Relationship Between Oxidative, Nitrosative Stress And Myocardial Injury In Rats With Sepsis

Background Sepsis is part of a spectrum of conditions ranging from the systemic inflammatory response syndrome (SIRS) to septic shock and multiple organ dysfunction syndrome(MODS). Sepsis and its sequelae continue to be the main causes of morbidity and mortality in the intensive care unit. In America the average costs per case was $22,100 with annual total costs of $16.7 billion nationally. Several mechanisms of inflammation and organ damage have been implicated in the pathogenesis of sepsis, and the pathogenesis of cardic dysfunction is still unclear.Objection To investigate the pathological changes and alterations of parameters associated with oxidative and nitrosative stress in myocardium of rats with sepsis.Methods Thirty-eight Wistar rats were randomly allocated into cecal ligation and puncture (CLP) group to establish animal model of sepsis (n=19) or sham procedure control group (n=13) . 24 hours later, pathologic changes in heart tissues of all animals were observed. Serum concentrations of myocardial enzyme and cardiac superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), nitric oxide(NO), induced nitric oxide synthase (iNOS) and total nitric oxide synthase(NOS) were detected in both group of rats, the eliminating capability of superoxide anion (O₂·^- ) by SOD and hydroxyl radicals (OH) by peroxidase in the heart tissue were also measured.Results The pathologic changes of heart tissue in septic rats included edema, congestion in mesenchyma and inflammatory cells infiltration, no pathological damage was seen in sham controls. In comparison with controls, there was a significant increase in serum concentration of myocardial enzyme in septic rats 24 hours post-operation: CK( 1745.3 ± 254.5 vs 201.6 ± 15.5 U/L, P<0.01), CK-MB( 1132.2 ± 201.4 vs 91.2 ± 11.0 U/L, P<0.01 ), and multiple parameters of cardiac oxidative and nitrosative stress were also increased significantly: SOD(225.7 ± 31.7 vs 166.2 ± 8.3 U/mgprot, P<0.01 ), the eliminating capability of O₂·^- ( 766.1 ± 93.1 vs 637.2 ± 53.4 U/gprot, P<0.01 ), MDA( 10.4 ± 4.2 vs 5.9 ± 1.8 nmol/mgprot, P<0.01 ), GSH-PX( 71.0 ± 10.1 vs 58.9 ± 10.4 U/mgprot, P<0.01 ), NO( 2.9 ± 0.4 vs 0.8 ±0.1 μmol/gprot, P<0.01 ), iNOS( 2.8 ± 0.6 vs 0.5 ± 0.1 U/mgprot, P<0.01 ) and NOS( 3.5 ± 0.6 vs 0.9 ±0.1 U/mgprot, P<0.01), while the eliminating capability of OH· by peroxidase had no obvious change( 630.1 ± 81.8 vs 628.9 ± 80.0 U/gprot, P > 0.05).Conclusion: Oxidative and nitrosative stress involves in the pathogenesis of the myocardial injury in sepsis.