Autonomic modulation of ventricular arrhythmia in cesium chloride-induced long QT syndrome.

Abstract

To evaluate autonomic influence on arrhythmogenesis in an animal preparation of triggered activity, we gave increasing doses of cesium chloride (0.125 to 5.0 mmol/kg iv) to 24 dogs distributed equally among four protocols of autonomic intervention: control, total denervation, beta-blockade, and left stellate stimulation. All dogs underwent atrioventricular node ablation followed by ventricular pacing. A left ventricular endocardial monophasic action potential (MAP) catheter allowed for detection of "MAP early afterdepolarizations" (mEAD). mEAD amplitude was measured relative to MAP amplitude. Cesium chloride (CsCl) increased both MAP duration (132% after 0.125 mmol/kg to 188% after 1.0 mmol/kg; p less than .001) and mEAD amplitude (20% after 0.125 mmol/kg to 49% after 1.0 mmol/kg; p less than .001) in a dose-dependent fashion. All dogs exhibited ventricular ectopy at roughly equivalent doses (0.88 +/- 0.5 mmol/kg). Cesium's peak effect on MAP characteristics, sinus node automaticity, and systolic blood pressure coincided with the onset of sustained ventricular tachycardia (VT). Whereas control and denervated dogs developed VT after similar doses of CsCl (1.21 +/- 0.1 vs 1.12 +/- 0.14 mmol/kg; p = NS), none of the six beta-blocked dogs developed sustained VT. Conversely, those dogs having undergone stellate stimulation developed VT after smaller doses (0.58 +/- 0.34 mmol/kg; p less than .001) and with earlier onset (12 vs 30 sec; p less than .025). After 0.5 mmol/kg of CsCl, left stellate stimulation augmented relative mEAD amplitude compared with control (51% vs 38%; p less than .001), whereas beta-blockade had little effect (39% vs 38%; p = NS). Autonomic intervention as such can affect the arrhythmogenicity of CsCl and similarly alter MAP characteristics. Furthermore, as beta-blockade can prevent sustained arrhythmia without eliminating mEADs, autonomic tone appears to modulate the expression of mEADs as sustained VT.