title: Coronary smooth muscle reactivity to muscarinic stimulation after ischemia-reperfusion in porcine myocardial infarction.
abstract: This study tested whether ischemia-reperfusion alters coronary smooth muscle reactivity to vasoconstrictor stimuli such as those elicited by an adventitial stimulation with methacholine. In vitro studies were performed to assess the reactivity of endothelium-denuded infarct-related coronary arteries to methacholine (n = 18). In addition, the vasoconstrictor effects of adventitial application of methacholine to left anterior descending (LAD) coronary artery was assessed in vivo in pigs submitted to 2 h of LAD occlusion followed by reperfusion (n = 12), LAD deendothelization (n = 11), or a sham operation (n = 6). Endothelial-dependent vasodilator capacity of infarct-related LAD was assessed by intracoronary injection of bradykinin (n = 13). In vitro, smooth muscle reactivity to methacholine was unaffected by ischemia-reperfusion. In vivo, baseline methacholine administration induced a transient and reversible drop in coronary blood flow (9.6 +/- 4.6 to 1.9 +/- 2.6 ml/min, P < 0.01), accompanied by severe left ventricular dysfunction. After ischemia-reperfusion, methacholine induced a prolonged and severe coronary blood flow drop (9.7 +/- 7.0 to 3.4 +/- 3.9 ml/min), with a significant delay in recovery (P < 0.001). Endothelial denudation mimics in part the effects of methacholine after ischemia-reperfusion, and intracoronary bradykinin confirmed the existence of endothelial dysfunction. Infarct-related epicardial coronary artery shows a delayed recovery after vasoconstrictor stimuli, because of appropriate smooth muscle reactivity and impairment of endothelial-dependent vasodilator capacity.
authors.affiliation: Laboratory of Cardiovascular Physiology, Vall d'Hebron Hospitals and Cardiology Service, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, 08025 Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez-Sinovas
authors.forename: Josep
authors.initials: J
authors.lastname: Bis
authors.forename: Inocencio
authors.initials: I
authors.lastname: Anivarro
authors.forename: Javier
authors.initials: J
authors.lastname: de la Torre
authors.forename: Antoni
authors.initials: A
authors.lastname: Bayés-Genís
authors.forename: Juan
authors.initials: J
authors.lastname: Cinca
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D003326:Coronary Circulation / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology*; D004562:Electrocardiography; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009203:Myocardial Infarction / Q000503:physiopathology*; D010496:Pericardium / Q000503:physiopathology; D015427:Reperfusion Injury / Q000503:physiopathology*; D013552:Swine; D014661:Vasoconstriction / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
chemical_list: D018721:Muscarinic Agonists; D016210:Methacholine Chloride; D001920:Bradykinin