INOTROPIC AND TOXIC RESPONSES TO ACETYLSTROPHANTHIDIN IN YOUNG ANIMALS: RELATIONSHIP OF HYPERCAPNIA AND BETA ADRENERGIC BLOCKADE

¹ Departments of Pediatrics and Pathology, Yale University School of Medicine, New Haven, Connecticut

Inotropic and toxic arrhythmic responses to acetylstrophanthidin were evaluated in young puppies and piglets. These findings were compared with those during acute hypercapnic acidemia and beta adrenergic blockade with practolol. Acetylstrophanthidin administered in an initial dose of 20 µg/kg, followed by a continuous infusion of 1 µg/kg/min induced ventricular premature contractions at a similar dose in blocked or unblocked animals. The toxic dose was also unaltered by hypercapnic acidemia. Inotropic responses were assessed by measuring left ventricular dP/dt_max and end-diastolic pressure under conditions of constant heart rate and arterial pressure. In the presence of beta blockade, large increments in contractility occurred with the initial dose and increased linearly with continuous acetylstrophanthidin infusion until the appearance of toxicity. Hypercapnic acidemia did not alter contractility responses in the puppies but the maximum responses were moderately attenuated in piglets. In puppies without practolol blockade, the positive inotropic responses were approximately 50% less than in blocked animals. During hypercapnic acidemia in unblocked puppies, the glycosideinduced increase in contractility was undiminished. This evidence supports the view that in the normal heart reflex withdrawal of sympathetic activity partially offsets the direct positive inotropic effect of digitalis and that increased sympathetic activity engendered by hypercapnic acidemia can override this effect.