RSD1019 suppresses ischaemia-induced monophasic action potential shortening and arrhythmias in anaesthetized rabbits

1 The electrophysiological actions of lidocaine, tedisamil and RSD1019 were assessed on normal and ischaemic cardiac tissue using monophasic action po tentials (MAPs) recorded from the epicardium of anaesthetized rabbits. Drug effects on ischaemia-induced arrhythmias were assessed simultaneously in t he same rabbits. 2 Lidocaine, infused at 2.5, 5 and 10 mu mol kg(-1) min(-1) i.v., accelerat ed and worsened the electrophysiological derangement caused by ischaemia, h ad profibrillatory actions and reduced the time to the occurrence of ventri cular fibrillation (VF) relative to controls. 3 Tedisamil, infused at 0.063, 0.125 and 0.25 mu mol kg(-1) min(-1) i.v., p rolonged MAP duration at 90% repolarization (MAPD(90%)) before induction of ischaemia in a dose-related manner; however, this effect was not maintaine d 5 min after induction of ischaemia. Tedisamil had no significant antiarrh ythmic actions over the dose-range tested. 4 RSD1019, infused at 2, 4 and 8 mu mol kg(-1) min(-1) i.v., produced a sma ll increase in MAPD(90%) before induction of ischaemia and only at the high est dose tested. In contrast to tedisamil, RSD1019 suppressed ischaemia-ind uced MAP shortening assessed 5 min after induction of ischaemia. This effec t was dose-related. RSD1019 completely prevented ischaemia-induced tachyarr hythmias at the mid and highest infusion levels tested. 5 The results of this study illustrate a pathologically targeted approach f or preventing ischaemia-induced arrhythmias. Suppression of ischaemia-induc ed MAP shortening, demonstrated herein for RSD1019, represents a novel anti fibrillatory approach.