Method for reversibly arresting muscle activity

• US 5,162,374 A
• Filed: 06/12/1991
• Issued: 11/10/1992
• Est. Priority Date: 11/01/1989
• Status: Expired due to Fees

• Current Assignee: University of Vermont & State Agricultural College
• Original Assignee: University of Vermont & State Agricultural College
• Inventors: Hasenfuss, Gerd, Mulieri, Louis A., Alpert, Norman R.
• Primary Examiner(s): Raymond, Richard L.
• Assistant Examiner(s): HOLLINDEN, GARY E
• Application Number:
  US07/714,333
• Time in Patent Office: 517 Days
• Field of Search: 514/640, 514/906
• US Class Current: 514/640
• CPC Class Codes: A01N 1/0226 Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
• 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 31/15 Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
• CPC Class Codes: A61K 38/28 Insulins

Abstract

Muscle activity can be reversibly arrested by administering a reagent, such as 2,3-butanedione monoxime (BDM), which selectively blocks the interaction of the contractile proteins actin and myosin. Muscle such as the heart is contacted with the reagent to arrest activity and, after surgery or transplantation, the reagent is removed from the muscle to restore muscle activity. The preferred reagent BDM has the following structure: ##STR1##

Claims

1. A method for reversibly arresting human cardiac muscle activity comprising the steps of:

a. contacting cardiac muscle tissue with an effective amount of a diffusible, non-toxic chemical agent which selectively and reversibly blocks the interaction of the contractile proteins actin and myosin thereby eliminating contraction and its associated consumption of energy; and

b. following a selected amount of time, removing an amount of the chemical agent form contact with the cardiac muscle tissue sufficient to restore the muscle activity.

2. The method of claim 1, wherein the chemical agent is 2,3-Butanedione monoxime or homologues thereof.

3. A method of reversible cardioplegia for heart transplantation, comprising the steps of:

a. contacting a human donor heart with an effective cardioplegic amount of 2,3-Butanedione monoxime;

b. maintaining the heart in contact with the 2,3-Butanedione monoxime; and

c. surgically introducing the heart into a recipient patient and removing the 2,3-Butanedione monoxime from the heart to reverse the cardioplegia.

4. The method of claim 3, wherein the 2,3-butanedione monoxime is introduced into coronary circulation to induce the cardioplegia.

5. A method of claim 3, wherein the myocardium is immersed into a physiologically acceptable solution comprising an effective cardioplegic amount of 2,3-butanedione monoxime or a homologue thereof.

6. The method of claim 3, wherein 2,3-butanedione is in a physiologically acceptable solution.

7. A method of claim 6, wherein the solution comprises Na⁺, K⁺, Cl^-, HCO₃^-, Mg²⁺, H₂ PO^4- SO₄^2- Ca²⁺ and glucose.

8. A method of claim 3, further comprising reversing the cardioplegia by removing the 2,3-butanedione from contact with the myocardium.