AJP - Heart and Circulatory Physiology, Vol 266, Issue 3 1145-H1152, Copyright © 1994 by American Physiological Society

ARTICLES

Preconditioning protects ischemic rabbit heart by protein kinase C activation

K. Ytrehus, Y. Liu and J. M. Downey
Department of Medical Physiology, University of South Alabama, Mobile 36688.

Myocardial protection in the rabbit induced by ischemic preconditioning is thought to be adenosine receptor linked, but the signaling pathway responsible for the protection has yet to be identified. This study tests whether protein kinase C could be involved. Either of two inhibitors of protein kinase C, staurosporine (50 micrograms/kg) or polymyxin B (24 mg/kg), were administered to rabbits subjected to 30 min regional myocardial ischemia followed by 180 min reperfusion. Half of the rabbits were preconditioned while the other half served as nonpreconditioned controls. Nonpreconditioned hearts without drug or treated with staurosporine or polymyxin B resulted in 37.8 +/- 3.1, 40.5 +/- 2.8, and 42.0 +/- 7.0% infarction of the risk zone, respectively. Preconditioning limited infarct size to 7.3 +/- 2.7%. Both inhibitors blocked protection in preconditioned hearts with 36.2 +/- 2.7 and 40.9 +/- 2.5% of the risk zone infarcted, respectively. Activation of protein kinase C with 4 beta-phorbol 12-myristate 13-acetate (PMA) or with 1-oleyl-2-acetyl glycerol (OAG) mimicked preconditioning in buffer-perfused hearts. PMA (0.01 nmol/min) or OAG (10 nmol/min) for 5 min was followed by 10 min of washout. Infarct size after 30 min regional ischemia was limited in the PMA and OAG groups (6.4 +/- 1.4 and 11.7 +/- 3.3 vs. 28.0 +/- 4.5% in untreated controls) and was equipotent with ischemic preconditioning (11.8 +/- 2.2%). Polymyxin B also blocked protection from ischemic preconditioning in the isolated heart (33.0 +/- 5.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

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				T. Sato, B. O'Rourke, and E. Marban Modulation of Mitochondrial ATP-Dependent K+ Channels by Protein Kinase C Circ. Res., July 13, 1998; 83(1): 110 - 114. [Abstract] [Full Text] [PDF]

				M. Miyamae, M. M. Rodriguez, S. A. Camacho, I. Diamond, D. Mochly-Rosen, and V. M. Figueredo Activation of varepsilon  protein kinase C correlates with a cardioprotective effect of regular ethanol consumption PNAS, July 7, 1998; 95(14): 8262 - 8267. [Abstract] [Full Text] [PDF]

				M. Arai, S. Minatoguchi, G. Takemura, Y. Uno, T. Kariya, H. Takatsu, T. Fujiwara, M. Higashioka, Y. Yoshikuni, and H. Fujiwara N-Methyl-1-Deoxynojirimycin (MOR-14), an {alpha}-Glucosidase Inhibitor, Markedly Reduced Infarct Size in Rabbit Hearts Circulation, April 7, 1998; 97(13): 1290 - 1297. [Abstract] [Full Text] [PDF]

				R. J. Domenech, P. Macho, D. Velez, G. Sanchez, X. Liu, and N. Dhalla Tachycardia Preconditions Infarct Size in Dogs : Role of Adenosine and Protein Kinase C Circulation, March 3, 1998; 97(8): 786 - 794. [Abstract] [Full Text] [PDF]

				J. E. J. Schultz, A. K. Hsu, H. Nagase, and G. J. Gross TAN-67, a delta 1-opioid receptor agonist, reduces infarct size via activation of Gi/o proteins and KATP channels Am J Physiol Heart Circ Physiol, March 1, 1998; 274(3): H909 - H914. [Abstract] [Full Text] [PDF]

				A. Gysembergh, H. Margonari, J. Loufoua, A. Ovize, X. Andre-Fouet, Y. Minaire, and M. Ovize Stretch-induced protection shares a common mechanism with ischemic preconditioning in rabbit heart Am J Physiol Heart Circ Physiol, March 1, 1998; 274(3): H955 - H964. [Abstract] [Full Text] [PDF]

				H. Yokoshiki, M. Sunagawa, T. Seki, and N. Sperelakis ATP-sensitive K+ channels in pancreatic, cardiac, and vascular smooth muscle cells Am J Physiol Cell Physiol, January 1, 1998; 274(1): C25 - C37. [Abstract] [Full Text] [PDF]

				F. Tomai, F. Crea, A. Gaspardone, F. Versaci, A. S. Ghini, R. De Paulis, L. Chiariello, and P. A. Gioffre Phentolamine Prevents Adaptation to Ischemia During Coronary Angioplasty : Role of {alpha}-Adrenergic Receptors in Ischemic Preconditioning Circulation, October 7, 1997; 96(7): 2171 - 2177. [Abstract] [Full Text]

				P. Ping, J. Zhang, Y. Qiu, X.-L. Tang, S. Manchikalapudi, X. Cao, and R. Bolli Ischemic Preconditioning Induces Selective Translocation of Protein Kinase C Isoforms {epsilon} and {eta} in the Heart of Conscious Rabbits Without Subcellular Redistribution of Total Protein Kinase C Activity Circ. Res., September 19, 1997; 81(3): 404 - 414. [Abstract] [Full Text]

				K. Przyklenk, K. Hata, and R. A. Kloner Is Calcium a Mediator of Infarct Size Reduction With Preconditioning in Canine Myocardium? Circulation, August 19, 1997; 96(4): 1305 - 1312. [Abstract] [Full Text]

				M. V. Cohen, J. D. Thornton, C. S. Thornton, H. Sato, T. Miki, and J. M. Downey INTRAVENOUS CO-INFUSION OF ADENOSINE AND NOREPINEPHRINE PRECONDITIONS THE HEART WITHOUT ADVERSE HEMODYNAMIC EFFECTS J. Thorac. Cardiovasc. Surg., August 1, 1997; 114(2): 236 - 242. [Abstract] [Full Text]

				R. Nawada, T. Murakami, T. Iwase, K. Nagai, Y. Morita, I. Kouchi, M. Akao, and S. Sasayama Inhibition of Sarcolemmal Na+,K+-ATPase Activity Reduces the Infarct Size–Limiting Effect of Preconditioning in Rabbit Hearts Circulation, July 15, 1997; 96(2): 599 - 604. [Abstract] [Full Text]

				H. Miyawaki and M. Ashraf Ca2+ as a Mediator of Ischemic Preconditioning Circ. Res., June 19, 1997; 80(6): 790 - 799. [Abstract] [Full Text]

				I. Tritto, D. D'Andrea, N. Eramo, A. Scognamiglio, C. De Simone, A. Violante, A. Esposito, M. Chiariello, and G. Ambrosio Oxygen Radicals Can Induce Preconditioning in Rabbit Hearts Circ. Res., May 19, 1997; 80(5): 743 - 748. [Abstract] [Full Text]

				M. V. Cohen, Y. Liu, G. S. Liu, P. Wang, C. Weinbrenner, G. A. Cordis, D. K. Das, and J. M. Downey Phospholipase D Plays a Role in Ischemic Preconditioning in Rabbit Heart Circulation, October 1, 1996; 94(7): 1713 - 1718. [Abstract] [Full Text]

				D. R. Meldrum, J. C. Cleveland Jr., B. C. Sheridan, R. T. Rowland, A. Banerjee, and A. H. Harken CARDIAC PRECONDITIONING WITH CALCIUM: CLINICALLY ACCESSIBLE MYOCARDIAL PROTECTION J. Thorac. Cardiovasc. Surg., September 1, 1996; 112(3): 778 - 786. [Abstract] [Full Text]

				P. E. Light, A. A. Sabir, B. G. Allen, M. P. Walsh, and R. J. French Protein Kinase C–Induced Changes in the Stoichiometry of ATP Binding Activate Cardiac ATP-Sensitive K+ Channels: A Possible Mechanistic Link to Ischemic Preconditioning Circ. Res., September 1, 1996; 79(3): 399 - 406. [Abstract] [Full Text]

				C. Vahlhaus, R. Schulz, H. Post, R. Onallah, and G. Heusch No Prevention of Ischemic Preconditioning by the Protein Kinase C Inhibitor Staurosporine in Swine Circ. Res., September 1, 1996; 79(3): 407 - 414. [Abstract] [Full Text]

				T. Mizumura, J. A. Auchampach, J. Linden, R. F. Bruns, and G. J. Gross PD 81,723, an Allosteric Enhancer of the A1 Adenosine Receptor, Lowers the Threshold for Ischemic Preconditioning in Dogs Circ. Res., September 1, 1996; 79(3): 415 - 423. [Abstract] [Full Text]

				M. A. Bogoyevitch, J. Gillespie-Brown, A. J. Ketterman, S. J. Fuller, R. Ben-Levy, A. Ashworth, C. J. Marshall, and P. H. Sugden Stimulation of the Stress-Activated Mitogen-Activated Protein Kinase Subfamilies in Perfused Heart: p38/RK Mitogen-Activated Protein Kinases and c-Jun N-Terminal Kinases Are Activated by Ischemia/Reperfusion Circ. Res., August 1, 1996; 79(2): 162 - 173. [Abstract] [Full Text]

				H. Miyawaki, X. Zhou, and M. Ashraf Calcium Preconditioning Elicits Strong Protection Against Ischemic Injury via Protein Kinase C Signaling Pathway Circ. Res., July 1, 1996; 79(1): 137 - 146. [Abstract] [Full Text]