Aging and digitalis sensitivity of cardiac muscle in rats.
The cause of the reduced tolerance of aged rats to the arrhythmogenic effect of ouabain was studied in left atrial and left ventricular muscle preparations obtained from 3-, 8- or 26-month old Fischer 344 rats. Under 1.5-Hz stimulation, the concentration-response curves for the positive inotropic effect of ouabain showed a tendency to shift to the left with age. The toxic effects occurred at lower ouabain or digoxin concentrations in the ventricular muscle obtained from senescent rats especially when the muscle was stimulated at a higher frequency (4 Hz), although differences in tolerance to the toxic effect of ouabain were not apparent in atrial muscle preparations stimulated at 1.5 Hz. No age-related difference in intracellular sodium or potassium concentration was observed in perfused ventricular muscle preparations paced at 1.5 Hz. There was no significant age effect on Na+-induced activation of Na+,K+-ATPase. In aged myocardium, however, the upstroke velocity of the action potential was reduced especially under high frequency stimulations, and the ability to follow high frequency stimulation was compromised. These results suggest that reserve capacity of the sodium pump is reduced in aged ventricular muscle, thereby elevating its sensitivity to the cardiac glycoside.
D000375:Aging; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004071:Digitalis Glycosides / Q000494:pharmacology*; D004077:Digoxin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis
D004071:Digitalis Glycosides; D010042:Ouabain; D004077:Digoxin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium