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Figure 5 (A) Electrophysiological changes during a representative experiment employing sertindole (1.0 mg/kg) to induce torsades de pointes arrhythmia and pacing to prevent further arrhythmia. Two electrocardiogram leads, left ventricular (LV) and right ventricular (RV) monophasic action potential (MAP) recordings, are shown in each panel at a paper speed of 1 cm/s. Steady-state pacing (1,000 ms) or cycle length (CL) of the idioventricular rhythm (IVR) are shown at the top. QT interval and monophasic action potential duration (MAPD) are below each signal. Time (t) is relative to start of sertindole administration. Short-term variability (STV)LV is noted under each panel. In the control situation (b) with an RR interval of 1,340 ms and during pacing with a CL of 1,000 ms (a), STVLV were low and comparable. Sertindole administration prolonged repolarization, increased STVLV, induced extrasystoles (c), consequently precipitating torsades de pointes arrhythmia (d). When CL was decreased to 1,000 ms, torsades de pointes arrhythmia was temporarily prevented, and STVLV decreased along with minor changes in the duration of repolarization (e). (B) Sertindole prolonged LV MAPD independent of CL (*p < 0.05 [1-way repeated measures analysis of variance]; n = 6), whereas pacing to prevent recurrence of torsades de pointes arrhythmia did not decrease the LV MAPD. (C) Sertindole increased STVLV independent of CL, and STVLV decreased significantly as a consequence of pacing to stop torsades de pointes arrhythmia. (D) Representative examples of Poincaré plots of the LV MAPD during pacing, of the RR interval at IVR, and of the concomitant LV MAPD. Green = control group; brown = 1 mg/kg sertindole. Y-axes scaling identical to the X axes. Sertindole increases STVLV both when the RR variability is absent (pacing) and present (IVR); however, sertindole did not change the RR variability. (E) Composite data of the STVRR before (green) and after (brown) sertindole (p = NS; n = 6).
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