Harrison, Carlos E.

Ten intact dogs were subjected to hemodialysis against a solution of low-sodium content to determine the influence of sodium depletion on myocardial binding of digoxin- 3 H. Serial determinations of serum sodium, potassium, chloride, bicarbonate, pH, and osmolality, of cardiac output, and of cardiac rhythm were obtained in these and in 10 control dogs dialyzed against the standard solution. A dose of digoxin- 3 H (0.05 mg/kg) was given intravenously after start of the dialysis and the animals were killed 1 hour afterward for measurement of myocardial radioactivity, potassium, and sodium. Significant depletion of serum sodium and chloride and myocardial sodium ( P < 0.001) occurred in all animals dialyzed against the low-sodium solution. No significant changes occurred in other serum electrolytes or pH; osmolality was maintained constant by a slow intravenous drip of 25% urea or mannitol. Myocardial radioactivity was reduced in sodium-depleted animals by 50% ( P < 0.001). The Na-K ratio was 0.40 in the myocardium of control animals and 0.26 in sodium-depleted animals. It was concluded that depletion of body sodium inhibits binding of digitalis glycosides to the myocardium during the first hour after injection of the dose.

Depressed myocardial contractility with paradoxically increased oxygen consumption has been demonstrated in previous studies of pressure overload hypertrophy. To determine whether altered mitochondrial respiration participates in the abnormal energetics of this muscle, right ventricular hypertrophy (RVH) was produced in 12 cats by pulmonary artery banding. A polarographic muscle bath was used to study eight control and eight RVH papillary muscles, and the respiration of mitochondria isolated from these right ventricles was characterized. RVH muscles demonstrated depressed force-velocity and length-tension curves. The myocardial oxygen consumption per gram of peak active tension was increased from 0.65 ± 0.05 nliters/mg beat -1 (control) to 1.10±0.07 nliters/mg beat -1 (RVH) ( P <0.001). Abnormal mitochondrial respiration was shown by an increase in the rate of state 4 oxygen consumption from 12.5±0.8 natoms/mg min -1 (control) to 19.9±0.8 natoms/mg min -1 (RVH) ( P < 0.001). The altered oxygen cost of active isometric tension in the RVH muscles was linearly correlated with the altered rate of mitochondrial state 4 oxygen consumption ( r = 0.91). Ruthenium red, a compound that blocks mitochondrial calcium uptake, reduced the rate of RVH state 4 oxygen consumption to the control level. The present study suggests a mechanism for the abnormal myocardial oxygen consumption in pressure overload hypertrophy and relates it to nonphosphorylating mitochondrial respiration linked to calcium transport.