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Acta Physiologica 2009; Volume 197, Supplement 675
Joint meeting of The Slovenian Physiological Society, The Austrian Physiological Society and The Federation of European Physiological Societies
11/12/2009-11/15/2009
Ljubljana, Slovenia
ROLE OF VENTRICULAR ACTIVATION FOR ARRHYTHMOGENESIS IN THE CAVB DOG MODEL
Abstract number: L31
Stams1 Thom R.G., Winckels1 Stephan K.G., Thomsen1 Morten B., Beekman1 Jet D.M., van der Nagel1 Roel, Vos1 Marc A.
1Department of Medical Physiology, University Medical Center Utrecht, The Netherlands
For years, the anesthetized dog with chronic, complete AV block (CAVB) is used to screen (non-)cardiovascular drugs for proarrhythmic properties. This model is very sensitive and specific for drug-induced Torsade de Pointes: proarrhythmic drugs show TdP incidences upwards to about 80%, whereas not all QT-prolonging drugs will initiate TdP. Creation of AV block will lead abruptly to a) bradycardia (decrease in heart rate from 110 towards 50 bpm), b) AV-dyssynchrony and c) altered (variable) ventricular activation. In most animals, the idioventricular rhythm (IVR) will originate from the left ventricular (LV) low septum. In time, ventricular remodeling will occur that can be seen as a) electrical (prolongation of repolarization duration and increase of beat-to-beat variability of repolarization duration), b) contractile (doubling of the peak rate of LV pressure rise (LV dP/dtmax) to preserve cardiac output) and c) structural (biventricular hypertrophy) remodeling.
To control ventricular remodeling and arrhythmogenesis, we have set out a number of experiments to investigate the relevance of ventricular activation. In the first group (9 dogs), a pacemaker lead was implanted in the high septal region (4 weeks CAVB) and dofetilide was used as the arrhythmogenic challenge. It was shown that, compared to normal CAVB dogs with IVR, maintenance of normal activation with high septal pacing (HSP) at lowest captured ventricular rate decreased baseline electrical remodeling (LV MAPD increase: 14% in HSP vs. 39% in IVR dogs) and TdP-susceptibility with about 50%: TdP incidence was lowered from 7/9 (78%) towards 4/9 animals (44%). In a second group (n=8), right ventricular apex (RVA) pacing at lowest captured ventricular rate was maintained for 3 weeks. Electrical remodeling was attenuated (LV MAPD increase in baseline: 5%), whereas the incidence of dofetilide-induced TdP was 5/8 animals (63%). After dofetilide, the decreased repolarization reserve was unmasked.
This set of experiments showed that physiologic activation (HSP) diminished TdP-susceptibility. Altered ventricular activation results in more proarrhythmia after dofetilide, whereas the origin of ventricular activation is less important.
To cite this abstract, please use the following information:
Acta Physiologica 2009; Volume 197, Supplement 675 :L31