HEMODYNAMIC VASCULAR FORCES CONTRIBUTE TO IMPAIRED ENDOTHELIUM-DEPENDENT VASODILATION IN REPERFUSED CANINE EPICARDIAL CORONARY-ARTERIES

Objectives. We studied canine coronary arterial vasoreactivity after o cclusion and reperfusion to examine whether reduced flow or pressure c ontributed to the abnormalities observed. Background. Ischemia and rep erfusion alter endothelial and myocardial function. Causative factors may include altered flow complement activation or free radical product ion by endothelial or white blood cells after reoxygenation and neutro phil activation. Methods. The coronary arteries of anesthetized, open chest dogs were subjected to 90-min occlusion +/-2 h of reperfusion. T he effect of reperfusion on arterial responses to intracoronary acetyl choline, nitroprusside and phenylephrine was studied using in vivo ult rasound. Arterial segments were also harvested, perfused ex vivo with cell-free buffer and exposed to potassium chloride, nitroprusside, ace tylcholine and bradykinin. The effect of ex vivo flow cessation with o r without maintained intralumen pressure was also studied. Results. Re sults are expressed as mean value +/- SEM. In vivo arterial cross-sect ional area increased during infusion with acetylcholine (10(-5) mol/li ter [18.5 +/- 9%]) and nitroprusside (10(-5) mol/liter [22.5 +/- 10%]) and decreased with phenylephrine (10(-5) mol/liter [7.6 +/- 7%]). Aft er reperfusion, acetylcholine caused 13.5 +/- 9% vasoconstriction. Nit roprusside and phenylephrine responses were unchanged. Reperfused arte rial segments also showed impaired vasodilation in response to 10(-6) mol/liter of acetylcholine (10.6 +/- 5.1% vs. 47.1 +/- 4.9% in control vessels) and 10(-8) mol/liter of bradykinin (4.4 +/- 6.7% vs. 27.9 +/ - 8% in control vessels). Ex vivo flow cessation impaired acetylcholin e-mediated vasodilation, but this abnormality was prevented when high intralumen pressure was maintained during the no-flow period. Conclusi ons. Reduction in how and intralumen pressure contribute to the impair ed acetylcholine mediated vasodilation seen after coronary occlusion. This is prevented by maintaining high intralumen pressure during the n o-flow period, suggesting that hemodynamic forces may change endotheli al function independent of circulating complement or blood cell elemen ts.