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

This Article Full Text Full Text (PDF) 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): Yoshiya Toyoda Sidney Levitsky Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wakiyama, H. Articles by McCully, J. D. Search for Related Content PubMed PubMed Citation Articles by Wakiyama, H. Articles by McCully, J. D. Related Collections Myocardial infarction

Eur J Cardiothorac Surg 2002;21:424-433
© 2002 Elsevier Science NL

Selective opening of mitochondrial ATP-sensitive potassium channels during surgically induced myocardial ischemia decreases necrosis and apoptosis

Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Room 144, Boston, MA 02115, USA

Received 27 September 2001; received in revised form 8 December 2001; accepted 12 December 2001.

* Corresponding author. Tel.: +1-617-667-0725; fax: +1-617-975-5245
e-mail: james_mccully{at}hms.harvard.edu

Objective: Mitochondrial ATP-sensitive potassium channels have been proposed to be myoprotective. The relevance and specificity of this mechanism in cardiac surgery was unknown. The purpose of this study was to examine the effects of the mitochondrial potassium ATP-sensitive channel opener diazoxide on regional and global myocardial protection using a model of acute myocardial infarction. Methods: Pigs (n=19) were placed on total cardiopulmonary bypass and then subjected to 30 min normothermic regional ischemia by snaring the left anterior descending coronary artery (LAD). The aorta was then crossclamped and cold blood Deaconess Surgical Associates cardioplegia (DSA; n=6) or DSA containing 50 µM diazoxide (DZX; n=6) was delivered via the aortic root and the hearts subjected to 30 min hypothermic global ischemia. The crossclamp and snare were removed and the hearts reperfused for 120 min. Results: No significant differences in preload recruitable stroke work relationship, Tau, proximal, distal or proximal/distal coronary flow, regional or global segmental shortening, systolic bulging or post-systolic shortening were observed within or between DSA and DZX hearts during reperfusion. Infarct was present only in the region of LAD occlusion in both DSA and DZX hearts. Infarct size (% of area at risk) was 33.6±2.9% in DSA and was 16.8±2.4% in DZX hearts (P<0.01 versus DSA). Apoptosis as estimated by TUNEL positive nuclei was 120.3±48.8 in DSA and was significantly decreased to 21.4±5.3 in DZX hearts. Myocardial infarct was located centrally within the area at risk in both DSA and DZX hearts but was significantly increased at borderline zones within the area at risk in DSA hearts. Conclusions: The addition of diazoxide to cardioplegia significantly decreases regional myocardial cell necrosis and apoptosis in a model of acute myocardial infarction and represents an additional modality for achieving myocardial protection.

Key Words: Mitochondrial ATP-sensitive potassium (mitoK_ATP) channels • Myocardial cell necrosis • Apoptosis • Cardioplegia • Surgery

This article has been cited by other articles:

				J. D. McCully, M. K. Bhasin, C. Daly, M. C. Guerrero, S. Dillon, T. A. Liberman, D. B. Cowan, J. D. Mably, F. X. McGowan, and S. Levitsky Transcriptomic and proteomic analysis of global ischemia and cardioprotection in the rabbit heart Physiol Genomics, July 9, 2009; 38(2): 125 - 137. [Abstract] [Full Text] [PDF]

				J. D. McCully, D. B. Cowan, C. A. Pacak, I. K. Toumpoulis, H. Dayalan, and S. Levitsky Injection of isolated mitochondria during early reperfusion for cardioprotection Am J Physiol Heart Circ Physiol, January 1, 2009; 296(1): H94 - H105. [Abstract] [Full Text] [PDF]

				Y.-J. Hsieh, H. Wakiyama, S. Levitsky, and J. D. McCully Cardioplegia and Diazoxide Modulate STAT3 Activation and DNA Binding Ann. Thorac. Surg., October 1, 2007; 84(4): 1272 - 1278. [Abstract] [Full Text] [PDF]

				L. Wang, C. Kinnear, J. M. Hammel, W. Zhu, Z. Hua, W. Mi, and C. A. Caldarone Preservation of Mitochondrial Structure and Function After Cardioplegic Arrest in the Neonate Using a Selective Mitochondrial K(ATP) Channel Opener. Ann. Thorac. Surg., May 1, 2006; 81(5): 1817 - 1823. [Abstract] [Full Text] [PDF]

				Z.-Q. Zhao and J. Vinten-Johansen Postconditioning: Reduction of reperfusion-induced injury Cardiovasc Res, May 1, 2006; 70(2): 200 - 211. [Abstract] [Full Text] [PDF]

				M. A. Deja, K. S. Golba, M. Malinowski, K. Widenka, J. Biernat, D. Szurlej, and S. Wos Diazoxide Provides Maximal KATP Channels Independent Protection if Present Throughout Hypoxia Ann. Thorac. Surg., April 1, 2006; 81(4): 1408 - 1416. [Abstract] [Full Text] [PDF]

				T. Vahasilta, A. Saraste, V. Kyto, M. Malmberg, J. Kiss, E. Kentala, M. Kallajoki, and T. Savunen Cardiomyocyte Apoptosis After Antegrade and Retrograde Cardioplegia Ann. Thorac. Surg., December 1, 2005; 80(6): 2229 - 2234. [Abstract] [Full Text] [PDF]

				A. J. Rousou, M. Ericsson, M. Federman, S. Levitsky, and J. D. McCully Opening of mitochondrial KATP channels enhances cardioprotection through the modulation of mitochondrial matrix volume, calcium accumulation, and respiration Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H1967 - H1976. [Abstract] [Full Text] [PDF]

				T. M. Scarabelli, E. Pasini, G. Ferrari, M. Ferrari, A. Stephanou, K. Lawrence, P. Townsend, C. Chen-Scarabelli, G. Gitti, L. Saravolatz, et al. Warm blood cardioplegic arrest induces mitochondrial-mediated cardiomyocyte apoptosis associated with increased urocortin expression in viable cells J. Thorac. Cardiovasc. Surg., September 1, 2004; 128(3): 364 - 371. [Abstract] [Full Text] [PDF]

				J. D. McCully, H. Wakiyama, Y.-J. Hsieh, M. Jones, and S. Levitsky Differential contribution of necrosis and apoptosis in myocardial ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1923 - H1935. [Abstract] [Full Text] [PDF]

				A. Anselmi, A. Abbate, F. Girola, G. Nasso, G. G.L. Biondi-Zoccai, G. Possati, and M. Gaudino Myocardial ischemia, stunning, inflammation, and apoptosis during cardiac surgery: a review of evidence Eur. J. Cardiothorac. Surg., March 1, 2004; 25(3): 304 - 311. [Abstract] [Full Text] [PDF]

				M. A. Deja, K. S. Golba, M. Kolowca, K. Widenka, J. Biernat, and S. Wos Diazoxide provides protection to human myocardium in vitro that is concentration dependent Ann. Thorac. Surg., January 1, 2004; 77(1): 226 - 232. [Abstract] [Full Text] [PDF]

				X. Wang, M. Wei, P. Kuukasjarvi, J. Laurikka, O. Jarvinen, T. Rinne, E.-L. Honkonen, and M. Tarkka Novel pharmacological preconditioning with diazoxide attenuates myocardial stunning in coronary artery bypass grafting Eur. J. Cardiothorac. Surg., December 1, 2003; 24(6): 967 - 973. [Abstract] [Full Text] [PDF]

				G. Valen The basic biology of apoptosis and its implications for cardiac function and viability Ann. Thorac. Surg., February 1, 2003; 75(2): S656 - 660. [Abstract] [Full Text] [PDF]

				J. D. McCully and S. Levitsky The mitochondrial KATP channel and cardioprotection Ann. Thorac. Surg., February 1, 2003; 75(2): S667 - 673. [Abstract] [Full Text] [PDF]

				J. D. McCully, H. Wakiyama, D. B. Cowan, M. Federman, R. A. Parker, and S. Levitsky Diazoxide amelioration of myocardial injury and mitochondrial damage during cardiac surgery Ann. Thorac. Surg., December 1, 2002; 74(6): 2138 - 2146. [Abstract] [Full Text] [PDF]