The effect of theophylline alone and in combination with ouabain on the isolated dog heart

Abstract

A comparative study of the inotropic effects of theophylline and ouabain as well as a study of the interaction between the two pharmacological agents were carried out in the nonfailing Starling heart-lung preparation modified to permit metabolic studies. Single doses of theophylline ranging between 100 to 200 mg added to the venous reservoir produced consistent increases in myocardial contractile force, as gauged by the maximal rate of rise of left ventricular pressure, dp/dt, 73%; systemic output, 28%; coronary output, 277%; total cardiac output, 41%; heart rate, 27%; left ventricular work, 45% and myocardial oxygen consumption, 43%. In addition, systolic time decreased consistently by 15%. 20 min and 30 min after the onset of an ouabain infusion of 5μg per min, which was started 15 min after the addition of theophylline, there was further increase in dp/dt to 87% and 107%, respectively, with no significant change in the remaining parameters from the levels attained 15 min after the administration of theophylline. As compared to ouabain administered alone, ouabain administered at peak effect of theophylline led to an earlier occurence of ventricular arrhythmias and death. It may be concluded from this study that maximally effective doses of theophylline brought about an increase in dp/dt which is greater than that brought about by maximal “therapeutic” doses of ouabain. Secondly, ouabain administered after the peak effect of theophylline was exerted led to an additional increase in dp/dt implying that the mechanisms underlying the inotropic action of each drug are different. Thirdly, at constant aortic pressure, heart rate, left ventricular enddiastolic and left atrial pressures, ouabain in the presence of theophylline brought about an increase in myocardial contractility, as gauged by an increase in dp/dt, without a concomitant increase in myocardial oxygen consumption, thus confirming earlier results obtained with ouabain alone. Fourthly, ouabain administered at peak effect of theophylline led to an earlier occurrence of ventricular arrhythmias and death.