Electrophysiological effects of high-dose propranolol in dogs: evidence in vivo for effects not mediated by the beta adrenoceptor.

Closed-chest dogs anesthetized with morphine and chloralose were studied to determine if direct or nonspecific cardiac electro-physiological effects of propranolol occur at clinically relevant plasma concentrations and to differentiate the nonspecific effects from those due to beta adrenoceptor blockade. In 19 dogs, ventricular monophasic action potential durations (MAP), ventricular effective refractory periods (VERP) and His bundle electrograms (A-H and H-V intervals) were measured at base line and during sequential infusions of isoproterenol, dl-propranolol and dl-propranolol plus an isoproterenol infusion designed to overcome beta blockade. A mean plasma propranolol level of 979 +/- 344 ng/ml produced a significant (P less than .05) prolongation of A-H (95 +/- 20-115 +/- 13 msec), MAP (179 +/- 26-194 +/- 14 msec) and VERP (159 +/- 12-177 +/- 13 msec). Infusion of the beta agonist, isoproterenol, returned A-H and MAP to values not significantly different from base line, whereas VERP remained prolonged at 174 +/- 11 msec (P less than .05). No significant changes occurred in a control group of 14 dogs infused with saline. In eight additional dogs, infusions of d- and dl-propranolol, given on separate days, were used to produce equal beta blockade determined by individual isoproterenol sensitivity tests. A-H, H-V, MAP and ventricular strength-interval curves (VRP) and diastolic thresholds (DT) were measured and treatment vs. base-line changes (delta) with d- and dl-propranolol were compared.(ABSTRACT TRUNCATED AT 250 WORDS)