Rate control during AF using cellular intervention to modulate AV node

• US 20060247697A1
• Filed: 04/28/2005
• Published: 11/02/2006
• Est. Priority Date: 04/28/2005
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Sharma, Vinod, Sigg, Daniel C.
• Granted Patent: US 8,565,898 B2
• Time in Patent Office: Days
• US Class Current: 607/9
• CPC Class Codes: A61K 31/221 with compounds having an amino group, e.g. acetylcholine, acetylcarnitine
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61N 1/0568 with drug delivery
• CPC Class Codes: A61N 1/3629 in combination with non-electric therapy
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/06 Antiarrhythmics

Abstract

A biologic intervention method and apparatus generates a persistent modification to an AV node that is physiologically stable after the agent has matured but is alterable with subsequent application of an agent. Specifically, the generic agent is used to modulate a node in a cardiac conduction system including rate control using one and a combination of a family of K⁺ channel or equivalent. Specifically, the channel is implemented to slow conduction by generating an outward current during optimization of action potential and repolarization phase thus decreasing the current that is available to excite downstream cells. A Kv 1.3 channel, for example, may be used as the biologic channel. The invention enables reversal of the modulation or adjustment for various heart rates (BPM) based on medical and patient-specific needs.

Claims

1. A biologic intervention system to permanently modulate a cardiac conduction node, the system comprising:

means for titrating a dose of an exogenous gene; and

means for a backup pacing.

2. The system of claim 1 wherein said means for titrating includes means for measuring ERP.

3. The system of claim 1 wherein said means for titrating includes means for measuring the lowest pacing rate that produces Wenckebach phenomenon.

4. The system of claim 1 wherein said means for backup pacing includes a pacemaker to pace until an exogenous gene matures in the cardiac conduction node.

5. The system of claim 1 wherein said means for backup pacing includes a pacemaker to pace in the event of an exogenous gene overdose of the cardiac conduction node.

6. The system of claim 1 wherein said exogenous gene includes various Kv2 subunits and their regulatory subunits.

7. A biologic agent injected into a cardiac conduction node to modulate excitability of cardiac tissue comprising:

a plurality of biologic agents formed from a Kv1.3 channel; and

an injector for injecting the biologic agents into the conductor node.

8. The biologic agent of claim 7 selected from one of the family of Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw), Kv4 (Shal) and Kv5-9.

9. The biologic agent of claim 8 wherein at least one of the selected families includes one of mutated channels formed from the basal phosphorylation state and phosphorylation by enzymes such as protein kinase A (PKA) and protein B (PKB) altered or modified.

10. A method for manipulating cardiac conduction comprising:

introducing unexcitable cells in a cardiac conduction node; and

imposing a greater voltage load than in the conduction node to suppress charge transfer to an adjacent cell.

11. The method of claim 10 wherein said introducing includes transfecting fibroblasts with voltage gated potassium channels to produce outward current.

12. The method of claim 11 wherein said introducing includes performing EP study to determine ERP and measuring Wenckebach rate prior to injecting the unexcitable cells in the cardiac conduction node.

13. The method of claim 12 wherein said method of introducing includes titrating the dose of the gene based on the patient'"'"'s nodal modulation needs including heart rate (BPM) considerations to undertake various physical activities.

14. The method of claim 12 wherein said introducing depends on titrating the biologic agent on one of the ERP and the lowest pacing rate that produces Wenckebach phenomenon.

15. A system of introducing a genetic agent for cardiac node modulation, the system comprising:

means for delivering a bolus of drug to slow down conduction in the node; and

means for delivering the genetic agent to the node after confirmation of a slow down of conduction at the node.

16. The system of claim 15 wherein said bolus of drug includes a dose of acotylocholine.

17. The system of claim 15 wherein said genetic agent is selected from one of the family of Kv1, Kv2, Kv3, Kv4 and Kv5-9.

18. The system of claim 15 wherein said genetic agent is delivered to the AV node.

19. The system of claim 15 wherein a back-up pacemaker is connected and activated after delivery of a bolus drug and the genetic agent.

20. The system of claim 19 wherein said back-up pacemaker is activated if the biologic dose is high.