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
2012
Lu, Hua Rong | Vlaminckx, Eddy | Cools, Frank | Gallacher, David J.
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 using micro-electrode recording. Arsenic (after 30 to 95min perfusion at 10μM) significantly prolonged APD₉₀, 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 APD₉₀ 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 0.1μM to 10μM at the standard perfusion-time of 15min per concentration, and after a continuous 90-min perfusion at 1μM and 1Hz did not induce these direct effects on APD₉₀, triangulation and EADs in isolated guinea-pig Purkinje fibers, but it at 1 µM elicited EADs in 2 out of 7 preparations after 90min at 0.2Hz. 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 APD₉₀ and induction of EADs in vitro.
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