Compositions, apparatus and methods for facilitating surgical procedures

• US 6,711,436 B1
• Filed: 09/27/1999
• Issued: 03/23/2004
• 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:
  US09/406,333
• Time in Patent Office: 1,639 Days
• Field of Search: 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: 607/9
• 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

Abstract

Methods are provided for conducting diagnostic or therapeutic medical or surgical procedures in a patient wherein, during the procedure, autonomous ventricular electrical conductivity and escape beats are reversibly and transiently suppressed to facilitate the procedure. Also provided are compositions which are capable of inducing ventricular asystole in a patient. The compositions may include an atrioventricular (AV) node blocker. In one embodiment, compositions including an 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 techniques, including minimally invasive microsurgical techniques. Methods for performing a diagnostic or therapeutic 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. In one embodiment, 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 diagnostic or therapeutic procedure, such as suturing, are conducted during the time that the electrical pacing is intermittently stopped. In one embodiment, pacing is not required, and at least one step of a procedure is conducted during a period of ventricular asystole. The methods and compositions advantageously may be used in a range of different diagnostic or therapeutic procedures including imaging procedures, placement of stents, grafts, and embolic devices, and cardiac, vascular and neurosurgical procedures.

Claims

1. A method of performing an aortic aneurysm repair procedure in which a graft member is positioned within a region of a patient'"'"'s aorta, comprising:

positioning a graft member within a patient'"'"'s aorta in a region of an aneurysm, and

inducing, prior to or during positioning the graft member in the aorta in a region of an aneurysm, at least one period of reversible ventricular asystole, while maintaining the ability of the heart to be electrically paced, wherein the period of asystole has a duration of more than approximately one minute.

2. The method of claim 1 wherein the graft is positioned in the region of the aneurysm during the at least one period of reversible ventricular asystole.

3. The method of claim 1 wherein the period of asystole has a duration of about 3 to 20 minutes.

4. The method of claim 1 wherein the period of asystole is induced by administering an AV node blocker and a β

-blocker to the heart at a sufficient dosage amount of each to induce asystole in the heart.

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

6. The method of claim 5 wherein the cholinergic receptor agonist comprises carbachol.

7. The method of claim 6 wherein the β

-blocker comprises propranolol.

8. The method of claim 4 further comprising electrically pacing the heart to maintain the patient'"'"'s blood circulation.

9. The method of claim 8 further comprising selectively intermittently stopping the electrical pacing during the asystole at least once for about 1 to 30 seconds prior to or during positioning the graft member in the region of the aneurysm.

10. The method of claim 4 wherein the β

-blocker is administered prior to the AV node blocker.

11. The method of claim 4 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.

12. The method of claim 4 wherein the AV node blocker and the β

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

13. The method of claim 12 wherein the AV node blocker and β

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

14. The method of claim 13 wherein the discharge opening is positioned in the right coronary artery proximate to the AV node artery.

15. The method of claim 13 wherein the drug delivery catheter is percutaneously inserted into the right coronary artery from a peripheral vascular access point.

16. The method of claim 15 wherein the peripheral vascular access point is a brachial artery.

17. The method of claim 15 wherein the peripheral vascular access point is a femoral artery.

18. The method of claim 15 wherein the peripheral vascular access point is a carotid artery.

19. The method of claim 15 wherein the peripheral vascular access point is a radial artery.

20. The method of claim 7 wherein the propranolol is administered as one or more bolus infusions at a total dosage amount of about 1 to 8 mg.

21. The method of claim 7 wherein the carbachol is administered as one or more initial bolus infusions at a total dosage amount of about 0.001 to 1.0 mg per bolus.

22. The method of claim 21 further comprising maintaining the period of asystole by administering a continuous intracoronary infusion of carbachol to the heart of the patient at a rate of about 0.001 to 0.3 mg/min over a time period of about 5 to 90 minutes.

23. A method of performing transmyocardial revascularization, comprising:

forming at least one blood flow channel in a wall of the heart of a patient, where the at least one blood flow channel has a fluid connection with a chamber of the heart, and

inducing, prior to or during formation of the channel, at least one period of reversible ventricular asystole, while maintaining the ability of the heart to be electrically paced, wherein the period of asystole has a duration of more than approximately one minute, and wherein the at least one blood flow channel is formed during the period of asystole.

24. The method of claim 23 wherein the period of asystole has a duration of about 3 to 20 minutes.

25. The method of claim 23 wherein the period of asystole is induced by administering an AV node blocker and a β

-blocker to the heart at a sufficient dosage amount of each to induce asystole in the heart.

26. The method of claim 25 wherein the AV node blocker comprises a cholinergic receptor agonist.

27. The method of claim 26 wherein the cholinergic receptor agonist comprises carbachol.

28. The method of claim 27 wherein the β

-blocker comprises propranolol.

29. The method of claim 25 further comprising electrically pacing the heart to maintain the patient'"'"'s blood circulation.

30. The method of claim 29 further comprising selectively intermittently stopping the electrical pacing during the asystole at least once for about 1 to 30 seconds prior to or during formation of the channel.

31. The method of claim 25 wherein the β

-blocker is administered prior to the AV node blocker.

32. The method of claim 25 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.

33. The method of claim 25 wherein the AV node blocker and the β

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

34. The method of claim 33 wherein the AV node blocker and β

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

35. The method of claim 34 wherein the discharge opening is positioned in the right coronary artery proximate to the AV node artery.

36. The method of claim 34 wherein the drug delivery catheter is percutaneously inserted into the right coronary artery from a peripheral vascular access point.

37. The method of claim 36 wherein the peripheral vascular access point is a brachial artery.

38. The method of claim 36 wherein the peripheral vascular access point is a femoral artery.

39. The method of claim 36 wherein the peripheral vascular access point is a carotid artery.

40. The method of claim 36 wherein the peripheral vascular access point is a radial artery.

41. The method of claim 28 wherein the propranolol is administered as one or more bolus infusions at a total dosage amount of about 1 to 8 mg.

42. The method of claim 28 wherein the carbachol is administered as one or more initial bolus infusions at a total dosage of about 0.001 to 1.0 mg per bolus.

43. The method of claim 42 further comprising maintaining the period of asystole by administering a continuous intracoronary infusion of carbachol to the heart of the patient at a rate of about 0.001 to 0.3 mg/min over a duration of about 5 to 90 minutes.

44. The method of claim 23 wherein the blood flow channel in the heart is formed by irradiating an exterior surface of the heart with laser energy.

45. The method of claim 23 wherein the blood flow channel in the heart is formed by irradiating an interior surface of the heart with laser energy.