ENDOTHELIUM-DEPENDENT DILATION OF THE CORONARY MICROVASCULATURE IS IMPAIRED IN DILATED CARDIOMYOPATHY

Dilator reserve of the coronary microvasculature is diminished in patients with dilated cardiomyopathy. Although increased extravascular compressive forces, tachycardia, and increased myocardial mass can explain some impairment, recent evidence suggests the possibility of intrinsic microvascular disease. We tested the hypothesis that impairment of endothelium-dependent dilation of the microvasculature could be a contributing mechanism. We infused the endothelium-dependent dilator acetylcholine (Ach) (10-8 to 10-6 M) and the smooth muscle vasodilator adenosine (AD) (10-6 to 10-4 M) into the left anterior descending coronary artery in eight patients with dilated cardiomyopathy (mean ejection fraction, 28%) and seven controls (atypical chest pain). Small vessel resistance was assessed by measuring coronary blood flow (CBF) at constant arterial pressure with a Doppler velocity catheter (corrected for cross-sectional area by angiography). With Ach, control patients increased CBF 232±40% (mean±SEM), whereas CBF did not significantly change in cardiomyopathy patients (41±24%) (p<0.0001, control vs. cardiomyopathy). With AD, control patients increased CBF 422±56% and cardiomyopathy patients increased CBF 268±43% (p=0.13). An index of the proportion of coronary flow reserve attributable to endothelium-dependent vasodilation was obtained by standardizing each patient's Ach dose response to his maximal AD flow response. In seven control patients receiving both Ach and AD, 56±9% of the maximal AD flow response was attained with the endothelium-dependent vasodilator Ach, whereas in seven cardiomyopathy patients receiving both Ach and AD, only 23±14% of the maximal AD response was attained (p<0.01). Thus, endothelium-dependent vasodilator function is impaired in the coronary microvasculature of patients with dilated cardiomyopathy. There might be pathogenetic links between dysfunction of the endothelium and myocardial failure.