The Effect Of Beta-adrenergic Blockers On The Early Myocardial Damage In Septic Rats

Objective To construct septic rat model , observing the level of cTnI,TNF-αin serum and SOD,MDA,NF-κBp65,apoptosis index in heart tissue. To investigate the interventional effect and it's possible mechanism of beta-adrenergic blockers(Propranolol—non-selective beta-adrenergic blocker and metoprolol—β1-selective beta-adrenergic blocker)on the early myocardial damage in septic rats,and provide experimental evidence for clinic prevention and treatment of sepsis-induced myocardial damage.Methods 96 male Sprague-Dawley(260-300g) rats were randomly divided into 4 groups: the sham group(n=24), the cecal ligation and puncture group(sepsis group, n=24), the propranolol group(n=24), the metoprolol group(n=24) . Cecal ligation and puncture(CLP) was adopted to reproduce animal model of sepsis in the 3 latter groups. Sham-operated animals (controls) underwent identical laparotomy but without cecum ligation and puncture. The contents of serum cTnI and TNF-αwere detected in each group at 3,6,12,24 hours after the operation ,as well as activities of SOD and MDA in myocardium which was obtained from the left ventricle. The changes of myocardial pathomorphology by HE and myocardial cells apoptosis by TUNEL were observed through the microscope. The expression of NF-κBp65 in myocardium was determined by P-V immunohistochemistry.The myocardial cells apoptosis was detected by confocal microscopy.Results 1.The level of serum cTnI and TNF-αin sepsis group was much higher than that in sham group at each point time after cecal ligation and puncture(P<0.05).At the same time,the activity of MDA in myocardium in sepsis group was much higher than that in sham group(P<0.05),but the activities of SOD was much lower(P<0.05).The expression of NF-κBp65 and the apoptosis index of myocardial increased significantly in each time as compared with sham group(P<0.05).2.In the treatment groups,the indexes above-mentioned were lower than sepsis group(P<0.05), except that activity of SOD was higher(P<0.05).3.The level of SOD in propranolol group was much higher than that in metoprolol group at each point time after cecal ligation and puncture(P<0.05),but the level of MDA was much lower(P<0.05).4.More myocardial cells boundary unsharpary, vacuolar degeneration and wave-like changes, intercellular substance edema and capillary engorgement were seen at 6,12h after the injury in sepsis group. Local myocardial cells necrosis and inflammatory cells infiltration were also observed and the pathological damage was aggravated at this time. Myocardial damage was improved at 24 hours after cecal ligation and puncture,then intercellular substance edema and capillary engorgement were also alleviated. The changes in the treatment group were alleviated than those in sepsis group after the injury.Conclusions The cardiac myocytes damage occurs early following the sepsis and is continuing,beta-adrenergic blockers of metoprolo and propranolol also might protect myocardium from the damage resulted from sepsis in a rat model,probably by lowering expressions of TNF-α,NF-κB_P65,myocardial apoptosis and depressing activity of sympathetic nervous. In addition , extra cardioprotection of both may be also associated with antioxidant effects. Propranolol(non-selective beta-adrenergic blocker) has a better protective effect on antioxidation than metoprolol(β1-selective beta-adrenergic blocker).