Key result
Bilateral stellectomy reduces TdP inducibility from 100% to ~12% in chronic AV block.
Why the study?
Cardiac autonomic adaptations and neuromodulatory approaches in non-ischemic cardiac injury are poorly understood, particularly in chronic AV block.
Does autonomic neuromodulation reduce dofetilide-induced Torsade de Pointes in a chronic AV-block dog model?
Does autonomic neuromodulation reduce dofetilide-induced Torsade de Pointes in a chronic AV-block dog model?
Absolute Event Rate: 11.8% vs 100%
p-value: p=<0.005
In a canine model of chronic AV block, pro-arrhythmic autonomic remodeling occurs and can be reversed by mechanical denervation via bilateral stellectomy to suppress Torsade de Pointes, whereas pharmacological blockade is ineffective.
Background Cardiac autonomic adaptations and neuromodulatory approaches in non-ischemic cardiac injury are poorly understood. Objectives This study explored neural remodeling in chronic atrioventricular-block (CAVB) dogs and compared antiarrhythmic efficacy of pharmacological and mechanical neuromodulatory interventions. Methods Dogs serially underwent baroreflex sensitivity (BRS) testing with nitroprusside and left stellate ganglion (LSG) stimulation at sinus rhythm (SR; n=5), Acute AV block (AAVB, n=6), CAVB5 (five weeks, n=8) and CAVB11 (11 weeks, n=4). Electrophysiological and anti-arrhythmic effects of autonomic nervous system modulation (hexamethonium (20mg/kg/5'), propranolol (0.3mg/kg/3') or bilateral stellectomy) were assessed in combination with IK,r-blocker dofetilide (25μg/kg/5'). High-resolution mapping was performed to calculate spatial dispersion of repolarization (DoR). LV contractility was derived from a LV pressure catheter. TdP-inducibility was defined as ≥3 episodes within ten-minutes following start of dofetilide. LSG of CAVB11 and SR dogs (n = 4/group) were histologically examined. Results BRS decreased from 2.6±2.0 (SR) to 0.3±0.15 ms/mmHg (CAVB11; p<0.05). LSG stimulation caused an increase of DoR from +1.0±0.1% at AAVB to +3.0±1.0% at CAVB11 (p<0.05). Hexamethonium and propranolol failed to suppress arrhythmias, but bilateral stellectomy decreased TdP-inducibility (from 17/17 to 2/17; p<0.005). Stellectomy was not associated with changes in repolarization parameters, but significantly decreased contractility (p<0.05). Histologically, neuronal adaptation was reflected in significant increases in LSG neuronal area and diameter. Conclusion Autonomic remodeling in CAVB dogs is characterized by decreased BRS, increased DoR upon LSG stimulation and LSG neuronal hypertrophy. Pro-arrhythmic effects are reversed by bilateral stellectomy, but not by pharmacological approaches.
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Weperen et al. (2026) studied Chronic atrioventricular block / Torsade de Pointes arrhythmias (n=17). Bilateral stellectomy vs. Baseline (before stellectomy) / Pharmacological autonomic modulation was evaluated on TdP-inducibility (≥3 episodes within ten-minutes following start of dofetilide) (p=<0.005). Bilateral stellectomy significantly decreased Torsade de Pointes inducibility from 100% to 11.8% in dogs with chronic atrioventricular block (p<0.005).
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