Preliminary Study On Cardiac Structure And Function And Electrocardiogram Of DSG2-F536C Transgenic Mice

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Assess the impact of DSG2-F536C mutation on cardiac structure and function by echocardiographyBackground:DSG2-F531C mutation was found in an arrhythmogenic right ventricular cardiomyopathy(ARVC)family,then we built the DSG2-F531C transgenic mice.Myocardial fibrosis and fatty were observed by pathology study which indicated that the mutation was pathogenic,but the detailed cardiac structure and function changes of DSG2-F536C transgenic mice still need further research.Aim:The study aimed to comprehensive assess ventricular structure and function of DSG2-F536C transgenic mice aged 10 weeks by echocardiography.Method:The experiment included three groups:WT group(C57BL/6J mice),HT group,HM group.Each group included 8 mice(aged 10 weeks).Echocardiography was used to investigate the changes of cardiac structure and function among the mice.Result:All of the mice were studied by cardiac ultrasound.The results showed that:(1)Compared with WT mice,the left ventricular ejection fraction(LVEF)of HT and HM mice declined significantly(HT group vs WT group,44.4±6.6%vs 57.5±3.8%,P<0.01;HM group vs WT group,36.3±6.7%vs 57.5±3.8%,P<0.01),while the HM mice showed a further decrease compared with HT mice(36.3±6.7%vs 44.4±6.6%,P<0.05).(2)Compared with WT mice,the left ventricular shorting fraction(LVFS)of HT and HM mice declined significantly(HT group vs WT group,21.8±3.7%vs 29.7±2.6%,P<0.01;HM goup vs WT group,17.1±3.3%vs 29.7±2.6%,P<0.01),while the HM mice showed a further decrease compared with HT mice(17.1±3.3%vs 21.8±3.7%,P<0.01).(3)Compared with WT mice,the Left Ventricular Internal Diameter at end Systole(LVIDs)and the Left Ventricular Internal Diameter at end Diastolic(LVIDd)of HT mice increased significantly(LVIDs:3.2±0.19mm vs 2.6±0.19mm,P<0.01;LVIDd:4.1±0.14mm vs 3.7±0.23mm,P<0.05),the LVIDs and LVIDd of HM mice increased similarly but with no statistic difference,and there were no significant difference between HM mice and HT mice.(4)Compared with WT mice,the Left Ventricular Posterior Wall thickness at end Systole(LVPWs)of HT and HM mice both became thinning(HT group vs WT group,1.0±0.11mm vs 1.210.15mm,P<0.01;HM group vs WT group,0.95±0.15mm vs 1.2±0.15mm,P<0.01),but there was no significant difference between HT mice and HM mice;(5)Compared with WT mice,the Interventricular Septal at end Systole(IVSs)of HM mice declined significantly(0,93±0.1mm vs 1.1±0.1mm,P<0.01),and no significant difference was found between HT mice and WT mice.(6)Compared with WT mice,the Right Ventricular Internal Diameter at end Diastolic(RVIDd)of HT and HM mice both increased,but with no significant difference(HT group vs WT group,0.48±0.32mm vs 0.31±0.23mm,P>0.05;HM group vs WT group,1.1±0.86mm vs 0.31±0.23mm,P>0.05).Conclusion:DSG2-F531C Transgenic mice at 10 weeks showed a declined left ventricular systolic function,an increased left ventricular internal diameter at end systole and diastolic,the left ventricular posterior wall thickness and the interventricular septal thickness both became thinning.Part? The study of electrocardiology in DSG2-F536C transgenic miceBackground:The changes of cardiac structure and function in mice were caused by DSG2-F536C mutation.Pathological examination showed significant fibrosis,calcification and fatty in right ventricular,accompanied with low expression of connex43(Cx43)and sodium ion channel.These changes might lead to electrocardiology abnormity including declined unipolar/bipolar voltage of local myocardium,decreased conduction,increased ventricular arrhythmia induced by reentry and triggered activity,and sudden death due to serious ventricular arrhythmia.Aim:The aim of this study was to observe the ECG parameters,the arrhythmia occurrence before and after drug,and the epicardial voltage changes of left and right ventricular of DSG2-F536C mutant mice,assess the impact of DSG2-F536C mutation on the ventricular arrhythmia susceptibility of the mice.Method:DSG2-F536C mutation transgenic mice were generated and divided into three groups:WT group,HT group and HM group,all of the mice aged 10 weeks.The heart rate,PR interval,QRS duration and QT interval were recorded,meanwhile,the occurrence of PVC and VT were observed before and after the administration with epinephrine.Finally,we opened the chest,then recording the epicardia unipolar voltage by epicardia mapping.Results:(1)The heart rate of HM was faster than WT and HT groups(HM group vs WT group,436.3±25.4bpm vs 358.7±30bpm,P<0.01;HM group vs HT group,436.3±25.4bpm vs 366.3±49.4bpm,P<0.05),and no significant difference was observed between HT mice and WT mice.The QRS wave duration of HM group was much longer than the other two groups(HM group vs WT group,12.3±1.2ms vs 11.2±0.4ms,P<0.05;HM group vs HT group,12.3ms±1.2 vs 10.6±0.5ms,P<0.01),and no significant difference was observed between HT mice and WT mice.The PR interval and QT interval of transgenic mice were longer than WT mice,but with no significant difference.(2)Before and after the administration of epinephrine,PVC and VT were absent in WT and HT groups.PVC and VT were found in one mouse of HM group before the administration with epinephrine,and after administration with epinephrine,PVC and VT were found in two HM mice.(3)The right ventricle unipolar voltage of HM was lower than the other two groups(HM group vs WT group,0.684±0.33mv vs 1.66±0.37mv,P<0.01;HM group vs HT group,0.684±0.33mv vs 1.48±0.35mv,P<0.01),and no significant difference was observed between HT mice and WT mice;Compared with WT mice,the left ventricle unipolar voltage of HT and HM mice tended to decrease,but with no significant difference(HM group:1.72±0.37mv,HT group:1.94±0.45mv,WT group:2.0±0.54mv).Conclusion:The heart rate increased,which indicating the exciting of sympathetic nerve,and the QRS wave duration prolonged were found in transgenic mice aged lOweeks.The ventricular arrhythmia increased before and after the administration with epinephrine and the reduction of right ventricular epicardia voltage were found in transgenic mice which indicating that the gene mutation increased the ventricular arrhythmia susceptibility of the mice.