Ischemic-induced alterations in cardiac sensitivity to digitalis.
Intravenous infusion of acetylstrophanthidin to 6 dogs, after a 60 min left anterior descending coronary artery occlusion, was associated with a 43.0 +/- 10.5% decrease in the dose of digitalis needed to produce ventricular arrhythmias as compared to the pre-ischemic dose (97.5 +/- 8.0 microgram/kg). Reperfusion of the ischemic region for 2 h after a 90 min occlusion resulted in a 54.4 +/- 6.7% decrease in the arrhythmogenic dose. Direct intracoronary infusions of digitalis into the ischemic region, after a 90 min coronary occlusion followed by 2 h of reperfusion, was associated with a 47.7 +/- 6.4% decrease in the dose of digitalis needed to produce arrhythmias. The pre-ischemic (control) arrhythmogenic dose of digitalis via the intracoronary infusion method was 1.5 +/- 0.3 microgram/kg (mean +/- S.E.M. of 7 dogs). Sodium pump activity, estimated from the ouabain-sensitive 86Rb uptake in sodium-loaded ventricular slices, was significantly higher in slices obtained from the ischemic regions (6.84 +/- 0.30 nmoles 86Rb/mg dry wt. (mean +/- S.E.M.), than from the non-ischemic regions (3.43 +/- 0.64 nmoles 86Rb/mg dry wt.). Sensitivity of the sodium pump activity to the inhibitory effect of ouabain also was increased in the ischemic regions as indicated by a shift in the log dose--response curve to the left. Thus, it appears that there is an increase in myocardial sensitivity to the toxic effect of digitalis after temporary ischemia and it appears to be related to an increase in the sensitivity of the Na+,K+-ATPase or sodium pump to the inhibitory effect of digitalis.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D004071:Digitalis Glycosides / Q000494:pharmacology*; D004285:Dogs; D006321:Heart / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000503:physiopathology; D011868:Radioisotopes; D012413:Rubidium; D012964:Sodium / Q000378:metabolism; D013327:Strophanthidin / Q000494:pharmacology; D013997:Time Factors
D004071:Digitalis Glycosides; D011868:Radioisotopes; D013327:Strophanthidin; D012964:Sodium; D012413:Rubidium