DEFECTIVE ENDOTHELIUM-MEDIATED CONTROL OF CORONARY CIRCULATION IN CONSCIOUS DOGS AFTER HEART-FAILURE

The goal of this study was to determine whether coronary endothelial f unction was altered after pacing-induced heart failure in conscious do gs. Fourteen mongrel dogs were chronically instrumented for measuremen ts of systemic hemodynamics, left circumflex coronary artery diameter (CD) and blood flow, and for left ventricular pacing for 4 wk. Heart f ailure developed during this pacing regimen and was characterized by a significant reduction in arterial pressure, an increase in left atria l pressure, a resting tachycardia, a depression of left ventricular dP /dt to isoproterenol injection, a significant reduction of the slope o f the end-systolic pressure-diameter relationship, and all of the char acteristic clinical signs. During heart failure, the dilation of CD af ter release of a brief coronary artery occlusion, acetylcholine, and a rachidonic acid was attenuated, whereas prostaglandin (PG) I-2- and ni troglycerin-induced dilations of CD were unchanged. The coronary blood flow responses to occlusion, acetylcholine, and nitroglycerin were de pressed, but not to PG. Large coronary arteries and microvessels were isolated from normal and failing hearts. Both isolated large coronary arteries and microvessels from failing hearts produced significantly l ess nitrite, the immediate metabolite of nitric oxide in aqueous solut ion, than those of normal hearts. Thus endothelium-mediated control of the coronary circulation was depressed during heart failure. A decrea se in the production of nitric oxide-endothelium-derived relaxing fact or was most likely responsible for this depression.