| Objective:To investigate the effects of ivabradine on ventricular arrhythmias susceptibility in myocardial infarction Rats.Methods: A total of 60 male Sprague Dawlry(SD)rats were randomly divided into 5 groups.(1)MI Group: myocardial infarction(MI)model was established by coronary artery left anterior descending(LAD)ligation and the group was fed a normal diet for 4 weeks.(2)IVA Group: MI model was established and the group was given IVA 10mg/(kg·d)by gavage for 4 weeks.(3)MET Group: MI model was established and the group was given MET 50mg/(kg·d)by gavage for 4 weeks.(4)IVA+MET Group: MI model was established and the group was given IVA 10mg/(kg·d)and MET 50mg/(kg·d)by gavage for 4 weeks.(5)the Sham-operated Group: the model was established by thread but not ligation of coronary artery and group the fed a normal diet for 4 weeks.After 4 weeks,all survived rats were recorded weight?heart rate and blood pressure.The ventricular electrical parameters were detected by burst pacing using multi-channels cardiac electrophysiological polygraph,including the QRS duration and Q-T interval duration,ventricular effective refractory period(VERP),VERP dispersion,inducibility and lethality of ventricular tachycardia(VT)and ventricular fibrillation(VF).The myocardial interstitial collagen volume fraction and morphological characteristics were respectively evaluated by Masson' trichrome staining and HE staining respectively.P-Cx43 and t-Cx43 in the left ventricle anterior wall were detected by immunohistochemistry.Western blot was performed to analyze p-Cx43?t-Cx43.Results: heart rate examination showed that: Compared with the Sham group,MI group had no significant differences in heart rate(P > 0.05);Compared with the MI group,heart rate of IVA group,MET group and IVA + MET group were slowed significantly(all P < 0.01);Compared with the group MET,IVA group had no significant differences in heart rate(P > 0.05),heart rate of IVA + MET group was slowed(P < 0.01).Blood pressure measurement results: the preoperative and 4 weeks postoperative,there was no significant difference in blood pressure of 5 groups(P>0.05).Electrophysiological examination showed that: QRS-wave had no significant differences among 5 groups(P>0.05).Compared with Sham group,QT and QTc interval duration in MI group were obviously prolonged,VERP was significantly shorten,inducibility and lethality of VT/VF were significantly increased(all P<0.01);Compared with MI group,QT and QTc interval duration VERP,VERPd in IVA group,MET group and IVA + MET group was shorten(all P < 0.01),inducibility and lethality of VT/VF in IVA group,MET group were decreased(all P < 0.05),inducibility and lethality of VT/VF in IVA +MET group were decreased(respectively p< 0.01 and 0.05);Compared with MET group,QT and QTc interval duration in IVA + MET group were shorten,VERP,VERPd and inducibility of VT/VF were decreased(all P < 0.05);lethality of VT/VF in IVA+ MET group had no significant difference(P >0.05);there was no significant difference between IVA group and MET group(all P > 0.05).The histological examination and Masson' trichrome stain showed that patchy myocardial ischemia,necrosis with inflammatory cells infiltration and obviously ventricular interstitial fibrosis in MI group.Compared with the Sham group,left ventricular infarction area and ventricular interstitial fibrosis of MI group were obviously increased(all P<0.01);Compared with MI group,left ventricular infarction area and ventricular interstitial fibrosis of IVA group,MET group and IVA + MET group were obviously decreased(all P < 0.01);Compared with group MET,left ventricular infarction area and ventricular interstitial fibrosis of IVA group had no significant differences(P > 0.05),left ventricular infarction area and ventricular interstitial fibrosis of IVA + MET group were decreased(P Respectively < 0.05 and 0.01).Immunohistochemistry and Western blot revealed both demonstrated t-Cx43 had no significant differences among five groups(all P>0.05).Compared with Sham group,p-Cx43 expression of MI group was reduced(P < 0.01);compared with MI group,p-Cx43 expression was increased in IVA group,MET group and IVA + MET group(all P<0.01);compared with MET group,p-Cx43 expression in IVA group had no significant differences(P>0.05),p-Cx43 expression was increased in IVA + MET group(P Respectively < 0.01 and 0.05).And immunohistochemistry revealed:in ventricular cells of Sham group,t-Cx43 and p-Cx43 were almost istributed in cardiac intercalated disk,while which were redistributed at the lateral surface in MI group.T-Cx43 and p-Cx43 distribution of IVA group,MET group and IVA + MET group between Sham group and MI group.Conclusions: IVA may slow heart rate and reduce the infarction area of myocardial fibrosis and infarction area,improve the expression and redistribution of p-Cx43 in myocardial infarction area,may improve left ventricular myocyte remodeling and electrical remodeling after myocardial infarction in rats,thereby reducing the susceptibility of ventricular arrhythmia after myocardial infarction.The combination of IVA and MET was better. |
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