Accentuated antagonism between beta-adrenergic and vagal effects on ventricular refractoriness in humans

The purpose of this study was to determine whether there is accentuated antagonism between sympathetic and vagal effects on ventricular refractory periods (VRPs) in humans. The effects of 0.04 mg/kg of atropine on the right ventricular effective and functional refractory periods were determined in the setting of beta-adrenergic blockade by propranolol (0.15 mg/kg loading dose, then 0.1 mg/min continuous infusion, group 1) and in the setting of beta-adrenergic stimulation by 25 or 50 ng/kg/min isoproterenol (groups 2 and 3, respectively). Groups 4 to 6 served as control groups. In group 4, VRPs were determined on three occasions separated by 10 min each in the absence of drug. VRPs also were determined on two occasions after infusion of propranolol (group 5) or 25 ng/kg/min of isoproterenol (group 6). Groups 1 to 4 consisted of 10 subjects each, and groups 5 and 6 consisted of five subjects each. VRPs were determined with the use of basic drive cycle lengths of 600, 500, 400, and 350 msec. Because of sinus tachycardia, sufficient data for comparison of groups 1 to 3 were available only at drive cycle lengths of 400 and 350 msec. Atropine significantly shortened the VRPs in groups 1 to 3, but the magnitude of atropine's effects in group 3 (5.3% to 5.8% shortening at drive cycle length of 350 msec) was significantly greater than in group 1 (2.6% to 3.0% shortening, p less than .05) Data from the control groups demonstrated that there was no effect of time on measurement of VRPs either in the drug-free state or in the presence of propranolol or isoproterenol. The results of this study indicate that cholinergic tone lengthens VRPs in the absence of background sympathetic activity and that this lengthening of VRPs may become accentuated during beta-adrenergic stimulation.