Direct effects of arsenic trioxide on action potentials in isolated cardiac tissues: Importance of the choice of species, type of cardiac tissue and perfusion time

Introduction: The aim of the present study was to evaluate direct/acute effects of arsenic trioxide on action potentials (APs) in isolated cardiac tissues, and to investigate if the choice of species and tissue and the duration of the perfusion play a role in arsenic-induced acute/direct prolongation of AP/QT. Methods and results: Direct electrophysiological effects of arsenic trioxide were measured in cardiac tissues isolated from four different species usingmicro-electrode recording. Arsenic (after 30 to 95 min perfusion at 10 mu M) significantly prolonged APD(90), increased triangulation of the AP and elicited early afterdepolarizations (EADs) only in isolated guinea-pig and dog Purkinje fibers but not in rabbit and porcine (minipig) Purkinje fibers. Arsenic induced a prolongation of the APD(90) and increases in triangulation and the occurrence of EADs was not observed in papillary muscles of guinea-pigs and rabbits. Arsenic at 4 increasing concentrations from 0.1 mu M to 10 mu M at the standard perfusion-time of 15 min per concentration, and after a continuous 90-min perfusion at 1 mu M and 1 Hz did not induce these direct effects on APD(90), triangulation and EADs in isolated guinea-pig Purkinje fibers, but it at 1 mu M elicited EADs in 2 out of 7 preparations after 90 min at 0.2 Hz. Discussion: The present study demonstrates that the choice of species and cardiac tissue as well as perfusion-time play important roles in arsenic-induced direct/acute effects on APD(90) and induction of EADs in vitro. (C) 2012 Published by Elsevier Inc.