FREQUENCY-DEPENDENT EFFECTS OF PROPOFOL ON ATRIOVENTRICULAR NODAL CONDUCTION IN GUINEA-PIG ISOLATED HEART - MECHANISMS AND POTENTIAL ANTIDYSRHYTMIC PROPERTIES

Background: The use of propofol has been associated with episodes of bradycardias. The mechanism(s) underlying these phenomena are not well defined. Therefore we investigated (1) the chronotropic and dromotropic effects of propofol, (2) the frequency-dependent effects of propofol on the atrioventicular (AV) node, and (3) the physiologic mechanism(s) underlying propofol's effects on AV nodal conduction. Methods: Guinea pig isolated, perfused hearts were instrumented for measurement of atrial rate and AV nodal conduction time In spontaneously beating harts, or stimulus-to-His bundle (S-H) intervals in atrially paced hearts. In addition, the Wenckebach cycle length, effective refractory period and S-H interval prolongation to an abrupt increase in pacing rate were measured to further define propofol's dromotropic effects and frequency-dependent behavior. Results: Propofol, in a concentration-dependent manner, (1) slowed atrial rate and AV nodal conduction time in spontaneously beating hearts, (2) prolonged the S-H interval in atrially paced hearts, and (3) prolonged Wenckebach cycle length and effective refractory period. The negative dromotropic effect of propofol was greater during atrial pacing than in spontaneously beating hearts. Furthermore, this effect was enhanced at faster pacing rates, indicating frequency-dependent behavior. Atropine significantly antagonized propofol-induced S-H interval prolongation. The results of competition binding studies also supported a M(2)-muscarinic receptor-mediated mechanism. Conclusions: We conclude that in the Isolated guinea pig heart, propofol slows atrial rate and depresses AV nodal conduction in a concentration-dependent manner. The negative dromotropic effect of propofol shows frequency dependence and is predominantly mediated by M(2)-muscarinic receptors, Given the marked rate dependence of propofol's AV nodal actions, this anesthetic agent may impart antidysrhythmic protection to those patients susceptible to supraventricular tachycardias.