Transmural distribution of blood flow during activation of coronary muscarinic receptors.

The role of coronary muscarinic receptors in the distribution of transmural blood flow across the left ventricular wall of the working heart was studied in anesthetized open-chest dogs. Tissue blood flow in subepicardium, midmyocardium, and subendocardium was determined with radioactive microspheres before and during activation of muscarinic vasodilator receptors by intracoronary infusions of acetylcholine. Myocardial and coronary vascular beta-receptors were blocked by sotalol (2.0 mg/kg iv). Equivalent submaximal coronary vasodilator doses of acetylcholine and adenosine were compared for effects on transmural blood flow. Intracoronary infusions of acetylcholine (5.0 and 10.7 micrograms/min) produced a dose-related increase in the subendocardial-subepicardial blood flow ratio (endo/epi) from 1.07 to 1.32 and 1.57, respectively. A progressively larger decrease in coronary vascular resistance occurred in the subendocardium than midmyocardium or subepicardium following acetylcholine administration. In contrast, intracoronary administration of adenosine (54.4 micrograms/min) produced no change in endo/epi. Atropine effectively blocked acetylcholine-induced coronary vasodilation but not vasodilation produced by adenosine. Neither agent affected heart rate, left ventricular pressure, coronary perfusion pressure, or myocardial contractility. These results suggest that activation of muscarinic coronary vasodilator receptors redistributes blood flow preferentially to the subendocardium independent of cardiac mechanical influences.