MICROVASCULAR DYSFUNCTION AFTER MYOCARDIAL-ISCHEMIA

Endothelium-mediated relaxation and smooth muscle function in large co ronary arteries are resistant to prolonged global ischemia. We used a small-vessel myograph to test the hypothesis that small intramyocardia l artery endothelium and smooth muscle function have greater sensitivi ty to ischemic injury than large artery endothelium and smooth muscle. Normothermic global ischemia was induced in 15 porcine hearts, Intram yocardial arterial ring segments were assessed at 0, 30, 60, 90, and 1 20 minutes of ischemia in vitro with a small-vessel myograph. Potassiu m determined smooth muscle contraction, bradykinin endothelium-mediate d relaxation, and sodium nitroprusside direct smooth muscle relaxation . Endothelium-mediated relaxation after 30 minutes of ischemia was sim ilar to control (56% versus 66%) but was impaired at 60, 90, and 120 m inutes of ischemia (32%, 11%, and 6%). Smooth muscle contraction was u nchanged at 30 and 60 minutes compared with control (56 and 53 versus 63 mm Hg) but was significantly decreased at 90 and 120 minutes (33 an d 13 mm Hg). Direct smooth muscle relaxation was significantly decreas ed at 120 minutes of ischemia compared with control (58% versus 95%). In a previous study, epicardial coronary artery endothelium-mediated s mooth muscle vasodilation and direct smooth muscle vasodilation were p reserved until 160 minutes of ischemia. After 160 minutes of ischemia, endothelium-mediated relaxation was lost and only direct smooth muscl e vasodilation was preserved. In contrast to vasodilation, vasoconstri ction was significantly reduced at 140 minutes of ischemia. These data indicate a greater and earlier adverse effect of ischemia on intramyo cardial arterial endothelium-mediated relaxation than smooth muscle co ntraction or relaxation. These data support the hypothesis that there is an early functional endothelial cell injury associated with global ischemia. Relaxation that is endothelium-dependant in intramyocardial arteries is more sensitive to ischemic injury than in epicardial arter ies. Unique to this study was the evaluation of small intramyocardial arteries (281 + 29 mu m) that are the primary sites of coronary vascul ar resistance. Microvascular endothelial dysfunction after ischemia, t herefore, may contribute to the ''no-reflow phenomenon'' seen during r eperfusion injury.