Compositions, apparatus and methods for facilitating surgical procedures

• US 6,414,018 B1
• Filed: 01/28/2000
• Issued: 07/02/2002
• Est. Priority Date: 08/08/1997
• Status: Expired due to Term

• Current Assignee: Duke University
• Original Assignee: Duke University
• Inventors: Duhaylongsod, Francis G.
• Primary Examiner(s): KRASS, FREDERICK F
• Application Number:
  US09/494,145
• Time in Patent Office: 886 Days
• Field of Search: 514/478, 514/479, 514/922, 607/9, 607/10, 607/11, 607/16, 607/27, 607/28, 607/30, 600/16, 600/17, 600/18, 604/507, 604/508, 604/509, 604/510, 604/96, 604/272, 604/523, 604/532
• US Class Current: 514/478
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/22 of acyclic acids, e.g. pravastatin
• CPC Class Codes: A61K 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61M 2210/125 Heart
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Abstract

Methods are provided for conducting surgical procedures in a patient wherein, during the surgical procedure, autonomous ventricular electrical conductivity and escape beats are reversibly and transiently suppressed to facilitate the surgical procedure. Also provided are compositions which are capable of inducing ventricular asystole in a patient. The compositions may include an AV node blocker. In one embodiment, compositions including an atrioventricular (AV) node blocker and a β-blocker are provided, wherein the β-blocker is present in an amount sufficient to substantially reduce the amount of AV node blocker required to induce ventricular asystole in the patient. The compositions and methods may be used for inducing temporary ventricular asystole in a beating heart, and to facilitate the performance of a variety of surgical techniques, including minimally invasive microsurgical techniques. Methods for performing a surgical procedure on a human patient are provided wherein a composition capable of inducing transient reversible ventricular asystole is administered to the heart, for example by intracoronary injection. The heart then is electrically paced using an electrical pacing system, thereby to maintain the patient'"'"'s blood circulation. The electrical pacing then is selectively intermittently stopped to allow ventricular asystole to occur, and the steps of the surgical or therapeutic procedure, such as suturing, are conducted during the time that the electrical pacing is intermittently stopped. The methods and compositions advantageously may be used in a range of different surgical procedures including cardiac, vascular and neurosurgical procedures.

Claims

1. A method of performing a medical procedure on a human patient comprising:

placing the patient on cardiopulmonary bypass support;

administering at least a first agent to the heart of the patient which is capable of inducing at least one period of reversible ventricular asystole of the heart, while maintaining the ability of the heart to be electrically paced; and

performing at least one step of the medical procedure during the at least one period of ventricular asystole;

said method further comprising electrically pacing the heart at least once during the medical procedure.

2. The method of claim 1 wherein the at least one period of ventricular asystole has a duration of between about 30 to 90 minutes.

3. The method of claim 2 wherein the at least one period of ventricular asystole has a duration of between about 30 to 45 minutes.

4. The method of claim 1 wherein the administration of at least a first agent to the heart of the patient comprises administering an AV node blocker to the heart at a sufficient dosage amount to induce at least one period of reversible ventricular asystole of the heart.

5. The method of claim 4 further comprising administering a β

-blocker to the patient.

6. The method of claim 5 wherein the β

-blocker is administered to the heart of the patient.

7. The method of claim 4 wherein the AV node blocker comprises a cholinergic receptor agonist.

8. The method of claim 7 wherein the cholinergic receptor agonist comprises carbachol.

9. The method of claim 8 wherein the carbachol is administered in an amount of about 0.1 to 4.8 μ

g/kg body weight/min.

10. The method of claim 5 wherein the β

-blocker comprises propranolol.

11. The method of claim 10, wherein the propranolol is administered in an amount of about 0.01 to 0.07 mg/kg body weight.

12. The method of claim 6 wherein the β

-blocker is administered prior to the AV node blocker.

13. The method of claim 6 wherein the β

-blocker is administered in an amount sufficient to substantially reduce the amount of AV node blocker required to induce asystole of the heart.

14. The method of claim 6 wherein the AV node blocker and the β

-blocker are administered to the right or left coronary artery of the heart.

15. The method of claim 14 wherein the AV node blocker and the β

-blocker are administered to the right or left coronary artery through a drug delivery catheter which has at least one outlet which is positioned in the right or left coronary artery.

16. The method of claim 15 wherein the outlet is positioned in the right coronary artery proximate to the AV node artery.

17. The method of claim 15 wherein the drug delivery catheter is percutaneously inserted into the right coronary artery from a peripheral vascular access point.

18. The method of claim 17 wherein the peripheral vascular access point is a femoral artery.

19. The method of claim 17 wherein the peripheral vascular access point is a radial artery.

20. The method of claim 1 wherein the agent is delivered by needle injection into a coronary vessel.

21. The method of claim 1 wherein the medical procedure is a coronary artery bypass graft procedure.

22. The method of claim 21, wherein the coronary artery bypass graft procedure avoids the use of an aortic cross-clamp.

23. The method of claim 1 wherein the medical procedure is a valve procedure.