Beat-to-Beat Variability in Preload Unmasks Latent Risk of Torsade de Pointes in Anesthetized Chronic Atrioventricular Block Dogs

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  • Stams Thom RG
    Department of Medical Physiology, Division of Heart and Lungs, University Medical Center
  • Oosterhoff Peter
    Department of Medical Physiology, Division of Heart and Lungs, University Medical Center ICIN-Netherlands Heart Institute
  • Heijdel Atty
    Department of Medical Physiology, Division of Heart and Lungs, University Medical Center
  • Dunnink Albert
    Department of Medical Physiology, Division of Heart and Lungs, University Medical Center
  • Beekman Jet DM
    Department of Medical Physiology, Division of Heart and Lungs, University Medical Center
  • van der Nagel Roel
    ICIN-Netherlands Heart Institute Department of Cardiology, St. Antonius Hospital
  • van Rijen Harold VM
    Department of Medical Physiology, Division of Heart and Lungs, University Medical Center
  • van der Heyden Marcel AG
    Department of Medical Physiology, Division of Heart and Lungs, University Medical Center
  • Vos Marc A
    Department of Medical Physiology, Division of Heart and Lungs, University Medical Center

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Background:Beat-to-beat variability in ventricular repolarization (BVR) associates with increased arrhythmic risk. Proarrhythmic remodeling in the dog with chronic AV-block (CAVB) compromises repolarization reserve and associates with increased BVR, which further increases upon dofetilide infusion and correlates with Torsade de Pointes (TdP) arrhythmias. It was hypothesized that these pro-arrhythmia-associated increases in BVR are induced by beat-to-beat variability in preload.Methods and Results:Left ventricular monophasic action potential duration (LVMAPD) was recorded in acute (AAVB) and CAVB dogs, before and after dofetilide infusion. BVR was quantified as short-term variability of LVMAPD. The PQ-interval was controlled by pacing: either a constant or an alternating preload pattern was established, verified by PV-loop. The effect of the stretch-activated channel blocker, streptomycin, on BVR was evaluated in a second CAVB group. At alternating preload only, BVR was increased after proarrhythmic remodeling (0.45±0.14 ms AAVB vs. 2.2±1.1 ms CAVB, P<0.01). At CAVB, but not at AAVB, dofetilide induced significant proarrhythmia. Preload variability augmented the dofetilide-induced BVR increase at CAVB (+1.5±0.8 ms vs. +0.9±0.9 ms, P=0.058). In the second group, the increase in baseline BVR by alternating preload (0.3±0.03 ms to 1.0±0.8 ms, P<0.01) was abolished by streptomycin (0.5±0.2 ms, P<0.05).Conclusions:In CAVB dogs, the inverse relation between BVR and repolarization reserve originates from an augmented sensitivity of ventricular repolarization to beat-to-beat preload changes. Stretch-activated channels appear to be involved in the mechanism of BVR. (Circ J 2016; 80: 1336–1345)

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  • Circulation Journal

    Circulation Journal 80 (6), 1336-1345, 2016

    一般社団法人 日本循環器学会

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