ABSTRACT
Objective To evaluate the effects of dexmedetomidine on action potential in isolated rabbit sinoatrial node cells.Methods Twenty-four healthy New Zealand rabbits of both sexes,weighing 1.5-2.5 kg,were sacrificed.Their hearts were removed and sinoatrial nodes were dissected and placed in Tyrode solution.Sixty isolated sinoatrial nodes were randomly divided into 6 groups (n =10 each):control group (group C),0.5 ng/ml dexmedetomedine group (group D1),5.0 ng/ml dexmedetomedine group (group D2),dexmedetomidine 5.0 ng/ml + yohimbine 1 μmol/L (alpha 2-adrenoreceptor antagonist) group (group D2 + Y),dexmedetomidine 5.0 ng/ml + 2 mmol/L CsCl (blocker of pacemaker current) group (group D2 + C),and dexmedetomidine 50.0 ng/ml group (group D3).After perfusion with the Tyrode' s solution for 60 min,C group was perfused with Tyrode' s solution for another 40 min,D1-3 groups were perfused with Tyrode's solution cont(a)ining dexmedetomedine 0.5,5.0 and 50.0 ng/ml,respectively,for40 min,and D2 + Y and D2 + C groups were perfused with Tyrode' s solution containing 1 μmol/L yohimbine and 2 mmol/L CsCl,respectively,for 20 min,and then 5.0 ng/ml dexmedetomedine was added and sinoatrial nodes were perfused for 20 min.Maximal rate of depolarization (Vmax),amplitude of action potential (APA),action potential duration at 50％ and 90％ repolarization (APDso and APD90),velocity of diastolic (phase 4) depolarization (VDD),and rate of pacemaker firing (RPF) were recorded at 60 min of perfusion with Tyrode' s solution (T1),20 min of perfusion with yohimbine or CsCl (T2) and termination of perfusion with dexmedetomedine (T3).Results Compared with group C,APA,VDD and RPF were gradually decreased at T2,3 in groups D1-3 (P ＜ 0.05),and there was no significant difference in Vmax,APD50 and APD9o among C and D1-3 groups (P ＞ 0.05).VDD and RPF at T2 in group D2 + C and APA,VDD and RPF at T3 in groups D2 + Y and D2 + C were significantly lower than those at T1 (P ＜ 0.05).APA,VDD and RPF in group D2 + Y and APA in group D2 + C were significantly lower at T3 than at T2 (P ＜ 0.05).Conclusion Dexmedetomidine can decrease the sinoatrial node autorhythmicity in a concentration-dependent manner in rabbits,and the mechanism may be related to the inhibition of pacemaker current,but not alpha 2-adrenoreceptor.