AJP - Heart and Circulatory Physiology, Vol 272, Issue 1 334-H342, Copyright © 1997 by American Physiological Society

ARTICLES

KATP channels and memory of ischemic preconditioning in dogs: synergism between adenosine and KATP channels

Z. Yao, T. Mizumura, D. A. Mei and G. J. Gross
Department of Anesthesia, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.

Results from numerous studies have shown that there is an important link between adenosine A1 receptors and ATP-sensitive potassium (KATP) channels in mediating the cardioprotective effects of ischemic preconditioning (PC). The major aim of the present study was to determine whether occupation of A1 receptors and/or the opening of KATP channels is involved in the time delay between the PC stimulus and the prolonged ischemic insult or the "memory" of PC to reduce infarct size. Barbital sodium-anesthetized dogs were subjected to 1 h of left anterior descending coronary artery (LAD) occlusion followed by 4 h of reperfusion. Ischemic PC was elicited by 10 min of LAD occlusion followed by 1 h of reperfusion (1-h memory) before the 1-h occlusion period. Either adenosine (800 g/min), bimakalim (3 g/min), a combination of two lower doses of each agent (400 g/min of adenosine and 0.3 g/min of bimakalim), or an equivalent volume of saline was infused into the LAD for 10 min followed by a 1-h drug-free period before the 1-h ischemic insult. In another series, glibenclamide, 8-cyclopentyl-1,3-dipropylxanthine (a selective A1-receptor blocker), or PD-115199 (a nonselective adenosine-receptor antagonist) was administered 50 min after ischemic PC (10 min before the 1-h occlusion period). Infarct size (IS) was expressed as a percentage of the area at risk. PC with 1 h of reperfusion resulted in a marked reduction in IS (8.1 +/- 6.5 vs. 29.8 +/- 5.8% in control dogs). Administration of adenosine or bimakalim followed by a 1-h drug-free period had no effect on IS; however, the simultaneous administration of adenosine and bimakalim resulted in a marked decrease in IS (11.5 +/- 2.7%). One hour after ischemic PC, administration of glibenclamide blocked the protective effect of ischemic PC, whereas 8-cyclopentyl-1,3-dipropylxanthine or PD-115199 did not affect it. These results provide evidence that the opening of myocardial KATP channels may play an important role in the memory of ischemic PC in the canine heart and also suggest that adenosine and the KATP channel may have a synergistic interaction that is important for the memory phase of PC.

This article has been cited by other articles:

				T. Okada, H. Otani, Y. Wu, T. Uchiyama, S. Kyoi, R. Hattori, T. Sumida, H. Fujiwara, and H. Imamura Integrated pharmacological preconditioning and memory of cardioprotection: role of protein kinase C and phosphatidylinositol 3-kinase Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H761 - H767. [Abstract] [Full Text] [PDF]

				S. B. Kristiansen, O. Henning, R. K. Kharbanda, J. E. Nielsen-Kudsk, M. R. Schmidt, A. N. Redington, T. T. Nielsen, and H. E. Botker Remote preconditioning reduces ischemic injury in the explanted heart by a KATP channel-dependent mechanism Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1252 - H1256. [Abstract] [Full Text] [PDF]

				L. Xiong, Y. Zheng, M. Wu, L. Hou, Z. Zhu, X. Zhang, and Z. Lu Preconditioning with Isoflurane Produces Dose-Dependent Neuroprotection via Activation of Adenosine Triphosphate-Regulated Potassium Channels After Focal Cerebral Ischemia in Rats Anesth. Analg., January 1, 2003; 96(1): 233 - 237. [Abstract] [Full Text] [PDF]

				Y. Ohnuma, T. Miura, T. Miki, M. Tanno, A. Kuno, A. Tsuchida, and K. Shimamoto Opening of mitochondrial KATP channel occurs downstream of PKC-epsilon activation in the mechanism of preconditioning Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H440 - H447. [Abstract] [Full Text] [PDF]

				J. Mullenheim, A. Molojavyi, B. Preckel, V. Thamer, and W. Schlack Thiopentone does not block ischemic preconditioning in the isolated rat heart : [Le thiopental n'entrave pas le preconditionnement ischemique dans le coeur de rat isole] Can J Anesth, September 1, 2001; 48(8): 784 - 789. [Abstract] [Full Text] [PDF]

				S. Wang, J. Cone, and Y. Liu Dual roles of mitochondrial KATP channels in diazoxide-mediated protection in isolated rabbit hearts Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H246 - H255. [Abstract] [Full Text] [PDF]

				S. L. Hale and R. A. Kloner Effect of combined KATP channel activation and Na+/H+ exchange inhibition on infarct size in rabbits Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2673 - H2677. [Abstract] [Full Text] [PDF]

				H. Takano, X.-L. Tang, and R. Bolli Differential role of KATP channels in late preconditioning against myocardial stunning and infarction in rabbits Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2350 - H2359. [Abstract] [Full Text] [PDF]

				W. Tang, M. H. Weil, S. Sun, A. Pernat, and E. Mason KATP channel activation reduces the severity of postresuscitation myocardial dysfunction Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1609 - H1615. [Abstract] [Full Text] [PDF]

				G. J. Gross and R. M. Fryer Mitochondrial KATP Channels : Triggers or Distal Effectors of Ischemic or Pharmacological Preconditioning? Circ. Res., September 15, 2000; 87(6): 431 - 433. [Full Text] [PDF]

				T. Pain, X.-M. Yang, S. D. Critz, Y. Yue, A. Nakano, G. S. Liu, G. Heusch, M. V. Cohen, and J. M. Downey Opening of Mitochondrial KATP Channels Triggers the Preconditioned State by Generating Free Radicals Circ. Res., September 15, 2000; 87(6): 460 - 466. [Abstract] [Full Text] [PDF]

				V. H. Thourani, R. S. Ronson, J. E. Jordan, R. A. Guyton, and J. Vinten-Johansen Adenosine A3 pretreatment before cardioplegic arrest attenuates postischemic cardiac dysfunction Ann. Thorac. Surg., June 1, 1999; 67(6): 1732 - 1737. [Abstract] [Full Text] [PDF]

				G. J. Gross and R. M. Fryer Sarcolemmal Versus Mitochondrial ATP-Sensitive K+ Channels and Myocardial Preconditioning Circ. Res., May 14, 1999; 84(9): 973 - 979. [Abstract] [Full Text] [PDF]

				J. E. Baker, P. Holman, and G. J. Gross Preconditioning in Immature Rabbit Hearts : Role of KATP Channels Circulation, March 9, 1999; 99(9): 1249 - 1254. [Abstract] [Full Text] [PDF]

				M. Pek-Scott and P. L. Lutz ATP-sensitive K+ channel activation provides transient protection to the anoxic turtle brain Am J Physiol Regulatory Integrative Comp Physiol, December 1, 1998; 275(6): R2023 - R2027. [Abstract] [Full Text] [PDF]

				Y. Liu, T. Sato, B. O'Rourke, and E. Marban Mitochondrial ATP-Dependent Potassium Channels : Novel Effectors of Cardioprotection? Circulation, June 23, 1998; 97(24): 2463 - 2469. [Abstract] [Full Text] [PDF]

				E. Giannella, H.-C. Mochmann, and R. Levi Ischemic Preconditioning Prevents the Impairment of Hypoxic Coronary Vasodilatation Caused by Ischemia/Reperfusion : Role of Adenosine A1/A3 and Bradykinin B2 Receptor Activation Circ. Res., September 19, 1997; 81(3): 415 - 422. [Abstract] [Full Text]