AJP - Heart and Circulatory Physiology, Vol 261, Issue 6 1864-H1871, Copyright © 1991 by American Physiological Society

ARTICLES

Effects of glibenclamide and nicorandil on cardiac function during ischemia and reperfusion in isolated perfused rat hearts

A. Mitani, K. Kinoshita, K. Fukamachi, M. Sakamoto, K. Kurisu, Y. Tsuruhara, F. Fukumura, A. Nakashima and K. Tokunaga
Division of Cardiovascular Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

We examined influences of a blocker (glibenclamide) and an opener (nicorandil) of the ATP-sensitive potassium (KATP) channel on extracellular K concentration [( K+]e), as well as the myocardial function and metabolites during global ischemia and reperfusion in Langendorff-perfused rat heart preparation. In control hearts, [K+]e began to rise 20 s after the onset of ischemia up to an initial peak (8.3 +/- 0.3 mM) at 2.5 +/- 0.7 min, then fell to 6.0 +/- 0.8 mM after 8.2 +/- 0.7 min, and then rose progressively to 14.6 +/- 0.8 mM at the end of 30 min of ischemia. Glibenclamide (50 microM) reduced the initial peak of [K+]e to 7.2 +/- 0.3 mM (P less than 0.01), and nicorandil (200 microM) increased it to 9.4 +/- 0.6 mM (P less than 0.01). There were no significant differences in [K+]e values among all groups at the end of ischemia. During ischemia, nicorandil decreased the time to mechanical arrest from 1.9 +/- 0.1 min to 1.5 +/- 0.1 min, whereas it was increased by glibenclamide to 2.7 +/- 0.4 min. In control hearts, the time to onset of ischemic contracture was 14.7 +/- 1.8 min. Nicorandil delayed onset of contracture and glibenclamide accelerated it. Thus we have confirmed that some part of the early increase in [K+]e during ischemia is attributable to K+ efflux through the KATP channel in our model, and opening of the KATP channel may contribute to a rapid reduction of the contractility of the ischemic myocardium that subsequently protects the myocardium against further ischemic injury.

This article has been cited by other articles:

				J. R. Terkildsen, E. J. Crampin, and N. P. Smith The balance between inactivation and activation of the Na+-K+ pump underlies the triphasic accumulation of extracellular K+ during myocardial ischemia Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H3036 - H3045. [Abstract] [Full Text] [PDF]

				T. Saito, T. Sato, T. Miki, S. Seino, and H. Nakaya Role of ATP-sensitive K+ channels in electrophysiological alterations during myocardial ischemia: a study using Kir6.2-null mice Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H352 - H357. [Abstract] [Full Text] [PDF]

				J. P. Headrick, N. S. Gauthier, R. Morrison, and G. P. Matherne Cardioprotection by KATP channels in wild-type hearts and hearts overexpressing A1-adenosine receptors Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1690 - H1697. [Abstract] [Full Text] [PDF]

				R. Sato, J. Yamazaki, and T. Nagao Temporal Differences in Actions of Calcium Channel Blockers on K+ Accumulation, Cardiac Function, and High-Energy Phosphate Levels in Ischemic Guinea Pig Hearts J. Pharmacol. Exp. Ther., May 1, 1999; 289(2): 831 - 839. [Abstract] [Full Text]

				A. W. Gomoll, R. A. Roth, R. E. Swillo, A. J. Baird, C. S. Sargent, R. W. Behling, H. J. Malone, and G. J. Grover Effect of Timing of Treatment of the Glyburide-Reversible Cardioprotective Activity of BMS-180448 J. Pharmacol. Exp. Ther., April 1, 1997; 281(1): 24 - 33. [Abstract] [Full Text]

				A. Kanda, I. Watanabe, M. L. Williams, C. L. Engle, S. Li, G. G. Koch, and L. S. Gettes Unanticipated Lessening of the Rise in Extracellular Potassium During Ischemia by Pinacidil Circulation, April 1, 1997; 95(7): 1937 - 1944. [Abstract] [Full Text]

				M. Yamashita, R. A. Schmid, S. Fujino, J. D. Cooper, and G. A. Patterson NICORANDIL, A POTENT ADENOSINE TRIPHOSPHATE-SENSITIVE POTASSIUM-CHANNEL OPENER, AMELIORATES LUNG ALLOGRAFT REPERFUSION INJURY J. Thorac. Cardiovasc. Surg., November 1, 1996; 112(5): 1307 - 1314. [Abstract] [Full Text]

				J. S. Lawton, G. C. Harrington, C. T. Allen, P.-W. Hsia, and R. J. Damiano Jr Myocardial Protection With Pinacidil Cardioplegia in the Blood-Perfused Heart Ann. Thorac. Surg., June 1, 1996; 61(6): 1680 - 1688. [Abstract] [Full Text]

				Y. Qiu, M. Galinanes, and D. J. Hearse PROTECTIVE EFFECT OF NICORANDIL AS AN ADDITIVE TO THE SOLUTION FOR CONTINUOUS WARM CARDIOPLEGIA J. Thorac. Cardiovasc. Surg., October 1, 1995; 110(4): 1063 - 1072. [Abstract] [Full Text]

				S. Sugimoto, P. E. Puddu, F. Monti, M. Schiariti, P. P. Campa, and B. Marino Pretreatment with the adenosine triphosphate-sensitive potassium channel opener nicorandil and improved myocardial protection during high-potassium cardioplegic hypoxia J. Thorac. Cardiovasc. Surg., September 1, 1994; 108(3): 455 - 466. [Abstract] [Full Text]