Effects of tumor necrosis factor-α on MAPD between endocardium and epicardium in isolated heart tissues and study for mechanism / 中国免疫学杂志

ABSTRACT

Objective: To explore the relationship between expression of tumor necrosis factor-α( TNF-α) and electrophysiological heterogeneity in isolated heart tissues and isolated rat ventricular myocytes.The arrhythmogenic mechanisms of TNF-αwere further studied.Methods:Langendorff perfused heart tissues models were used to verify the arrhythmogenic effects of TNF-α.The monophasic action potentials( MAPs) of the endocardium and epicardium from the isolated heart tissues were recorded by elec-trophysiological experiments.The isolated rat ventricular myocytes were obtained by enzymatic dissociation.K+currents(Ito,IK1)were recorded by using whole cell patch clamp technique.Results: Compared to the control group, the difference in MAPD between endocardium and epicardium dramatically increased with TNF-α( P<0.05 ) .TNF-αcould cause MAP duration ( MAPD ) prolongation, and a single dose of TNF-αdifferentially affected the MAPs of endocardium and epicardium of isolated heart tissues.Compared to the control group,the K+currents(Ito,IK1)were dose-dependently decreased with TNF-αin rat ventricular myocytes(P<0.05).However, etanercept had no effects on the MAPD in the absence of TNF-α.Conclusion:TNF-α-induced heterogeneity of MAPD between the endo-cardium and epicardium may provide the substrate for the onset of ventricular arrhythmias during acute myocardial infarction.The effect might be associated with TNF-αcontribute to re-entrant ventricular arrhythmias which resulted from decreased K+currents(Ito,IK1).