The effect of different metabolic inhibitors on the induction of spontaneous rhythms by
strophanthidin was studied in canine cardiac Purkinje fibers perfused in vitro. Both the electrical and mechanical activity were recorded.
Strophanthidin caused its usual effects (an increase and then a decrease in force, a steepening of diastolic depolarization, spontaneous rhythms and inexcitability, but no
contracture). When
strophanthidin administration was repeated in the presence of depressed oxidative phosphorylation (
antimycin and
hypoxia), the force increased less and spontaneous rhythm occurred without the development of
contracture. When
strophanthidin was administered in the presence of blockade of glycolysis (iodoacetic acid and 2-deoxy-D-glucose),
strophanthidin increased force even more than in the control test but steepened diastolic depolarization less or not at all and induced
contracture. In some preparations, spontaneous rhythms developed but then only before the development of
contracture.
Hypothermia also increased the duration of the twitch and prevented the oscillatory potentials.
Strophanthidin-induced arrhythmias were present in
hypoxia but were prevented in
hypoxia plus
2-deoxy-D-glucose. When metabolic blockade was severe (irreversible stage of
antimycin action),
contracture also developed, but spontaneous activity failed to appear. It is concluded that the oscillatory potentials induced by cardiac
steroids are sensitive to blockade of glycolysis or severe metabolic blockade, possibly as a consequence of an impaired reuptake of
calcium into sarcoplasmic reticulum.