Effects of ischemia and coronary reperfusion on myocardial digoxin uptake.
The effects of coronary reperfusion on the uptake of digoxin by ischemic myocardium were studied in 17 open chest dogs undergoing anterior wall infarction produced by snaring confluent branches of the left coronary arterial system. Epicardial electrograms delineated ischemic, border and nonischemic zones. The hearts were reperfused by snare release after 1, 2 and 6 hours of occlusion. After 15 minutes of reperfusion, 1.0 mg of tritiated digoxin (3H-digoxin) was given intravenously, and 2 hours later the hearts were excised and endocardial and epicardial samples from each zone were analyzed for 3H-digoxin concentration. In another group of eight dogs regional myocardial blood flow was assessed utilizing 15 mu of radio-labeled microspheres administered during occlusion and reperfusion. In five dogs with 1 hour of coronary occlusion and subsequent reperfusion, 3H-digoxin uptake was comparable in endocardial and epicardial layers of all three zones. In six dogs undergoing reperfusion after 2 hours of occlusion, mean 3H-digoxin concentration was significantly (P less than 0.001) reduced from the mean nonischemic concentration, by 54 percent in endocardial and 35 percent in epicardial layers of the ischemic zone. Border zone endocardial and epicardial 3H-digoxin uptake was reduced by 21 percent and 16 percent, respectively (P less than 0.05). In six dogs undergoing reperfusion after 6 hours of occlusion, 3H-digoxin uptake in the ischemic zone was significantly (P less than 0.001) reduced by 85 percent in endocardial and 60 percent in epicardial layers from the concentration in the nonischemic zone. Border zone uptake was decreased by 54 percent in endocardial and 36 percent in epicardial regions (P less than 0.01). These alterations of in vivo digoxin binding could not be explained by impaired reflow of blood to ischemic myocardium. We conclude that coronary reperfusion after 2 to 6 hours of occlusion is associated with a marked reduction in myocardial digoxin uptake, which is more pronounced in subendocardial than in subepicardial regions of ischemic tissue.
D000818:Animals; D003326:Coronary Circulation; D003327:Coronary Disease / Q000378:metabolism*; D004077:Digoxin / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D009206:Myocardium / Q000378:metabolism*
D004077:Digoxin