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 mol/L to 10^-4 mol/L) into the left anterior descending coronary artery (LAD). Percent change in CAD (%ΔCAD) was measured by quantitative coronary angiography, and percent change in coronary blood flow (%ΔCBF) was calculated using intracoronary flow Doppler. Coronary endothelium-independent vasodilation was examined using intracoronary adenosine and nitroglycerin. ^99mTc 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 %ΔCAD and %ΔCBF by 24 ± 5% and 241 ± 46% in the LAD. In group 2, %ΔCAD decreased by 26 ± 5%, but %ΔCBF increased by 54 ± 17%. In group 3, perfusion defects were within the LAD territory, reflecting a decrease in %ΔCAD and %ΔCBF 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.