Coronary endothelial dysfunction in humans is associated with myocardial perfusion defects

Background Coronary endothelial dysfunction may occur in patients with minimally obstructive coronary artery disease and angina, and potentially may cause myocardial ischemia. Methods and Results Coronary endothelium-dependent vasodilation was examined in patients with angina and <50% coronary artery diameter (CAD) stenosis by selectively infusing acetylcholine (10(-6) mom to 10(-4) mol/L) into the left anterior descending coronary artery (LAD). Percent change in CAD (%Delta CAD) was measured by quantitative coronary angiography, and percent change in coronary blood flow (%Delta CBF) was calculated using intracoronary flow Doppler. Coronary endothelium-independent vasodilation was examined using intracoronary adenosine and nitroglycerin. Tc-99m sestamibi was injected intravenously just prior to the infusion of the highest dose of acetylcholine: Patients were divided blindly into three groups: Perfusion defects in non-LAD territory (group 1, n=6), no perfusion defects (group 2, n=7), and perfusion defects in the LAD territory (group 3: n=7). All patients had intact endothelium-independent vasodilation. In group 1: perfusion defects outside the LAD territory reflected an increase in %Delta CAD and %Delta CBF by 24+/-5% and 241+/-46% in the LAD. In group 2, %Delta CAD decreased by 26+/-5%, but %Delta CBF increased by 54+/-17%. Tn group 3, perfusion defects were within the LAD territory, reflecting a decrease in %Delta CAD and %Delta CBF by 35+/-5% and 51+/-14%, respectively. Conclusions This study demonstrates that coronary endothelial dysfunction in humans may be temporally associated with myocardial perfusion defects and supports a role for the coronary epicardial and microcirculation endothelium in regulating myocardial perfusion. Myocardial ischemia may occur in humans with impaired endothelium-dependent coronary flow reserve of the coronary epicardial and microcirculation.