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005 Action potential amplitude alternans and ventricular arrhythmia in a rabbit model of heart failure
  1. R C Myles,
  2. F L Burton,
  3. S M Cobbe,
  4. G L Smith
  1. University of Glasgow, Glasgow, UK


Introduction In recent large studies abnormal microvolt T-wave alternans has failed to predict arrhythmic events, raising the possibility that it is not specifically associated with a pro-arrhythmic substrate. Although discordant repolarisation alternans has been mechanistically linked to re-entrant ventricular fibrillation (VF) in experimental models and alternans has been demonstrated to occur in pacing-induced heart failure, whether a mechanistic link between alternans and VF in heart failure is unknown. The aim of this study was therefore to examine the occurrence of repolarisation alternans in a rabbit model of heart failure and to investigate the link between alternans and in VF failing hearts.

Methods Heart failure was induced by coronary arterial ligation (n=11). Hearts from normal (n=12) and sham-operated rabbits (n=4) were used as controls. Rabbits were killed with an intravenous injection of 200 mg pentobarbital sodium. Hearts were excised and the left coronary artery was cannulated and perfused with oxygenated Tyrode's solution maintained at pH7.4 and 37 (n=15) or 30°C (n=16). Perfused left ventricular (LV) wedge preparations were dissected, loaded with voltage-sensitive dye and paced from the endocardium. An optical mapping system was used to record transmural optical action potentials (APs) during a progressive reduction in pacing cycle length (CL). Data analysis was performed using custom software employing standard algorithms.

Results Repolarisation alternans and ventricular arrhythmia were significantly more common in failing hearts at each temperature. Heart failure was not associated with an increased incidence of transmural discordant alternans. Progressive alternans of AP amplitude was observed during rapid pacing and was associated with both transmural conduction block and inducibility of VF.Abstract 005 Figure 1 A compares alternans of AP duration (APD) and AP amplitude in two failing hearts, one which developed VF during rapid pacing and the other which did not. In both hearts, APD alternans of a similar magnitude was present and in the VF prone heart, APD alternans was accompanied by marked alternans of AP amplitude. By contrast, in the VF resistant heart APD alternans was seen in isolation, without any significant alternans in AP amplitude. The mean magnitude of APD and AP amplitude alternans at the shortest CL captured during rapid pacing protocols as a function of mean pacing cycle length is shown in Figure B. The magnitude of relative AP amplitude alternans is greater than that of APD alternans. Although the magnitude of APD alternans was similar in VF prone and VF resistant hearts, the magnitude of AP amplitude alternans was greater in VF prone hearts.

Conclusions For the first time we describe the development of progressive changes in AP amplitude during alternans, and their relation to the development of conduction block. The data suggest an important role for amplitude alternans in the development of arrhythmias in failing hearts.

  • alternans
  • ventricular arrhythmia
  • heart failure

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