158 AMIODARONE (AM) ADVERSELY AFFECTS SINUS NODE (SN) FUNCTION IN VITRO

Abstract

AM is being used more frequently to control “resistant” childhood arrhythmias. As a Class III agent, AM supposedly acts by uniformly prolonging action potential (AP) duration and refractoriness. Because sinus slowing is observed clinically, we evaluated the acute effects of 0.68-34μg/ml AM on SN pacemaker activity using rabbit SN preparations and standard microelectrode techniques. Data were collected only from true SN pacemaker cells impaled continuously throughout the study. AM produced significant (p<0.05) concentration dependent decreases in spontaneous sinus rate (-6% at 6.8μg/ml; -12% at 34μg/ml), AP amplitude (-15% at 34μg/ml) and rate of phase 4 diastolic depolarization (-14%, -18%, -27% at 0.68, 6.8 & 34μg/ml respectively). Maximum diastolic & threshold potentials and Vmax also decreased significantly. Since AP duration did not increase, the fall in spontaneous rate was related solely to AM induced decreases in automaticity. Corrected SNRT and SACT were increased markedly by AM. In 4 preparations, SN exit or entrance block developed on prolonged exposure. The AM induced changes could not be reversed despite superfusion in AM-free medium for up to 1.5 hrs. Rather, SN function deteriorated further. AMs Class III actions cannot explain its effects on the SN. Since the automaticity and upstroke of SN pacemaker activity are dependent upon the slow inward Ca++ current (isi), AM may also possess Class IV (verapamillike) actions or marked antiadrenergic activity in-vitro.