HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dorman, B. H. Articles by Spinale, F. G. Search for Related Content PubMed PubMed Citation Articles by Dorman, B. H. Articles by Spinale, F. G.

J Thorac Cardiovasc Surg 1996;111:621-629
© 1996 Mosby, Inc.

CARDIOPULMONARY BYPASS, MYOCARDIAL MANAGEMENT, AND SUPPORT TECHNIQUES

PRESERVATION OF MYOCYTE CONTRACTILE FUNCTION AFTER HYPOTHERMIC, HYPERKALEMIC CARDIOPLEGIC ARREST WITH 2,3-BUTANEDIONE MONOXIME

Supported by National Institutes of Health Grant R29-HL-45024, a basic research grant from Pfizer, Inc., MUSC postdoctoral research award (M.J.C.), and South Carolina American Heart Association (B.H.D.). F.G.S. is an established investigator of the American Heart Association.

Received for publication April 4, 1995 Accepted for publication June 12, 1995. Address for reprints: B. Hugh Dorman, MD, PhD, Medical University of South Carolina, Department of Anesthesiology, 171 Ashley Ave., Charleston, SC 29425-2207.

Abstract

One proposed contributory mechanism for depressed ventricular performance after hypothermic, hyperkalemic cardioplegic arrest is a reduction in myocyte contractile function caused by alterations in intracellular calcium homeostasis. Because 2,3-butanedione monoxime decreases intracellular calcium transients, this study tested the hypothesis that 2,3-butanedione monoxime supplementation of the hyperkalemic cardioplegic solution could preserve isolated myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest. Myocytes were isolated from the left ventricles of six pigs. Magnitude and velocity of myocyte shortening were measured after 2 hours of incubation under normothermic conditions (37º C, standard medium), hypothermic, hyperkalemic cardioplegic arrest (4º C in Ringer's solution with 20 mEq potassium chloride), and hypothermic, hyperkalemic cardioplegic arrest with 2,3-butanedione monoxime supplementation (4º C in Ringer's solution with 20 mEq potassium chloride and 20 mmol/L 2,3-butanedione monoxime). Because ß-adrenergic agonists are commonly employed after cardioplegic arrest, myocyte contractile function was examined in the presence of the ß-agonist isoproterenol (25 nmol/L). Hypothermic, hyperkalemic cardioplegic arrest and rewarming reduced the velocity (32%) and percentage of myocyte shortening (27%, p < 0.05). Supplementation with 2,3-butanedione monoxime normalized myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest. Although ß-adrenergic stimulation significantly increased myocyte contractile function under normothermic conditions and after hypothermic, hyperkalemic cardioplegic arrest, contractile function of myocytes exposed to ß-agonist after hypothermic, hyperkalemic cardioplegic arrest remained significantly reduced relative to the normothermic control group. Supplementation with 2,3-butanedione monoxime restored ß-adrenergic responsiveness of myocytes after hypothermic, hyperkalemic cardioplegic arrest. Thus, supplementation of a hyperkalemic cardioplegic solution with 2,3-butanedione monoxime had direct and beneficial effects on myocyte contractile function and ß-adrenergic responsiveness after cardioplegic arrest. A potential mechanism for the effects of 2,3-butanedione monoxime includes modulation of intracellular calcium transients or alterations in sensitivity to calcium. Supplementation with 2,3-butanedione monoxime may have clinical utility in improving myocardial contractile function after hypothermic, hyperkalemic cardioplegic arrest. (J THORAC CARDIOVASC SURG 1996;111:621-9)

This article has been cited by other articles:

				J. Borlak and C. Zwadlo The Myosin ATPase Inhibitor 2,3-Butanedione monoxime Dictates Transcriptional Activation of Ion Channels and Ca2+-Handling Proteins Mol. Pharmacol., September 1, 2004; 66(3): 708 - 717. [Abstract] [Full Text] [PDF]

				F. G. Spinale Cellular and molecular therapeutic targets for treatment of contractile dysfunction after cardioplegic arrest Ann. Thorac. Surg., November 1, 1999; 68(5): 1934 - 1941. [Abstract] [Full Text] [PDF]

				J. R. Handy Jr., B. H. Dorman, M. J. Cavallo, R. B. Hinton, R. C. Roy, F. A. Crawford, and F. G. Spinale DIRECT EFFECTS OF OXYGENATED CRYSTALLOID OR BLOOD CARDIOPLEGIA ON ISOLATED MYOCYTE CONTRACTILE FUNCTION J. Thorac. Cardiovasc. Surg., October 1, 1996; 112(4): 1064 - 1072. [Abstract] [Full Text]