Electrophysiologic Effects of Isoproterenol and Beta Blocking Agents in Awake Dogs

Abstract

In awake, unrestrained animals beta adrenergic stimulation by isoproterenol increased heart rate and enhanced A-V conduction with no change of conduction in Purkinje tissue or ventricular activation time. The chronotropic and dromotropic responses to isoproterenol were abolished completely by the adrenergic antagonists, propranolol (0.2 mg/ kg) and pronethalol (2 mg/kg). Beta adrenergic blockade with propranolol produced no significant change of heart rate, A-V conduction, conduction velocity in Purkinje tissue, or ventricular activation time. In contrast to the above, pronethalol produced tachycardia, enhanced A-V conduction and prolonged ventricular activation slightly. The tachycardia which followed pronethalol was largely a consequence of vagal inhibition since it could be nearly abolished by prior administration of atropine. Propranolol produced no changes in the refractory period or excitability of atrial muscle. Pronethalol did not alter the excitability of atrial muscle but did prolong the atrial refractory period. Barbiturate anesthesia was found to prolong ventricular activation time, and in anesthetized animals both propranolol and pronethalol caused further depression of conduction. These data support the view that cardiac adrenergic activity has little or no influence on conduction in the ventricle, and suggest that the intensity of sympathetic activity in awake, unrestrained dogs is minimal. The differences in the responses of unanesthetized animals to propranolol and to pronethalol indicate that the latter agent has significant anticholinergic properties as well as certain extra-adrenergic actions on conduction. Failure of blocking doses of both the above agents to alter diastolic thresholds indicates that their anti-arrhythmic properties are not related to an effect on excitability. Beta adrenergic blocking agents appear to exert qualitatively as well as quantitatively different effects in awake and anesthetized preparations, an observation which should be taken into consideration when evaluating the pharmacologic properties of these compounds.