Influence of alterations in sinus rate on determination of drug-induced changes in ventricular automaticity

The interrelationship between drug-induced changes in heart rate and drug-induced alterations in ventricular automaticity was studied in dogs with intact conduction systems and dogs with surgically-induced complete heart block. The effects of epinephrine (0.5 microgram-kg-1-min-1) and propranolol (1.0 mg-kg-1) on ventricular automaticity were shown to be partially concealed by heart rate changes produced by these agents. Partial concealment of ventricular automaticity changes was shown to result from an alteration in the degree of overdrive suppression secondary to rate changes. Changes in the degree of overdrive suppression have a masking effect on drug-induced alterations in ventricular automaticity and only when the degree of suppression was held constant could the full extent of drug effects on ventricular automaticity be determined. Following vagal stimulation or rapid pacing, the rate of recovery from overdrive suppression as measured by the number of ventricular beats in 30 s was shown to be a dependable index of ventricular automaticity. It was concluded that determinations of drug effects on ventricular automaticity should take into account changes in heart rate produced by the drug. A method for determining ventricular automaticity is described which matches overdrive suppression during the control period to that during drug action in order to cancel out the influence of changes in heart rate on ventricular automaticity.