Impaired canine coronary vasodilator response to acetylcholine and bradykinin after occlusion-reperfusion.

Abstract

Previous studies indicate impairment of coronary arterial ring relaxation in response to acetylcholine (ACh) following coronary reperfusion, mediated via loss of endothelium-derived relaxing factor (EDRF). To examine if coronary vasodilator reserve is reduced following coronary ocdusionreperfusion in intact animnk, 16 open-chest mongrel dogs were subjected to 1 hour of total left circumflex (Cx) coronary artery ocduskm followed by reperfusion for 1 hour. Prior to Cx occlusion, coronary blood flow increased and vascular resistance decreased (both p<0.01) in response to ACh and bradykinin (BK). Following reperfusion, increase in Cx coronary flow in response to both vasodilators was significantly (p^O.Ol) unpaired. Myocardial histology showed extensive neutrophil infiltration and capillary plugging by neutrophils in the Cx compared with the left anterior descending coronary artery-supplied myocardium. Myocardial myeloperoxidase activity was also increased in the Cx compared with the left anterior descending region (p<0.02). Pretreatment of four dogs with indomethadn partially reduced the vasodilator response to BK but not to ACh. However, indomethadn did not affect reperfusion-induced attenuation of BK or ACh's coronary vasodilator effects. To determine if calcium blocker verapamil would modify reperfusion-induced impairment in coronary vasodilator reserve, six dogs were treated with verapamil. Although verapamfl enhanced coronary vasodilator effects of ACh and BK, it did not modify reperfusioninduced attenuation of coronary vasodilator reserve. Myocardial neutrophil accumulation and myeloperoxidase activity was also similar in control, indomethadn, and verapamil-treated dogs. These observations suggest that coronary reperfusion impairs coronary vasodilator reserve in intact dogs. This impairment is not modified by prostaglandin inhibition or by caldum blockade. Received February 22, 1988; accepted June 15, 1988. relaxation evoked by acetylcholine (ACh). Subsequent studies showed that the coronary artery ring relaxation by thrombin is converted to constriction when dog coronary arteries are subjected to total occlusion followed by reperfusion. 5 VanBenthuysen et al 6 have also shown attenuation of ACh-induced relaxation of coronary arterial rings from dogs subjected to temporary coronary occlusion. In those studies, electron microscopy demonstrated focal areas of endothelial cell injury with partial detachment of the cells from the underlying subendothelium.Recent studies have shown extensive capillary plugging by neutrophils in the myocardium of dogs following coronary occlusion and reperfusion, 78 which may relate to the microvascular origin of the "no-reflow" phenomenon. 9 Neutrophil capillary plugging reduces the cross-sectional area of the microvascular bed and could reduce coronary vasodilator reserve. Bradykinin (BK) dilates coronary arteries in a dose-dependent manner by stimulating release of EDRF as well as another potent vasodilator from the vessel wall, prostacyclin (PGI2).10 " Pretreatment of t...

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