation parameters based on the patient'"'"'s cardiac activity.

4. The method of claim 1, further comprising:

monitoring changes in at least one of;

a severity of the anemic condition, a patient'"'"'s heart rate, a quantity or severity of observed PVCs, and cardiac integrity; and

modifying stimulation parameters if there is a change in at least one of;

the severity of the anemic condition, the patient'"'"'s heart rate, the quantity or severity of observed PVCs, and the cardiac integrity.

5. The method of claim 1, wherein determining an anemic condition based on the hemoglobin level comprises determining the patient'"'"'s EPO observed/predicted (O/P) ratio.

6. The method of claim 1, wherein determining an anemic condition based on the hemoglobin level comprises determining the patient'"'"'s EPO observed/predicted O/P ratio, transferrin saturation, and ferritin level.

7. A system for treating anemia in a human patient comprising:

an external neural stimulator configured to stimulate at least one of a sympathetic and parasympathetic nerve in the patient'"'"'s neck or spine, wherein stimulation of the sympathetic nerve effects renal blood flow and stimulation of the parasympathetic nerve decreases the patient'"'"'s inflammation state;

an external cardiac sensor configured to monitor the patient cardiac activity, configured to provide the external neural stimulator with feedback for determining stimulation parameters.

8. The system of claim 7 further comprising a pulse generator configured to generate a pre-pulse prior to generating a therapeutic pulse to the neck or spinal cord in order to prepare the Na⁺ channels of neurons in the spinal cord and neck for activation.

9. A method comprising:

implementing a nerve stimulation therapy within a body that comprises delivering a therapeutic stimulation energy to a target nerve in order to stimulate EPO production;

temporarily halting the delivering therapeutic stimulation energy to the target nerve;

during the halting, delivering diagnostic stimulation energy to the target nerve;

acquiring a compound action potential responsive to the delivered non-therapeutic stimulation energy;

recommencing the delivering therapeutic stimulation energy to the target nerve; and

assessing a level of inflammation caused by the delivering therapeutic stimulation energy to the target nerve based at least in part on the acquired compound action potential.

10. The method of claim 9, further comprising initiating vagal nerve stimulation when the patient'"'"'s level of inflammation has increased above a threshold level.

11. A method of treating anemia in a human patient comprising:

ablating renal nerves of a patient using an ablation catheter;

permanently implanting one or more neuromodulation leads into the patient;

applying neurostimulation to at least one of a parasympathetic and sympathetic nerve using the neuromodulation lead to therapeutically treat the patient'"'"'s anemia.

12. The method of claim 11 wherein the lead is implanted into the renal vasculature of the patient, and wherein the neurostimulation is applied to the nerves of the renal vasculature.

13. The method of claim 11 wherein the ablation catheter is configured for both permanent ablation and non-permanent electrically modulate nerves.

14. The method of claim 11 further comprising using the one or more neuromodulation leads to neuromodulate the central nervous system in order to stimulate the production of catecholamines and neuropeptides.

15. The method of claim 11 further comprising using one or more neuromodulation leads to neuromodulate the vagal nerve of the patient in order to reduce inflammation and/or restore autonomic balance.

16. A method of triggering neurostimulation to treat anemia in a heart failure patient, the method comprising:

using a microprocessor within a neurostimulation device to determine triggering conditions, wherein the triggering conditions comprise;

the patient'"'"'s heart rate is within a specific heart range;

the patient'"'"'s heart condition is stable; and

cardiac ischemia is not ongoing; and

initiating neurostimulation using the neuromodulation device to treat anemia when the triggering conditions are determined to be met.

17. The method of claim 16, wherein neurostimulation comprises stimulation of a sympathetic nerve effecting EPO production.

18. The method of claim 16, wherein neuromodulation comprises stimulation of a parasympathetic nerve affecting inflammation.

19. The method of claim 16, wherein the parasympathetic nerve is the vagus nerve.

20. The method of claim 16, wherein the vagus nerve is a vagus nerve innervating the celiac-superior mesenteric plexus ganglion.

21. The method of claim 16, wherein the vagus nerve is a cervical vagus nerve.

22. The method of claim 16, wherein the triggering conditions further comprise:

bleeding is not ongoing.

23. The method of claim 16, wherein the triggering conditions further comprise:

a preprogrammed time of day.

24. The method of claim 16, further comprising obtaining cardiogenic impedance measurements from a plurality of vectors using a stimulation device to determining cardiac integrity and using cardiac integrity for feedback in determining stimulation parameters of the EPO stimulation.

25. A method of treating anemia in a human patient, the method comprising:

surgically implanting an electrode in communication with at least one predetermined site selected from the group consisting of one or more brain regions, a renal vessel, a carotid sinus nerve, one or more areas of the spinal cord, one or more vagus nerves;

therapeutically treating anemia by generating an electrical signal with the pulse generating source, wherein said signal electrically stimulates the at least one predetermined site;

determining an amount of inflammation caused by the electrical signal; and

automatically adjusting the control parameters and/or the predetermined site of stimulation of the pulse generating source based on at least the determined amount of inflammation.

26. The method of claim 25, wherein the at least one predetermined site comprises the NF-κ

B pathway of the hypothalamus, and wherein the electrical signal blocks the NF-κ

B pathway of the hypothalamus.

27. The method of claim 25, wherein the at least one predetermined site comprises an area of the spinal cord at T10-L2, the renal artery, the paraventricular nucleus of the hypothalamus, the cervical vagus nerve, and the NF-κ

B pathway of the hypothalamus.