Studies on the cardiotoxicity of ouabain

Pretreatment with reserpine in a catecholamine-depleting dosage schedule greatly increased the arrhythmic and lethal dose of ouabain in cats. Pretreatment with reserpine immediately before the administration of ouabain also increased these doses significantly but the effect was less marked than that produced by 24-h pretreatment. Tetrabenazine provided protection comparable to that of reserpine when the latter was given immediately before ouabain. This finding suggests that the protective action of reserpine may be partially of central origin. The initial effect of bretylium was to reduce the toxic dose, but this was not the case if pronethalol was also administered. Pronethalol alone significantly increased tolerance to ouabain. Adrenaline in doses that did not induce arrhythmias markedly reduced the toxic dose of ouabain. Acetylcholine and eserine both increased the toxic dose, and the effect was atropine-resistant. Atropine itself did not exert a significant effect. Compound P-286 had no effect on the arrhythmic dose of ouabain, but it did increase the lethal dose. Halothane anesthesia did not markedly alter the arrhythmic dose but definitely delayed cardiac arrest. Procaine infiltration of the superior atriocaval junction provided significant protection. The most marked protection, however, was seen with hypothermia. Although numerous agents were found capable of markedly altering the mean amount of ouabain required to evoke ectopic rhythm, very few significantly altered the additional amount required to cause death, once sinus dominance was lost.