Study Of Mechanism Of Ventricular Arrhythmias In The Short QT Duration Syndrome

Objective:To study the mechanism of electrical instability of short QT syndrome modle induce by pinacid and the effect of gap junction agonist aap10 to the modle.Methods:To establish short QT syndrome modle by arterially perfuse pinacidil in rabbit left ventricular wedge preparations.20 New-Zealand rabbits were fell into pinacidil group and aap10 group randomly, every group 10 rabbits, the pinacidil group perfused 10μmol/L pinacidil and the aap10 group perfuse pinacidil 10μmol/L and aap10 500nmol/l mised liquor. Transmural ECG as well as action potentials from both endocardium and epicardium were simultaneously recorded. To observe the change of TDR (transmural dispersion of repolarization),QT interval and refractory period,and the induction of ventricular tachycardia (VT) or fibrillation (VF).Results:At a basic cycle length of 1000 ms, pinacidil (10mol/L) abbreviated the QT interval from291±19 ms To 232±19 ms (P＜0.05). The transmural dispersion of repolarization (TDR) decrease from 44±12ms to 22±7ms(P＜0.05), refractory period decrease from 164±8ms to 112±14ms (p<0.05)and stimulation applied to the endocardium induced a polymorphic VT (pVT) in 8 of 10 wedge preparations (P<0.05).there are no signally different in QT interval, TDR refractory period and the induce of VT after addition of aap10.Conclusions:The decrease of TDR and refractory period possible is the ventricular arrhythmia mechanism of the short QT interval modle estabished by pinacidil. AAP10 failed to rescue the electrical instability induced by pinacidil, indicating that TDR and gap junction may not involved or involved in a different pathway in the mechanisms of SQTS. and there are no signally influence in short QT interval modle established by pinacidl causee by aap10. Objective:To study the gap junction opener antiarrhythmic peptide 10 (AAP10) on the torsades de pointes (TdP) induced by Ibutilide under the condition of hypopotassemia and hypomagnesemia, and to investigate the mechanism of TdP induced by Ibutilde and try to find methods to prevent it.Method:Japanese long-eared white rabbits were divided into control group, hypopotassemia and hypomagnesemia group, Ibutilide group, Ibutilde and hypopotassemia and hypomagnesemia group and AAP 10 group. In control group, perfused with Tyrode's solution; in hypopotassemia and hypomagnesemia group, perfused with hypopotassemia and hypomagnesemia Tyrode's solution; in Ibutilde group, perfused with 2mg/l Ibutilde; in the Ibutilde and hypopotassemia and hypomagnesemia group,2mg/l Ibutilde was perfused under the conditon of hypopotassemia and hypomagnesemia; in AAP 10 group,500nmol/L AAP 10 was added to the Ibutilide under the condition of hypopotassemia and hypomagnesemia. The perfusion time in each group was 1 hour and 40 minutes. The early after depolarization (EAD), R on T extrasystole, TdP and the changed of QT interval, T wave peak to T wave end (Tp-e) and Tp-e/QT were observed.Result:Compared with control group, the incidence of EAD, R on T extrasystole, TdP increased and the QT interval, Tp-e and Tp-e/QT prolonged in the Ibutilide and hypopotassemia and hypomagnesemia group. In AAP 10 group, the incidence of TdP decreased and the QT interval, Tp-e and Tp-e/QT shortened compared with Ibutilide and hypopotassemia and hypomagnesemia group.Conclusion:The TdP induced by Ibutilde under the conditon of hypopotassemia and hypomagnesemia can be prevented by AAP 10. Objective To study the role of CaM kinaseⅡand protein kinase A signal transduction pathway in the Catecholaminergic polymorphic ventricular tachycardia (CPVT).Mehtods Japanese rabbits were randomly divided into control group, model group, KN93 group, and H89 group. Arterially perfused rabbit left ventricular wedge preparations were prepared. The control group ferfused with Tyrode's solution and the model group perfused with caffeine and isoproterenol to mime the CPVT. The KN93 group perfused with KN93 and caffeine and isoproterenol. H89 group perfused with H89 and caffeine and isoproterenol. The triggered activity (TA) and ventricular arrhythmias were observed after single string stimulation.Results The incidence of triggered activity and ventricular tachycardia in control group are 0. After perfused with caffeine and isoproterenol the QT interval were decreased. The incidence of triggered activity and ventricular tachycardia in model group are 12/13 and 8/13 respectively. After treating with KN93 and H89, the incidence of triggered activity decreased to 4/9 and 6/11 and the incidence of and ventricular tachycarida reduced to 1/9 and 2/11. Calmodulin kinaseⅡinhibitors and protein kinase A inhibitor can reduce the triggered activity and ventricular tachycardia in the drug mode.Conlusion CaM kinaseⅡand protein kinase A signal transduction pathway paly an important role in the catecholaminergic polymorphic ventricular tachycardia.