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Background Postconditioning has been shown to reduce infarct size, ischemic/reperfusion injury and myocardial injury in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). This study tested the hypothesis that postconditioning attenuates the elevation of tumor necrosis factor-α (TNF-α) and improves heart function in patients with AMI after PCI.Methods A total of 75 patients were randomly assigned to 1 of 3 groups: the routine group (n=26), in which no intervention was given at the onset of reperfusion; and the Postcon-30s (n=25) or Postcon-60 s (n=24) groups, in which 3 cycles of 30- or 60-second balloon deflation and inflation were repetitively performed. TNF-α serum concentration was measured by ELISA. Global and regional left ventricular systolic function was determined by echocardiography at 1 year.Thirty-four normal controls (NC) were enrolled in the study.Results The TNF-α concentration in patients with AMI was significantly elevated at baseline compared to controls (P <0.01). Concentration levels increased in the routine and Postcon-30s, but not in Postcon-60s group at 7 days (P <0.05).As for linear associations among the three groups, left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) were ranked as follows: Postcon-60s >Postcon-30s>routine (P values all <0.05, 65% vs. 57% vs. 52% and 1.10 vs. 1.27 vs. 1.53) after 1 year. More importantly, there was a significant relevance between the soluble TNF-α serum concentration at 7 days and LVEF or WMSI after 1 year (P values all <0.0001).Conclusions Postconditioning, in particular Postcon-60s was associated with long-term cardioprotective effects for inhibition of the inflammatory response and reperfusion injury. The soluble TNF-α serum concentration provided powerful prognostic information of global and regional left ventricular systolic function in patients with AMI.