Adenosine triphosphate-sensitive K+ channels mediate postcardioplegia coronary hyperemia.
The purpose of the present study was to examine the role of adenosine triphosphate-sensitive potassium channels in mediating the coronary hyperemic response after crystalloid cardioplegia. Thirteen pigs were placed on normothermic cardiopulmonary bypass support. Hearts were arrested with cold (4 degrees C) crystalloid ([K+] 25 mmol/L) cardioplegic solution for 60 minutes. In seven of these pigs, hearts were then reperfused for 60 minutes with warm blood, and the animal was separated from cardiopulmonary bypass. The in vivo responses to the intracoronary administration of the K+ adenosine triphosphate channel blocker glibenclamide (50 gm/kg per minute) or the K+ adenosine triphosphate channel opener pinacidil (2 gm/kg per minute) were evaluated before cardiopulmonary bypass (baseline) and after 2 minutes and 60 minutes of reperfusion in the cardioplegia-reperfusion group. Under baseline conditions, glibenclamide and pinacidil induced a respective decrease and increase in coronary blood flow and an increase and a decrease in coronary vascular resistance. Coronary responses to glibenclamide and pinacidil were markedly enhanced after 2 minutes or 60 minutes of postcardioplegia reperfusion. In vitro responses of coronary arterioles (90 to 180 microns) were examined in a pressurized, no-flow state with video microscopy. The contractile response of coronary arterioles to glibenclamide and the relaxation response to pinacidil were significantly enhanced 2 minutes or 60 minutes after reperfusion (all p < 0.05 versus control). The response to pinacidil was markedly inhibited by glibenclamide, which confirms these antagonistic effects on K+ adenosine triphosphate channels. Decreased tissue concentrations of adenosine triphosphate in the coronary arterial smooth muscle and myocardium were observed after cardioplegia and persisted for up to 60 minutes of reperfusion (both p < 0.05 versus control). These results suggest that coronary hyperemia associated with postischemic cardioplegia is mediated in part by activation of K+ adenosine triphosphate channels in the coronary microcirculation.
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000378:metabolism / Q000503:physiopathology; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006324:Heart Arrest, Induced / Q000009:adverse effects; D006940:Hyperemia / Q000209:etiology / Q000503:physiopathology*; D066298:In Vitro Techniques; D018715:Microscopy, Video; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D020110:Pinacidil; D015221:Potassium Channels / Q000502:physiology*; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D006146:Guanidines; D015221:Potassium Channels; D014665:Vasodilator Agents; D009599:Nitroprusside; D020110:Pinacidil; D000255:Adenosine Triphosphate; D005905:Glyburide