Shortening of action potential duration is not prerequisite for cardiac protection by ischemic preconditioning or a KATP channel opener.
Our purpose was to determine whether amelioration of myocardial contractile dysfunction by an ATP-sensitive potassium (KATP) channel opener or ischemic preconditioning is mediated by shortening of action potential duration during the early period of ischemia. Extracellular potassium concentration ([K+]e), monophasic action potential duration (MAPD) and thickening fraction were measured during ischemia and reperfusion of the left anterior descending coronary artery in anesthetized dogs. Control dogs were subjected to a 10-min occlusion (test occlusion) followed by a 120-min reperfusion. The five dogs which made up the pinacidil group, received 0.03 mg/kg as an i.v. bolus and then were infused at a rate of 0.04 mg/kg/h for 20 min prior to the test occlusion. In the preconditioning group, six dogs were subjected to a 5-min occlusion and a 10-min reperfusion prior to the test occlusion and reperfusion. Both pinacidil and preconditioning improved regional contraction during reperfusion after the test occlusion. In the control group, MAPD shortened and [K+]e increased during ischemia. Preconditioning abolished MAPD shortening and blunted the rise of [K+]e during ischemia. Pinacidil did not affect either the shortening of MAPD or [K+]e elevation during ischemia. These results suggest that the shortening of MAPD is not a prerequisite for amelioration of contractile dysfunction by a KATP channel opener or ischemic preconditioning.
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
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Hamada
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Yamazaki
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T
Nagao
D000200:Action Potentials / Q000502:physiology*; D000255:Adenosine Triphosphate; D000818:Animals; D003326:Coronary Circulation; D004285:Dogs; D005110:Extracellular Space; D005260:Female; D006321:Heart; D006439:Hemodynamics; D006863:Hydrogen-Ion Concentration; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D020110:Pinacidil / Q000494:pharmacology; D011188:Potassium; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D015221:Potassium Channels; D020110:Pinacidil; D000255:Adenosine Triphosphate; D011188:Potassium