Compositions, apparatus and methods for facilitating surgical procedures

• US 6,043,273 A
• Filed: 08/23/1999
• Issued: 03/28/2000
• 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:
  US09/379,180
• Time in Patent Office: 218 Days
• Field of Search: 514/26, 514/46, 514/211, 514/222.5, 514/226.2, 514/236.2, 514/258, 514/260, 514/311, 514/314, 514/317, 514/327, 514/331, 514/346, 514/347, 514/397, 514/415, 514/470 , 514/473, 514/478, 514/479, 514/523, 514/535, 514/537, 514/538, 514/605, 514/617, 514/620, 514/642, 514/651, 514/652, 514/653, 514/654, 514/655, 514/663, 514/667, 514/92 2, 600/16, 600/19, 604/264, 604/272, 604/523, 604/532, 604/536, 607/9, 607/30, 607/32
• 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 composition suitable for administration to the heart of a human patient and capable of inducing transient reversible ventricular asystole in a human patient, while maintaining the ability of the heart to be electrically paced, comprising:

a compound capable of inducing reversible ventricular asystole in a patient; and

a β

-blocker in an amount sufficient to substantially reduce the amount of the compound required to induce ventricular asystole in the patient.

2. The composition of claim 1 wherein the compound is an atrioventricular (AV) node blocker.

3. The composition of claim 2, wherein the AV node blocker is present in an amount which is about 50% or less by weight of the amount of AV node blocker alone required to induce ventricular asystole.

4. The composition according to claim 1, wherein the compound is a cholinergic receptor agonist selected from the group consisting of bethanechol, arecoline, norarecoline, and neostigmine.

5. The composition according to claim 1, wherein the compound is carbachol.

6. The composition according to claim 5, wherein the carbachol is present in a pharmaceutically acceptable carrier in a dosage form for administration to a patient.

7. The composition according to claim 5, wherein the carbachol is present in a pharmaceutically acceptable solution at a dosage amount of about 1 to 20 mg.

8. The composition according to claim 1, wherein the β

-blocker is selected from the group consisting of atenolol, acebutolol, labetalol, metoprolol, nadolol, oxprenolol, penbutolol, pindolol, sotalol, timolol, celiprolol, betaxolol, bevantolol, bisoprolol, esmolol, alprenolol, carterolol, nadolol and teratolol.

9. The composition according to claim 1, wherein the β

-blocker is propranolol.

10. The composition according to claim 9, wherein the propranolol is present in a pharmaceutically acceptable carrier in a dosage form for administration to a patient in an amount of about 0.01 to 0.07 mg/kg body weight of the patient.

11. The composition according to claim 9, wherein the propranolol is present in a pharmaceutically acceptable solution at a dosage amount of about 1 to 10 mg.

12. The composition according to claim 1, wherein the compound is carbachol and the β

-blocker is propranolol.

27. The composition of claim 1, wherein said compound is a cholinergic receptor agonist.

13. A composition suitable for administration to the heart of a human patient and capable of inducing ventricular asystole in a human patient, while maintaining the ability of the heart to be electrically paced, comprising:

a cholinergic receptor agonist; and

a β

-blocker;

wherein the amount of the cholinergic receptor agonist alone or the β

-blocker alone in the composition is not sufficient to induce ventricular asystole in the patient.

14. A kit for conducting a medical procedure on a human patient comprising:

a first container comprising a cholinergic receptor agonist; and

a second container comprising a β

-blocker wherein the cholinergic receptor agonist and beta-blocker are present in a form suitable for administration to the heart of a human patient and are capable of inducing transient reversible ventricular asystole in the patient'"'"'s heart, while maintaining the ability of the heart to be electrically paced, and the beta blocker is present in an amount sufficient to substantially reduce the amount of the cholinergic receptor agonist required to induce ventricular asystole in the patient.

15. The kit according to claim 14, wherein the cholinergic receptor agonist is carbachol and the β

-blocker is propranolol.

16. The kit according to claim 15, wherein the first container comprises carbachol in a pharmaceutically acceptable carrier;

and

wherein the second container comprises propranolol in a pharmaceutically acceptable carrier.

17. The kit according to claim 16, wherein

the first container contains about 1 to 20 mg of carbachol;

and

wherein the second container contains about 1 to 10 mg of propranolol.

18. The kit according to claim 15 further comprising epicardial or endocardial pacing electrodes.

19. The kit according to claim 15 further comprising a drug delivery catheter.

20. The kit according to claim 19 wherein said drug delivery catheter further includes an expandable member, said catheter including a shaft having a distal portion and said expandable member being disposed along said distal portion.

21. The kit according to claim 20 wherein said expandable member comprises a low-pressure balloon.

22. The kit according to claim 14 further comprising a guide catheter.

23. The kit according to claim 14 further comprising a cannula.

24. The kit according to claim 14 further comprising a syringe and needle assembly.

25. A kit having instructions for use in inducing transient reversible ventricular asystole in a human patient, comprising:

a first container comprising a cholinergic receptor agonist; and

a second container comprising a beta-blocker.

26. The kit of claim 25, wherein said cholinergic receptor agonist is carbachol and said beta-blocker is propranolol.