Effect of a toxic in vivo dose of ouabain on guinea-pig heart mitochondria

The effects of toxic doses of ouabain on two parameters of mitochondrial activity, oxidative phosphorylation and calcium uptake were examined. Ouabain was injected intraperitoneally into guinea-pigs until signs of severe intoxication appeared. State 3 oxygen consumption (Q_O2, State 3, in natom oxygen/mg/min) of isolated heart mitochondria was 314 ± 16 and 281 ± 16 (glutamate-malate) for treated and control group, respectively; 225 ± 21 and 207 ± 23 (pyruvate-malate), and 251 ± 12 and 230 ± 13 (succinate), respectively. The rate of calcium uptake was 411 nmol Ca²⁺/min/mg for treated and 329.6 nmol Ca²⁺/min/mg for control. The rate of calcium release was the same in control and treated groups.The data suggest that increases of respiration and calcium uptake in vitro, if they reflect similar increases in vivo, may contribute to digitalis intoxication by intracellular redistribution of calcium.