Search

We attempted to correlate inotropic and eletrophysilogic digitoxin effects with serum digitoxin concentrations during 8 hr after a single dose. Eight pentobarbital-anesthetized Labrador dogs were given 2.0 mg digitoxin intravenously. Left heart catheterization and His bundle registration were performed. acing and programed electrical stimulation were used to determine heart rate-independant changes in dP/dt, intra-atrial, atrioventricular (AV), His-Purkinje, and intraventricular conduction velocity. The effective (A-ERP) and functional (A-FRP) refractory periods of the atrium and the functional nodal refractory period (AV-FRP) were measured. Serum digitoxin concentrations were determined by radioimmunoassay. Median serum digitoxin half-time was 5.7 hr. The dP/dt increased after digitoxin, with maximum values after 2 hr. Digitoxin concentration correlated with the inotropic response after 4 hr. Heart rate fell significantly within 2 min and remained below control values for the 8 hr observation period concimitant with an increase in AV-nodal conduction time and AV-ERP increased significantly in the late elimination phase, while A-FRP increased slightly initially and remained high. No consistent correlation was found between the electrophysilogic variables and serum concentrations. We conclude that the two main effects of digitoxin, the inotropic and electrophysiologic, are dissociated in the elimination phase after a single dose.

We tested the electrophysiologic effects of vagus stimulation in six dogs in the presence or absence of beta-adrenoreceptor blockade. Monophasic action potentials were obtained by the suction electrode technique and programmed electrical stimulation was used to determine heart rate-independent changes in 50 and 90% repolarization times and in the effective (V-ERP) and functional (V-FRP) refractory periods of the right ventricle. Vagus stimulation decreased heart rate both in the presence and in the absence of beta-adrenoceptor blockade. It also increased action potential duration and refractoriness during high sympathetic tone induced by pentobarbital anesthesia. The effect is probably due mainly to inhibition of beta 1-adrenoreceptors, since it was decreased by beta 1-adrenoceptor blockade with atenolol. We conclude that stimulation of the vagus has antiarrhythmic effects in ventricles under high sympathetic stimulation.

We studied the effects of three different beta-adrenoreceptor-blocking drugs (atenolol, acebutolol, and propranolol) on the duration of monophasic action potentials and refractoriness of the right ventricular myocardium in closed-chest dogs. Pentobarbital anesthesia, which is known to increase the sympathetic tone, was used. Monophasic action potential recordings were obtained by the suction electrode technique, and refractoriness was measured by means of programmed electrical stimulation. A stepwise decrease in stimulation intervals from 350 to 300, 260, and 230 ms caused a progressive decrease in refractoriness as well as in the duration of the monophasic action potential. Intravenous injections of atenolol 0.5 mg/kg, acebutolol 2.0 mg/kg, and propranolol 0.5 mg/kg after pretreatment with atropine each increased the times for 50 and 90% repolarization of the monophasic action potential at each stimulation interval. The effective and the functional refractory periods paralleled the changes in the action potential duration in all experiments. We conclude that beta-adrenoreceptor blockade in the presence of adrenergic receptor stimulation prolongs ventricular refractoriness and action potential duration, and that the presence or absence of cardiac selectivity or slight intrinsic sympathomimetic activity plays no role in this process. These results suggest that if the antiarrhythmic action of beta-blocking drugs is due to prolongation of ventricular refractoriness, all types of these drugs may be expected to be equally effective as therapeutic agents.

Inotropic and electrophysiologic effects in dogs of a single dose of digitoxin with and without autonomic blockade with propranolol plus atropine were observed for 8 hr. Left heart catheterization and His bundle registration were performed in 14 Labrador dogs anesthetized with pentobarbital. Pacing and programmed electrical stimulation were used to determine heart rate-independent changes in dP/dt, intra-atrial, AV nodal, His-Purkinje, and intraventricular conduction velocity. The effective and the functional refractory periods of the atrium, and the functional nodal refractory period (AV-FRP) were measured. Six dogs were given propranolol 0.5 mg/kg plus atropine 0.05 mg/kg every hour. After determination of inotropic and electrophysiologic parameters, digitoxin (2.0 mg) was given to 5 of the dogs, while 1 dog served as control. The other 8 dogs were given only digitoxin (2.0 mg). The dP/dt increased after digitoxin in both groups with maximum values after 2 hr. The autonomic nervous system had only minor influence on changes in contractility caused by digitoxin. The marked fall in heart rate and increase in A-H time (i.e., AV nodal conduction time) and AV-FRP after digitoxin were almost completely blocked by atropine and propranolol. Minor increases in A-H time and AV-FRP indicated a slight direct effect of digitoxin on the AV node.