Increase in Myocardial Digoxin Content Associated With Circulatory Volume Overload in the Dog

Abstract

1. Tritiated (12alpha-3H) digoxin (0-05 mg/kg body weight) was administered intravenously to conscious dogs with circulatory volume overload induced by previous creation of aorto-caval fistulae. Dogs were killed after 5 min, 1, or 4 h, and the myocardium sampled. Digoxin was extracted and counted and results compared to those in normal dogs. 2. At each time, myocardial digoxin concentration of all cardiac chambers in test dogs was greater than normal. Plasma digoxin concentration measured 5 min after administration was greater in dogs with fistulae but the subsequent levels were not different. 3. Anaesthetized and open-chest dogs with fistulae studied 5 min after digoxin administration had greater myocardial concentrations than similarly studied normal dogs. Although myocardial concentrations of digoxin were higher in anaesthetized than in conscious dogs the group with fistulae had higher values than did the normal group, as was the case for unanaesthetized dogs. 4. The basis for the effect of fistula is probably multifactorial. Diminised peripheral blood flow and peripheral digoxin delivery and uptake, resulting initially in higher digoxin levels in plasma perfusing the myocardium, may play a role. Increased myocardial mechanical and metabolic activity almost certainly are important. Cardiac hypertrophy, cardiac failure per se and plasma electrolyte changes are probably not. 5. The results are consistent with previously demonstrated reduced digitalis tolerance in the dog with circulatory volume overload.

The Effect of Heart Rate on Myocardial Ouabain Uptake and on the Susceptibility to Ouabain Cardiotoxicity in the Dog

“…Augmented myocardial digoxin concentration in dogs with haemorrhagic shock (Lloyd & Taylor, 1975) and with circulatory volume overload (Lloyd, Hopkins & Taylor, 1976) suggested that haemodynamic and/or myocardial mechanical factors influence myocardial glycoside uptake. While it is generally agreed that heart rate or contraction frequency modulates the pharmacological effects of digitalis on the myocardium, it has not been clear whether digitalis uptake by the myocardium is rate dependent.…”

THE INFLUENCE OF HEART RATE ON DIGOXIN‐INDUCED INHIBITION OF MYOCARDIAL NA+‐K+‐ATPASE ACTIVITY IN THE DOG

“…Myocardial uptake of both digoxin and ouabain are directly related to heart rate over a range of 50-200 beats/min and only two heart rate groups were studied here to optimize the chance of a decisive result. The protocol also depended upon the observation that myocardial uptake of digoxin is rapid (Lloyd, Hopkins & Taylor, 1976) and that, although cardiac pharmacological effects are more delayed, they should be near maximum after 1 h (Deurscher, Harrison & Coldman, 1972;Forester, Lewis, Weissler & Wilke, 1974).…”