901-65 Adenosine A1Receptor Activation Suppresses Torsade De Pointes by Opening ATP Sensitive K+ Channels in Rabbits

BackgroundTorsade de pointes (TDP) is thought to result from early afterdepolarizations (EADs). Although it has been shown that adenosine can suppress catecholamine-induced EADs in isolated guinea pig ventricular myocytes, its effects on TDP in vivoare uncertain.MethodsTDP was induced in 25 anesthetized rabbits weighing 3-4 kg by simultaneous intravenous infusion of methoxamine, an α1-adrenoceptor agonist (70 nmol/kg/minl, and clofilium, a blocker of the delayed rectifier K+channel (76 nmol/kg/minl. AfterTDP was initiated, saline (n=6) orthe adenosine Alreceptor agonist R-phenylisopropyladenosine (R-PIA, 1.3 mg/kg, n=61 was infused. Two additional groups were pretreated with propranolol (2 /-Lmol/kg, n=7), aβ-adrenoceptor blocker, or glibenclamide (10μmol/kg, n=6). an ATP sensitive K+ channel (IK-ATP) blocker. prior to R-PIA infusion.Suppression of TOPsalineR-PIAR-PIA/propranololR-PIA/glibenclamide0/65/6*6/7*2/6*p<0,05 vs salineResultsSuppression of TDP in the R-PIA and the R-PIA/propranolol groups was not associated with shortening of the QT interval (baseline: 205±9 ms, onset of TDP: 344±10 ms, after suppression of TDP: 400±40 ms [p<NS vs onset of TDP). mean±SD). but with reduction of QT interval dispersion (2.7±0,5%,7,5±1,1%, and 4.2 ±0,7% [p<0.05 vs onset of TDP], respectively). as measured from 6 limb leads.ConclusionAdenosine A1receptor activation suppresses TDP induced by K+channel blockade primarily by opening IK-ATP, rather than byantagonizing β-adrenoceptor mediated mechanisms. This effect is associated with reduced QT interval dispersion, but not with QT interval shortening