title: Coronary endothelial dysfunction in humans is associated with myocardial perfusion defects.
abstract: BACKGROUND
  Coronary endothelial dysfunction may occur in patients with minimally obstructive coronary artery disease and angina, and potentially may cause myocardial ischemia.
  
  
  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 (%deltaCAD) was measured by quantitative coronary angiography, and percent change in coronary blood flow (%deltaCBF) 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 %deltaCAD and %deltaCBF by 24+/-5% and 241+/-46% in the LAD. In group 2, %deltaCAD decreased by 26+/-5%, but %deltaCBF increased by 54+/-17%. In group 3, perfusion defects were within the LAD territory, reflecting a decrease in %deltaCAD and %deltaCBF 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.
authors.affiliation: Division of Internal Medicine and Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minn 55905, USA.
authors.forename: D
authors.initials: D
authors.lastname: Hasdai
authors.forename: R J
authors.initials: RJ
authors.lastname: Gibbons
authors.forename: D R
authors.initials: DR
authors.lastname: Holmes
authors.forename: S T
authors.initials: ST
authors.lastname: Higano
authors.forename: A
authors.initials: A
authors.lastname: Lerman
mesh_terms: D000109:Acetylcholine; D000328:Adult; D000368:Aged; D002637:Chest Pain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003324:Coronary Artery Disease / Q000209:etiology*; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019275:Radiopharmaceuticals; D012307:Risk Factors; D017256:Technetium Tc 99m Sestamibi; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D019275:Radiopharmaceuticals; D017256:Technetium Tc 99m Sestamibi; D000109:Acetylcholine