Cardioprotective actions of potassium channel openers.
The potential cardioprotective effect of two pure potassium channel openers, bimakalim (EMD 52692) and aprikalim (RP 52891), on myocardial ischaemia/reperfusion injury was investigated in barbital-anaesthetized dogs. In a model of reversible ischaemia/reperfusion injury, administration of bimakalim as an intravenous bolus prior to ischaemia or administration of a non-hypotensive dose of aprikalim as a constant intravenous infusion resulted in a reduction in reperfusion contractile dysfunction (myocardial 'stunning') produced by a single 15-min coronary artery occlusion. Administration of aprikalim only during the reperfusion period had no beneficial effect. Similarly, in a model of irreversible ischaemia/reperfusion injury (90 min of coronary artery occlusion followed by 5 h of reperfusion), intravenous infusion of bimakalim at a dose which reduced aortic blood pressure approximately 15-20 mmHg or infusion of aprikalim at a non-hypotensive dose throughout the entire experiment produced a significant reduction in myocardial infarct size. A protective effect of bimakalim was not observed when it was administered during the reperfusion period only. In both the stunned myocardium model as well as the infarcted myocardium model, the beneficial effects of the potassium channel openers could not be attributed to differences in the traditional determinants of the extent of ischaemia/reperfusion injury; area at risk size, oxygen consumption, or collateral blood flow. Furthermore, the anti-ischaemic actions of the potassium channel openers were blocked by pre-treatment with the ATP-dependent potassium (KATP) channel antagonist, glibenclamide.(ABSTRACT TRUNCATED AT 250 WORDS)
Auchampach
J A
JA
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Maruyama
M
M
Gross
G J
GJ
D000818:Animals; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004095:Dihydropyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D017682:Myocardial Stunning / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D010847:Picolines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects*; D011714:Pyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001578:Benzopyrans; D004095:Dihydropyridines; D010847:Picolines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011714:Pyrans; D014665:Vasodilator Agents; C061043:aprikalim; C061050:bimakalim; D005905:Glyburide