Endothelium-dependent Coronary Response is Impaired in the Myocardium at an Early Phase of Post-infarct Remodeling.

Abstract

The aim of the present study was to characterize endothelium-dependent and -independent coronary functions in remodeling hearts after infarction. First, echocardiography showed that the left ventricular diastolic dimension and thickness of the non-ischemic region were increased by 25% and 20%, respectively, at 2 weeks after coronary ligation in the rabbit heart. In the second series of experiments, 2 weeks after coronary ligation or a sham operation, the heart was isolated and perfused with modified Krebs-Henseleit buffer at 75 mmHg, and effluent from the pulmonary artery was measured as total coronary flow (CF). Regional CF analysis by microspheres indicated that flow to the infarcted region as a percentage of total CF is negligibly small. There was no significant difference between CF responses to sodium nitroprusside (10(-9)-10(-5) mole/l) in the sham-operated and remodeling hearts. However, the increase in CF after acetylcholine (ACh: 10(-8)-10(-5) mole/l) injection was significantly reduced by approximately 50% in the remodeling hearts compared to that in the sham-operated hearts. Furthermore, the percent increase in CF by ACh (10(-5) mole/l) was inversely correlated with weight of the remodeling myocardium (r = -0.630, p < 0.05). These results suggest that endothelium-dependent vasodilatory function is impaired in the myocardium at the early stage of post-infarct remodeling and that this endothelial dysfunction is closely related to the degree of hypertrophy of the remodeling myocardium.