Involvement of activation of ATP-dependent potassium channels in ischemic preconditioning in swine.
This study evaluated the importance of ATP-dependent potassium channels (KATP) for ischemic preconditioning (IP) in swine. Swine were studied because due to the sparsity of their innate collateral circulation infarct size (IS) development closely resembles that observed in humans. Ninety minutes of ischemia at a blood flow reduction sufficient to reduce regional myocardial work by 90% caused 13.2 +/- 8.9% (SD) IS of the area at risk. A single cycle of 10-min preconditioning ischemia followed by 15-min reperfusion reduced IS after 90 min of ischemia to 2.8 +/- 2.7%. The epicardial monophasic action potential duration at 50% repolarization (MAP50) was decreased more markedly during the initial 10 min of the prolonged ischemia than during the first 10 min of the preconditioning ischemic period (84 +/- 4 vs. 89 +/- 2%). Transmural myocardial adenosine (ADO) uptake was reversed to net release during both ischemic periods and during the initial phase of reperfusion. Glibenclamide (0.5 mg/kg, followed by 50 micrograms/min i.v.) abolished the reduction in MAP50 without altering ADO release. Glibenclamide did not alter IS per se (13.0 +/- 7.6%) but abolished the beneficial effect of IP (IS: 13.6 +/- 6.2%). Thus blockade of KATP with glibenclamide abolishes the IS-reducing effect of IP in swine but does not reduce ADO release.
Schulz
R
R
Abteilung für Pathophysiologie, Zentrum für Innere Medizin des Universitätsklinikums Essen, Germany.
Rose
J
J
Heusch
G
G
D000200:Action Potentials; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000502:physiology / Q000503:physiopathology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006339:Heart Rate; D006801:Humans; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D012044:Regression Analysis; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D016277:Ventricular Function, Left
D001786:Blood Glucose; D015221:Potassium Channels; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D006003:Glycogen; D005905:Glyburide