Protective Effect of Wenxin Granula on Heart from Myocardial Infarction through Regulating Intracellular Ca^(2+)

Objective To assess the anti-arrhythmic activity and cardioprotective effects of Wenxin Granula,a traditional Chinese formula(consisting of Salviae Miltiorrhizae Radix,Polygonati Rhizoma,Notoginseng Radix et Rhizoma,Nardostachyos Radix et Rhizoma,Angelicae Sinensis Radix,and Succinum),on heart in ischemic-induced myocardial infarction(MI) rats and compare with those of Amiodarone which have been demonstrated in clinic.Methods Rats were randomly divided into Sham-operated(control),MI + Amiodarone [5 mg/(kg.d)](MI),and MI + Wenxin Granula [10 mg/(kg.d)] groups and left anterior descending coronary artery was occluded in each group.After left anterior descending for 12 h,standard lead II of administration electrocardiogram was recorded in order to analyze the occurrence of arrhythmia.After one month,the size of the infarct area of heart was evaluated by TTC staining method and haemodynamic function was assessed to detect the heart function.Laser scanning confocal microscope and the technique of patch clamp were used to detect the intracellular Ca2+([Ca2+]i) and L-type calcium current(ICa-L),respectively.Results Both Wenxin Granula [10 mg/(kg.d)] and Amiodarone [5 mg/(kg.d)] could markedly decrease the incidence of arrhythmia in heart of rats which were subjected to ischemic injury.After one month,Wenxin Granula could significantly decrease mortality to 22.22% and reduce the infarct area(P < 0.05),but Amiodarone did not.The mechanism may involve that Wenxin Granula attenuated [Ca2+]i decreasing in MI rats.Additionally,Wenxin Granula could obviously ameliorate the impaired heart function of MI rats by decreasing the elevated left ventricular end-diastolic pressure and increasing the attenuated maximum change velocity of left ventricular pressure in the isovolumic contraction or relaxation period.On the other hand,electrophysiological experiment results revealed that Wenxin Granula administration one month later also increased the reduced ICa-L density in rat ventricular myocytes in MI rats.The results of LSCM showed that Wenxin Granula could recover the amplitude of [Ca2+]i decreased by heart failure during long term.Conclusion Wenxin Granula could not only inhibit the incidence of arrhythmia but also decrease the mortality,which was accompanied by recovering the amplitude of [Ca2+]i.This protective effect of Wenxin Granula may partially be mediated through changing ICa-L as well as increasing [Ca2+]i.