Effects Of Gap Junction Modifier On Myocardial Electrophysiological Properties Changes Caused By Dexmedetomidine And Its Mechanism

Objective:To observe the effect of gap junction modifier on electrophysiological changes induced by dexmedetomidine and its possible mechanism.Methods:Eighteen healthy adult SD rats of either gender,weighing（300±30）g,were prepared isolated heart perfusion model by Langendorff.After 15min perfusion and balance of K-H fluid,the isolated hearts were randomly divided into 3 groups（n=6）:The hearts were continuously pefused for 30 min with 37℃K-H solution in control group（group C）,with dexmedetomidine 50 ng/ml in dexmedetomidine group（group D）,or with rotigaptide 80 nmol/L combined with dexmedetomidine 50 ng/ml in rotigaptide combined with dexmedetomidine group（group ZD）.At the end of equilibration balanced infusion for 15 min（T₀）and at 15min（T₁）,30 min（T₂）of continued perfusion,the heart rate（HR）,endocardium and epicardium monophasic action potential（MAP）were recorded,50%monophasic action potential duration(MAPD₅₀),90%monophasic action potential duration(MAPD₉₀),monophasic action potential amplitude（MAPA）and maximal velocity（Vmax）were calculated.After perfusion for 30 min,using program-controlled stimulation and S1S1-increasing electrical stimulation,the ventricular effective refractory period（VERP）and the earliest pacing cycle length of the ventricular arrhythmia（VA-PCLmax）and the occurrence of VA were recorded.the ratio of VERP to MAPD₉₀(VERP/MAPD₉₀)were calculated.After the experiment,left ventricular myocardium were collected and the expression of connexin43（Cx43）protein was detected by western blot and immunohistochemistry.Results:Compared with T₀,HR in group D was significantly declined at T₁,T₂,group D showed slower HR than group C and ZD（P<0.05）,there was no significant difference in HR between group C and group ZD（P>0.05）.Compared with T₀,MAPD₉₀0 and MAPD₅₀0 in group D were significantly increased at T₁,T₂（P<0.05）,MAPD₉₀0 and MAPD₅₀0 in group D showed longer than group C and ZD,there was no significant difference in MAPD₅₀0 and MAPD₉₀0 between group C and group ZD（P>0.05）.there was no significant difference in MAPA and Vmax among the three groups（P>0.05）.Compared with group C,VERP were significantly prolonged（P<0.05）,VERP/MAPD₉₀0 ratio was decreased（P<0.05）,VA-PCLmax was prolonged（P<0.05）,the incidence of VA was increased in group D（P<0.05）.Compared with group D,VERP were significantly shortened（P<0.05）,VERP/MAPD₉₀0 ratio was increased（P<0.05）,VA-PCLmax was shortened（P<0.05）,the incidence of VA was decreased in group ZD（P<0.05）.Compared with group C,VERP were shortened（P<0.05）and there was no significant difference in VERP/MAPD₉₀0 ratio,VA-PCLmax and the incidence of VA（P>0.05）in group ZD.Biochemical indicators showed that,compared with group C,the expression of Cx43 in group D was downregulated and the proportion of end-end connection declined（P<0.05）,compared with group D,the expression of Cx43upregulated and the proportion of end-end connection increased in group ZD（P<0.05）,there was no significant difference in Cx43 expression between group C and group ZD（P>0.05）.Conclusion:Gap junction modifier rotigaptide can reverse the electrophysiological changes caused by dexmedetomidine and by upregulating the expression of Cx43.