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Effects of adenosine A1-receptor activation on torsade de pointes in rabbits
1Cardiac Electrophysiology and Arrhythmia Service, Stanford University Medical Center, California 94305, USA.
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: beta-adrenergic antagonism or ATP-sensitive K+ channel (IK-ATP) opening.
Methods:
In anesthetized rabbits, TdP was induced by simultaneous infusion of clofilium and the alpha1-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 micromol/kg) pretreatment; (4) R-PIA infusion after glibenclamide (10 micromol/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 beta-adrenergic antagonism, but mostly by IK-ATP opening. QT dispersion correlated better with TdP induction/suppression than QT/QTc duration.