Decreased endothelium-dependent vascular relaxation following subtotal coronary artery occlusion in dogs

Total coronary artery occlusion followed by reperfusion leads to neutrophil accumulation in the reperfused myocardium and a reduction in endothelium-dependent coronary artery relaxation. Attenuated coronary artery relaxation in the affected regions is thought to be related to breakdown of endothelium-derived relaxing factor (EDRF) by free oxygen radicals released during reperfusion. To determine if temporary subtotal coronary artery narrowing leads to similar alteration in vascular reactivity, eight open-chest dogs were subjected to 1 h of left anterior descending (LAD) coronary artery narrowing (70% reduction in basal flow) and pacing-induced increase in heart rate (30% above baseline) followed by reperfusion for 1 h. Thereafter reactivity of ischemic-reperfused LAD and nonischemic circumflex (Cx) coronary artery rings to the thromboxane A2 analog U46,619 and EDRF-dependent vasorelaxants acetylcholine (ACh), thrombin, and adenosine diphosphate (ADP), as well as to EDRF-independent vasorelaxant nitroglycerin (NTG), was examined. Unlike in the setting of total coronary artery occlusion, reperfused myocardium or LAD did not reveal neutrophil infiltration. However, contraction in response to U46,619 was markedly (P < .001) increased in the LAD rings compared to that in the Cx rings. ACh-induced relaxation was only modestly decreased (P < .05) in the LAD coronary artery rings, but the relaxation in response to both thrombin and ADP was markedly diminished (P < .01) as compared to that in the Cx rings. Coronary artery ring relaxation in response to NTG was preserved in the LAD rings. Pretreatment of coronary artery rings with indomethacin did not alter the enhanced contraction or diminished endothelium-dependent relaxation of LAD coronary artery rings.(ABSTRACT TRUNCATED AT 250 WORDS)