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 Author home page(s): Fred A. Crawford, Jr. Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by O, S.-J. Articles by Spinale, F. G. Search for Related Content PubMed PubMed Citation Articles by O, S.-J. Articles by Spinale, F. G.

J Thorac Cardiovasc Surg 1997;114:651-659
© 1997 Mosby, Inc.

CARDIOPULMONARY BYPASS, MYOCARDIAL MANAGEMENT, AND SUPPORT TECHNIQUES

PROTEIN KINASE C ACTIVATION BEFORE CARDIOPLEGIC ARREST: BENEFICIAL EFFECTS ON MYOCYTE CONTRACTILITY

Supported by National Institutes of Health grant HL-45024, a Basic Research Grant from Pfizer Inc., a Grant-in-Aid from the South Carolina Heart Association, and a Grant-in-Aid from the American Heart Association. M. H. C. performed this work as a Medical Student Research Fellow of the American Heart Association. F. G. S. is an Established Investigator of the American Heart Association.

Received for publication August 6, 1996 revisions requested Dec. 5, 1996; revisions received April 21, 1997 accepted for publication April 22, 1997. Address for reprints: Francis G. Spinale, MD, PhD, Cardiothoracic Surgery, Room 418 CSB, Medical University of South Carolina, 171 Ashley Ave., Charleston, SC 29425.

Abstract

Objective: A potential intracellular mechanism for the protective effects of myocardial preconditioning is the activation of protein kinase C. The present study tested the hypothesis that a brief period of protein kinase C activation before cardioplegic arrest would provide protective effects on myocyte contractility with subsequent reperfusion and rewarming. Methods: Left ventricular porcine myocytes were assigned to the following treatments: (1) Protein kinase C/cardioplegia: Protein kinase C activation in myocytes (n = 39) for 3 minutes with a phorbol ester (10^-9 mol/L of phorbol 12-myristate 13-acetate) in oxygenated, normothermic (37° C) cell media. Protein kinase C activation was followed by 2 hours of cardioplegic arrest (K⁺, 24 mEq/L; HCO₃ ^–, 30 mEq/L; 4° C) and a 5-minute reperfusion period (37° C media). (2) Cardioplegia: Myocytes (n = 31), 2 hours of cardioplegic arrest, and a 5-minute reperfusion and rewarming period. Myocyte contractility was measured by means of high-speed videomicroscopy. For comparison purposes, contractile function was examined in myocytes (n = 70) under normothermic control conditions. Results: Myocyte shortening velocity was reduced after cardioplegic arrest when compared with normothermic values (22.3 ± 1.6 vs 48.8 ± 2.0 µm/sec, p < 0.0001). Protein kinase C activation before cardioplegic arrest normalized myocyte shortening velocity (48.8 ± 2.5 µm/sec). Co-incubation with phorbol 12-myristate 13-acetate and chelerythrine (10^-6 mol/L), an inhibitor of protein kinase C, before cardioplegic arrest abolished the protective effects of phorbol 12-myristate 13-acetate pretreatment. Conclusion: These results suggest that an endogenous means of providing improved myocardial protection during prolonged cardioplegic arrest can be achieved through a brief period of protein kinase C activation.

This article has been cited by other articles:

				A. M. Deschamps, J. Zavadzkas, R. L. Murphy, C. N. Koval, J. E. McLean, L. Jeffords, S. M. Saunders, N. J. Sheats, R. E. Stroud, and F. G. Spinale Interruption of endothelin signaling modifies membrane type 1 matrix metalloproteinase activity during ischemia and reperfusion Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H875 - H883. [Abstract] [Full Text] [PDF]

				M. L. Coker, J. R. Jolly, C. Joffs, T. Etoh, J. R. Holder, B. R. Bond, and F. G. Spinale Matrix metalloproteinase expression and activity in isolated myocytes after neurohormonal stimulation Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H543 - H551. [Abstract] [Full Text] [PDF]

				C. Stamm, I. Friehs, D. B. Cowan, H. Cao-Danh, S. Noria, M. Munakata, F. X. McGowan Jr., and P. J. del Nido Post-ischemic PKC inhibition impairs myocardial calcium handling and increases contractile protein calcium sensitivity Cardiovasc Res, July 1, 2001; 51(1): 108 - 121. [Abstract] [Full Text] [PDF]

				A. T. Goldberg, B. R. Bond, R. Mukherjee, R. B. New, J. L. Zellner, F. A. Crawford Jr, and F. G. Spinale Endothelin receptor pathway in human left ventricular myocytes: relation to contractility Ann. Thorac. Surg., March 1, 2000; 69(3): 711 - 715. [Abstract] [Full Text] [PDF]

				D. Belhomme, J. Peynet, M. Louzy, J.-M. Launay, M. Kitakaze, and P. Menasche Evidence for Preconditioning by Isoflurane in Coronary Artery Bypass Graft Surgery Circulation, November 9, 1999; 100(90002): II-340 - 344. [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]

				B. Z. Simkhovich, K. Przyklenk, and R. A. Kloner Role of protein kinase C as a cellular mediator of ischemic preconditioning: a critical review Cardiovasc Res, October 1, 1998; 40(1): 9 - 22. [Abstract] [Full Text] [PDF]