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.

Electrophysiological mechanisms in a canine model of erythromycin-associated long QT syndrome.

“…The difference might possibly be a result of circulating catecholamines released from the adrenal medulla. a-and .3-adrenergic receptor agonists have been shown to cause EADs or facilitate their induction both in vivo23 25 and in vitro. 24,26 Circulating catecholamines may have shifted the cycle length-EAD relation to shorter cycle lengths under in vivo conditions, thereby increasing the propensity of the heart to develop EADs.…”

Baroreflex Sensitivity Predicts the Induction of Ventricular Arrhythmias by Cesium Chloride in Rabbits

“…1 In animal experiments, intravenous cesium chloride (Cs) administration produces EADs in the ventricular monophasic action potentials (MAPs) and causes both prolongation of the QT interval and polymorphic ventricular tachycardias (PVTs) resembling torsade de pointes. [2][3][4][5][6][7] The electrocardiographic changes and ventricular arrhythmias induced by Cs are considered to represent an experimental animal model of the long QT syndrome. [2][3][4] Torsade de pointes associated with the long QT syndrome is often elicited by sudden increases in sympathetic activity 8 and can be suppressed by -adrenergic blocking agents 9 or by ablation of the left stellate ganglion.…”

“…[2][3][4][5][6][7] The electrocardiographic changes and ventricular arrhythmias induced by Cs are considered to represent an experimental animal model of the long QT syndrome. [2][3][4] Torsade de pointes associated with the long QT syndrome is often elicited by sudden increases in sympathetic activity 8 and can be suppressed by -adrenergic blocking agents 9 or by ablation of the left stellate ganglion. 10 Isoproterenol infusion prolongs the MAP duration and induces EADs in patients with long QT syndrome.…”

“…11 In addition, left stellate stimulation increases the amplitude of EADs induced by Cs and increases the occurrence of ventricular tachycardia (VT) in dogs. 3 Recently, Priori et al reported the differential responses to -adrenergic stimulation in a cellular model of long QT syndrome and suggested that vulnerability to catecholamines may differ in patients with long QT syndrome according to the gene involved. 12 We have shown that vagal stimulation decreases the amplitude of Cs-induced EADs and suppresses the development of PVT.…”

The ionic mechanism of reperfusion-induced early afterdepolarizations in feline left ventricular hypertrophy.

“…In 28 cats (wt 2.5-4.5 kg; mean 3.4±0.6 kg) of either sex, general anesthesia was induced with 5% isoflurane and 02 flowing at 1 liter/ min using an isoflurane-specific vaporizer ( Using standard sterile techniques, the abdomen was entered through a midline incision, the abdominal aorta was dissected, and a nonabsorbable polytetrafluoroethylene-coated polyester tie (0 Ethiflex) was looped around the aorta just cranial to the renal arteries. A tie was made to constrict the aorta to -10% ofthe original surface diameter; this usually increased systolic blood pressure in the right brachial artery, monitored during general anesthesia, by [20][21][22][23][24][25][26][27][28][29][30] 50 ,M Ca2". Enzymatic perfusion was continued until the solution flowed freely ( 12-15 min).…”