Comparison of the Cardiac Electrophysiologic Effects of NE-10064 with Sotalol and E-4031 and Their Modification by Simulated Ischaemia

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Abstract
The electrophysiologic effects of a new anti-arrhythmic agent NE-10064 were compared with known class III drugs, E-4031 and sotalol, in sheep Purkinje fibres paced at 1 Hz under normal and simulated ischaemic conditions. NE-10064 0.3-3 microM and sotalol 0.3-300 microM prolonged action potential duration at 90% of repolarization (APD90) and effective refractory period (ERP) concentration dependently without affecting APD50 under normal conditions. E-4031 0.3-300 microM prolonged APD50, APD90, and ERP concentration dependently. Percentage increases in APD90 of 20 +/- 6, 27 +/- 6, and 33 +/- 9 were calculated for NE-10064 3 microM, sotalol 300 microM, and E-4031 1 microM under normal conditions, respectively. The concentration-response curves for all three drugs were shifted to the right under simulated ischaemic conditions. The shift was more marked for NE-10064 and sotalol. Percentage increases in APD90 of 8 +/- 5, 13 +/- 2, and 23 +/- 4 were observed with NE-10064 3 microM, sotalol 300 microM, and E-4031 1 microM during simulated ischaemia. NE-10064 exhibits electrophysiologic characteristics similar to those of known class III agents. Its ability to prolong APD90 under normal conditions may explain its antiarrhythmic action in vivo.

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