Effects of ischemia and reperfusion on myocardial uptake of tritiated digoxin

The effect of coronary reperfusion on the uptake of cardiac glycosides by ischemic myocardium was studied in 17 open chested dogs undergoing anterior wall infarction produced by snaring confluent branches of the left coronary system. Epicardial electrograms delineated ischemic zones of S-T elevation, border, and nonischemic zones. Animals were reperfused by snare release 1, 2, and 6 hr after occlusion. After 15 min of reperfusion, 1.0 mg of [3H] digoxin was given intravenously, and 2 hr later the hearts were excised and endocardial (endo) and epicardial (epi) samples from each zone were analyzed for [3H] digoxin concentration. In five dogs occluded for 1 hr and reperfused, [3H] digoxin uptake was comparable in endo and epi layers of all three zones. In six dogs reperfused after 2 hr of occlusion, mean (+/-S.E.) [3H] digoxin concentrations (nanograms per gm) were significantly reduced by 54 percent in endo (111 +/-18) and 35 percent in epi (151 +/- 23) layers of the ischemic zone as compared with the mean nonischemic concentration (endo249 +/- 34; epi 239 +/- 34). Border zone endo and epi [3H] digoxin uptake was reduced by 21 and 17 percent, respectively. In six dogs reperfused after 6 hr of occlusion, [3H] digoxin uptake in the ischemic zone was markedly reduced by 85 percent in endo (34 +/- 4) and 60 percent in epi (86 +/- 12) layers as compared with the nonischemic concentration (endo 232 +/- 19; epi 217 +/- 15). Border zone uptake was decreased by 54 percent in endo and 38 percent in epi regions. We conclude that coronary reperfusion between 2 and 6 hr of coronary occlusion is associated with markedly reduced myocardial digoxin uptake, more pronounced in subendocardial regions of ischemic tissue. This alteration in digoxin binding by reperfused ischemic myocardium is consistent with ischemia-induced structural or functional alterations in the putative digitalis receptor, (Na++K+)-ATPase.