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Effects of Adenosine A1-receptor activation on Torsade de Pointes in Rabbits

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Abstract

Purpose: We tested whether the adenosine A1 receptor agonist, R-PIA, suppressed torsade de pointes (TdP) induced by the delayed rectifier potassium channel blocker clofilium. Furthermore, we studied the underlying mechanism: β-adrenergic antagonism or ATP-sensitive K+ channel (IK-ATP) opening. Methods: In anesthetized rabbits, TdP was induced by simultaneous infusion of clofilium and the α1-adrenoceptor agonist methoxamine. Four groups were studied: (1) saline infusion after TdP induction; (2) R-PIA (1.3 mg/kg) infusion; (3) R-PIA infusion after propranolol (2 µmol/kg) pretreatment; (4) R-PIA infusion after glibenclamide (10 µmol/kg) pretreatment. Results: TdP suppression rate was 0% in group 1, 78% in group 2 (p < 0.01 vs group 1), 67% in group 3 (p < 0.05 vs group 1, p = NS vs group 2), 33% in group 4 (p = NS vs group 1, p = 0.08 vs group 2). TdP induction coincided with increased QT/QTc duration and QT dispersion. TdP suppression coincided with reduced QT dispersion, but further QT/QTc lengthening. Conclusions: R-PIA suppressed TdP, not by β-adrenergic antagonism, but mostly by IK-ATP opening. QT dispersion correlated better with TdP induction/suppression than QT/QTc duration.

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  1. Cardiac Electrophysiology and Arrhythmia Service, Stanford University Medical Center, Stanford, California, USA

    Hanno L. Tan, Charles J. Y. Hou & Ruey J. Sung

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  2. Charles J. Y. Hou
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Tan, H.L., Hou, C.J.Y. & Sung, R.J. Effects of Adenosine A1-receptor activation on Torsade de Pointes in Rabbits. Cardiovasc Drugs Ther 13, 441–447 (1999). https://doi.org/10.1023/A:1007812224862

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