The effect of heart rate on myocardial ouabain uptake and on the susceptibility to ouabain cardiotoxicity in the dog.

Abstract

SUMMARY1. Tissue ouabain concentrations were estimated 30 min after intravenous 3H‐ouabain administration to sedated dogs, the heart rates of which were adjusted to range between 50 and 200 beats/min. Significant correlations were present between heart rate and ouabain content in left ventricle (r=0.93, P< 0.001), in right ventricle and left atrium. In contrast, no significant correlations were present between heart rate and ouabain content in liver, in renal cortex, skeletal muscle or plasma.2. To determine the functional effect of the greater myocardial ouabain uptake associated with higher heart rate, anaesthetized open‐chest dogs were studied. The heart rates of two groups were controlled at 199 ± 9 (s.d.) beats/min and 90 ± 14 beats/min during ouabain administration, and 30 min later, at a common heart rate, acetyl strophanthidin tolerance tests were performed.3. Acetyl strophanthidin infusion induced ventricular tachycardia significantly earlier, after a correspondingly lower dose in the fast heart rate group (P<0.01). Significant inverse correlations were present between the concentrations of ouabain in both left and right ventricular muscle and the duration of acetyl strophanthidin infusion.4. The results indicate that higher heart rate is associated with greater myocardial ouabain uptake and that this ouabain is functionally active.