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 b radycardias. The mechanism(s) underlying these phenomena are not well defined. Therefore we investigated (1) the chronotropic and dromotropi c 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: Guine a pig isolated, perfused hearts were instrumented for measurement of a trial 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 wer e measured to further define propofol's dromotropic effects and freque ncy-dependent behavior. Results: Propofol, in a concentration-dependen t manner, (1) slowed atrial rate and AV nodal conduction time in spont aneously beating hearts, (2) prolonged the S-H interval in atrially pa ced hearts, and (3) prolonged Wenckebach cycle length and effective re fractory period. The negative dromotropic effect of propofol was great er during atrial pacing than in spontaneously beating hearts. Furtherm ore, this effect was enhanced at faster pacing rates, indicating frequ ency-dependent behavior. Atropine significantly antagonized propofol-i nduced S-H interval prolongation. The results of competition binding s tudies also supported a M(2)-muscarinic receptor-mediated mechanism. C onclusions: We conclude that in the Isolated guinea pig heart, propofo l slows atrial rate and depresses AV nodal conduction in a concentrati on-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 ac tions, this anesthetic agent may impart antidysrhythmic protection to those patients susceptible to supraventricular tachycardias.