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Background and Objective Increased transmural dispersion of repolarization (TDR) has been shown to contribute toinitiation and maintenance of ventricular arrhythmia in long QT syndromes(LQTS).Intercellular uncoupling through gap junctions isan important mechanism for maintaining TDR in both intact and diseased heart.The present study was to test the hypothesis thatimproving gap junction communication reduces TDR and prevents ventricular arrhythmia in rabbit LQT2 model.Methods Anarterially perfused rabbit left ventricular preparation and E-403 (0.5μmol/L)were used to establish a model of LQT2.Preparationswere randomly assigned to control(n=10),AAP-100nmol/L(n=10),AAP-500nM(n=10)groups.Transmural ECG as well as actionpotentials from both endocardium and epieardium was simultaneously recorded. Resuits In LQT2 model.presence of 500nmol/LAAP10 reduced endocardial action potential and TDR and prevented ventricular arrhythmia comparing with the control and AAP 100nmol/Lgroups(P＜0.05).Conclusions The presence of 500 nmol/LAAP10 reduces TDR and prevents ventricular arrhythmia in rabbitventricular model of LOT2.This study suggests a possible role of GJs in TDR in rabbit LQT2 model and indicates a new clinicalapproach to the management of LQTS.
RESUMEN
In order to confirm the hypothesis that during acute hypoxia, the antiarrhythmic peptide (AAP10) could improve conductance by changing the phosphorylation state of connexin43 (Cx43),isolated perfused rat hearts were randomly divided into three groups: control, hypoxia and AAP10 (n=9 in each group). The change in Cx43 phosphorylation was tested by Western-blot; the distribution of Cx43 was observed by confocal immunofluorescence microscopy. Western-blot analysis revealed that the expression of total Cx43 protein was significantly decreased during acute hypoxia,while nonphosphorylated Cx43 (NP-Cx43) was unchanged. AAP10 could increase the expression of total Cx43 protein, but had no effects on the NP-Cx43 protein. Immunofluorescence study showed that during acute hypoxia, both total Cx43 and NP-Cx43 proteins were greatly decreased, while AAP10 only increased the expression of total Cx43 protein, but had no effect of the NP-Cx43 protein expression. These findings suggested that the decrease of intercellular communication may be associated with the reduction of phosphorylated Cx43 (p-Cx43) and translocation of NP-Cx43 from the surface of gap junction into intracellular pools during acute hypoxia. AAP10 can improve intercelluar communication by enhancing phosphorylation of Cx43.