Compositions, apparatus and methods for facilitating surgical procedures

• US 6,127,410 A
• Filed: 08/23/1999
• Issued: 10/03/2000
• 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:
  US09/379,179
• Time in Patent Office: 407 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 inducing transient reversible ventricular asystole in a human patient in which same is desired, comprising administering carbachol to the heart of the patient, while maintaining the ability of the heart to be electrically paced.

2. The method of claim 1 wherein the carbachol is administered to the coronary sinus.

3. The method of claim 1 wherein the carbachol is administered intraventricularly.

4. The method of claim 1 wherein the carbachol is administered to the aorta.

5. The method of claim 1 wherein the carbachol is administered to the right or left coronary artery.

6. The method of claim 1 wherein the method comprises administering carbachol and propranolol to the heart of the patient.

7. A method of inducing transient reversible ventricular asystole in the heart of a human patient in which same is desired, comprising administering carbachol to the patient at a dosage of about 1 to 15 mg, while maintaining the ability of the heart to be electrically paced.

8. The method of claim 7 wherein the dosage is about 1 to 12 mg.

9. A method of inducing transient reversible ventricular asystole in the heart of a human patient in which same is desired, the method comprising administering carbachol to the patient at a rate of about 0.1 to 4.8 μ

g/kg body weight/min, while maintaining the ability of the heart to be electrically paced.

10. The method of claim 9 wherein the carbachol is administered locally to the heart.

11. The method of claim 10 wherein the carbachol is administered by direct infusion into the right or left coronary artery.

12. A method of inducing transient reversible ventricular asystole in the heart of a human patient, in which same is desired, the method comprising:

administering an initial intracoronary bolus of carbachol of about 0.1 to 10 μ

g/kg body weight of the patient; and

administering a continuous intracoronary infusion of carbachol at a rate of about 0.1-4.8 μ

g/kg body weight/min, while maintaining the ability of the heart to be electrically paced.

13. The method of claim 12 wherein the initial intracoronary bolus of carbachol is administered over about 1-5 minutes;

and

wherein the intracoronary infusion of carbachol is administered over a time period of about 5 to 120 minutes.

14. The method of claim 13 wherein the initial intracoronary bolus comprises about 0.1 to 5 μ

g carbachol/kg body weight, and is provided in a suitable pharmaceutically acceptable carrier.

15. A method of inducing transient reversible ventricular asystole in a human patient in which same is desired, comprising:

administering an intracoronary bolus injection of about 0.01 to 0.5 mg of carbachol over about 0.5 to 3 minutes; and

administering an intracoronary infusion of carbachol at a rate of about 0.01 to 0.3 mg/min over about 30 to 90 minutes, while maintaining the ability of the heart to be electrically paced.