Effect of chronic potassium depletion on digitalis-induced inotropy and arrhythmias.
The arrhythmogenic and inotropic effects of digoxin were studied in normokalemic controls, chronically hypokalaemic, and potassium-repleted dogs instrumented to maintain heart rate, mean aortic pressure, mean left atrial pressure and autonomic tone constant. The duration of digoxin infusion needed to produce ventricular tachycardia (VT) was 56.7 +/- 3.6 min in depleted dogs, 69.0 +/- 2.7 min in controls (P less than 0.005 compared with depleted dogs), and 60.5 +/- 3.0 min in repleted dogs. Baseline left ventricular dP/dt (LV dP/dt) was similar in all groups. After digoxin, LV dP/dt increased more in controls and repleted dogs than in chronically hypokalaemic dogs; eg, after 45 min of digoxin infusion LV dP/dt increased 12.7 +/- 4.4% in hypokalaemic dogs; eg, after 45 min of digoxin infusion LV dP/dt increased 12.7 +/- 4.4% in hypokalaemic dogs, 43.8 +/- 3.3% in controls (P less than 0.025) and 39.3 +/- 8.5% in repleted dogs (P less than 0.025). The inotropic response to isoprenaline was also attenuated in the chronically hypokalaemic dogs. Plasma digoxin was similar in all groups. LV digoxin was also similar in control and depleted dogs. Although inhibition of Na+, K+-ATPase and the initial velocity of 3[H]-ouabain specific binding was less in depleted dogs at VT than in controls (P less than 0.05), the magnitude of this difference was not sufficient to explain the attenuated inotropic response. No histological abnormalities were seen on light or electron microscopy in any of the groups. Therefore chronic hypokalaemia has two deleterous effects. It increases sensitivity to the arrhythmogenic effects of digoxin and impairs the inotropic response to digoxin, and isoprenaline.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001665:Binding Sites; D004077:Digoxin / Q000378:metabolism / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007008:Hypokalemia / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology; D010042:Ouabain / Q000378:metabolism; D011188:Potassium / Q000627:therapeutic use; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013268:Stimulation, Chemical
D010042:Ouabain; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol; D011188:Potassium