Does coronary vasodilation after adenosine override endothelin-1-induced coronary vasoconstriction?

Abstract

Endothelin-1 is a powerful coronary vasoconstrictor that is overexpressed in coronary artery disease. Adenosine is a powerful coronary vasodilator used for myocardial perfusion imaging to identify flow-limiting coronary artery stenosis. Therefore, in an animal model we tested the hypothesis that intracoronary endothelin-1 may cause myocardial perfusion abnormalities by positron emission tomography (PET) at resting conditions that may persist or only partially improve after intravenous adenosine stress in the absence of myocardial scar and flow-limiting stenosis. Fourteen dogs underwent serial PET perfusion imaging with rubidium-82 before and after subselective intracoronary infusion of endothelin-1, followed by intravenous and then intracoronary adenosine. Small physiological doses of endothelin-1 infused into the mid-left circumflex coronary artery caused quantitatively significant resting perfusion abnormalities that normalized after intracoronary adenosine but not consistently after intravenous adenosine used for diagnostic imaging. After effects of adenosine abated, resting perfusion defects returned, lasting up to 5 h in some animals. Cumulative doses of endothelin-1 caused perfusion defects that did not normalize after intravenous adenosine. In an animal model without myocardial scar or flow-limiting stenosis, intracoronary endothelin-1 causes visually apparent, quantitatively significant, long-lasting myocardial perfusion defects at resting conditions that may persist or only partially improve after intravenous adenosine used for diagnostic imaging. These results may potentially explain resting perfusion abnormalities or heterogeneity by clinical PET that may persist or only partially improve after adenosine stress perfusion imaging in the absence of myocardial scar and flow-limiting stenosis.