The effect of metabolic inhibitors on strophanthidin-induced arrhythmias and contracture in cardiac purkinje fibers.
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.
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D000968:Antimycin A / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013327:Strophanthidin / Q000037:antagonists & inhibitors*; D013696:Temperature
D000963:Antimetabolites; D007461:Iodoacetates; D000968:Antimycin A; D013327:Strophanthidin; D003847:Deoxyglucose; D010100:Oxygen; D002118:Calcium; D019807:Iodoacetic Acid