Role Of Toll-like Receptor 4 In The Pathogenesis Of Dilated Cardiomyopathy In Children And Efficacy Of Carvedilol

Objective To observe the expression of Toll-like receptor 4(TLR4)in peripheral blood monocytes and the concentration of Tumor necrosis factor-α(TNF-α) in serum of children with dilated cardiomyopathy (DCM ), for preliminarily study the role of TLR4 and TNF-αin the pathogenesis of DCM in children ,in order to explore the relationship between TLR4 and TNF-αthat participating in the occurrence and development of children with DCM.To investigate the efficacy,safety and tolerance of carvedilol for DCM in children.Methods 18 children with DCM, TLR4 level in monocytes was measured by flow cytometry; the concentration of TNF-αin serum was determined by ELISA;left ventricular ejection fraction(LVEF), Left ventricular fractional shortening(LVFS), left ventricular end-diastolic volume(LVEDV), left ventricular end-systolic volume(LVESV) and left ventricular mass(LVmass) were detected by echocardiography. 17 healthy children served as controls.After definite diagnosis,children with dilated cardiomyopathy were given regular treatment of digoxin,enalapril,spironolactone,carvedilol. Improvement of cardiac function,safety and tolerance in patients were given after treatment of carvedilol or metoprolol that were observed and compared with each other.Results The mean fluorescence intensity( MFI )of TLR4 in monocytes was higher in children with DCM at preliminary diagnosis,compared with that of treatment of one year . Also TNF-αhad a similar result(P<0.05).Moreover,they were both higher in chidren with DCM contrast to controls(P<0.05). Positive correlation was observed between TLR4 and TNF-α(P<0.05). Negative correlation was observed between TLR4,TNF-αand LVEF(P<0.05).The improvement of LVEF, LVEDV, LVESV, LVmass in children with DCM correlated with the decrease of TLR4MFI and with the concentration of TNF-α. Improvement of cardiac function was no significant difference between metoprolol group and carvedilol group. LVEDV, LVESV, LVmass significantly decreased in carvedilol group between pre-therapy and post-therapy.LVESV significantly decreased in metoprolol group between pre-therapy and post-therapy. The decrease of LVEDV, LVmass were no significant difference between pre-therapy and post-therapy. Carvedilol group was significantly higher than metoprolol group to the percentage of the maximum tolerated dose of drug. in reversing of ventricular remodeling and tolerance.There were no apparent adverse reactions. Conclusions Upregulation of TLR4 in monocytes of children with DCM may play a critical role in the mechanism of cardiac damage through the secretion of inflammatory factors,which mediate the development and progression of children with DCM. Carvedilol can improve ventricular systolic function and reverse left ventricular remodeling,with good tolerability and safety in children with DCM. And carvedilol is better than metoprolol in reversing of ventricular remodeling and tolerance.