Acute impairment of endothelium-dependent relaxations to aggregating platelets following reperfusion injury in canine coronary arteries.

Experiments were designed to determine whether endothelial injury contributes to augmented coronary vascular tone seen during myocardial reperfusion. Canine left anterior descending coronary arteries were exposed to ischemia followed by reperfusion (60 minutes each). Rings (3-4 mm) of the reperfused artery and of normal left circumflex (control) coronary artery segments were prepared. Rings were suspended for isometric force measurement in organ chambers containing modified Krebs' Ringer bicarbonate solution (37 degrees C, 95% O2-5% CO2). Endothelium-independent contractions to KCl and prostaglandin F2 alpha were unaltered after reperfusion. Endothelium-dependent relaxations to nitric oxide, sodium nitroprusside, and isoproterenol were comparable in control and reperfused arteries. However, reperfused coronary arteries contracted with prostaglandin F2 alpha lost the ability to express endothelium-dependent relaxations to aggregating platelets. Reperfused arterial rings also exhibited impaired endothelium-dependent relaxations to acetylcholine, the calcium ionophore A23187, and the platelet-derived compounds ADP and serotonin. Quiescent (noncontracted) reperfused arterial rings exhibited larger contractions than controls when exposed to aggregating platelets. In such quiescent rings, the endothelium-dependent increase in tension to hemoglobin was unaltered after reperfusion. Thus, coronary reperfusion impairs the normal endothelium-dependent relaxations to aggregating platelets and vasoactive drugs. This impairment of platelet-mediated coronary relaxation could help explain the increased vascular tone and tendency toward vasospasm commonly observed after reperfusion of the coronary arteries.