The Therapeutic Effect And The Mechanism Of Ribavirin To Viral Myocarditis: Experimental Research

Background and Objectives:Viral myocarditis (VM) is one of the common acquired cardiovascular diseases in children.VM could be caused by more than 20 kinds of viruses.Coxsackie virus B(CVB) is the most frequent cause of VM,and is responsible for more than half patients with VM. Its pathological characteristics are focal or diffuse infiltrates of mononuclear cells.The morbidity of VM is increasing recently.Most of patients with viral myocarditis could be recovery completely with normal cardiac function. A few of them improve clinically but show residual cardiac dysfunction, and a few of them have cardiac enlargement, chronic heart failure and die or require heart transplantation.The mechanism of VM is not very clear till now,and it is generally thought that the mechanism include the direct invasion of virus to myocardium,production of myocardial toxin,and the immunologically abnormality(virus induced immunity and autoimmnity). Therefore,the treatment of VM focus on both anti-virus and preventing the cardiac myocyte from damage by immunologically abnormality,but there are short of special and effective control.In this study ,we employed a model of VM using Balb/c mice inoculated with CVB₃,then give the treatment of ribavirin in order to investigate the therapeutic effect and the mechanism.Materials and Methods:120 4-week-old Balb/c male mice were randomly divided into 3 groups,40/group,including:normal control(A),viral control(B),ribavirintreatment(C),each mouse in group B and C was inoculated with 0.2ml CVB3 (TCID50 1075/ml) intraperitoneally , while group A mice were given 0.2ml normal saline.Group C mice were treated by ribavirin,and group A and B were simply given normal saline in the same way.10 mice of each group were killed on day 7, 14, 21 after inoculation. Blood was obtained by eye-ball excision ,and their hearts were removed sterility and observed:1 .Histopathologic examination of the heart by optical microscope, myocardial histopathologic scores were counted,and myocardial ultrastructure were observed by transmission electron microscopy.2.Viral titer in myocardium was detected with PFU method.3.The level of serum cardiac troponin I(cTnl) was measured quantitatively by using chemiluminescence method.4.Serum anticardiolipid antibody IgG (ACA-IgG) was detected quantitatively by enzyme-linked immunoadsorbent assay(ELISA) method.5.T cell subset (CD4> CDg)in peripheral blood were quantitatively detected by using flow cytometry. Results:1 .Pathological changes of myocardium : There were no pathological changes in myocardium in group A , and the incidence of myocarditis was 100% in group B and C. However, the mortality and the pathological changes were different in each group : the mortalities were 25% and 17.5% in group B and C.In group B ,the pathological damage of myocardium was significant on day 7,and reached the peak on day 14.In group C,the pathological damage was reduced to some extent.2.The change of viral titer in myocardium : the amount of viral titer was 0 in myocardium of group A ,however,it reached the peak on day 7 after inoculated CVB3 in group B and C,and thereafter gradually decreased . Viral titer was lower in group C than in group B,and it was positively related with the pathological scores on day7(r=0.64 P <0.05),no relativity on day 14.3.The level of serum troponin I(cTnI):the amount of cTnl was minute in serum of group A,and it increased significantly on day 7 after inoculated CVB3 in group B and C,reached maximum on day 14,then gradually decreased.The expression of cTnl was positively related with myocardium pathological scores(r=0.70 P (O.Ol).The level of cTnl in group C was lower than in group B.4.The level of serum anticardiolipid antibody IgG(ACA-IgG) and T cell subset (CD^ CDg)in peripheral blood :the level of ACA-IgG was higher in group B and C than in group A.However,T cell subset were lower;After the treatment of ribavirin ,the level of ACA-IgG decreased signi- ficantly. Conclusions:1.There were prominent changes in myocardium of VM mice:myocardium was damaged significantly.Viral titer,cTnI and ACA-IgG were increased significantly,and were positively related with the pathological scores. T cell subset (CD<^ CDg)in peripheral blood were significantly decreased.2.Ribavirin could improve the pathological changes of myocardium in VM mice,and decrease the mortality ,the viral titer and the level of serum cTnI,thereby ribavirin has good therapeutic effect to viral myocarditis and the mechanism is to decrease the viral titer in myocardium.3.Treating VM with ribavirin could decrease the serum ACA-IgG BI,but could not increase the level of CD^ CD8 .From this ,it shows ribavirin can modulate the humoral immunity.