Protective Effects Of Esmolol On Myocardium In Rats With Sepsis

ObjectiveTo explore the protective effects of esmolol on myocardium in rats of sepsis and to observe the influence of esmolol on seven-day survival rate in rats of sepsis.Then to study on dynamic change of catecholamine in serum of septic rats over time and to clarify the characteristics of catecholamine level in progression of sepsis and the protective mechanisms of esmolol.MethodsRats were treated with Cecal ligation and puncture(CLP) to evoke peritonitis to establish sepsis model,and all rats were given the internal jugular central venus catheterization on the left side.Seventy two male Sprague-Dawley rats(250 ~300g)were randomly allocated to three groups:the Sham operation group(Sham group,n=24),the Cecal ligation and puncture group(NS group,n=24),the esmolol group(ES group,n=24).Six rats were randomly selected from each group to do the seven-day survival analysis and then the remaining rats of each group were divided into three subgroups:6 hour group,12 hour group and 24 hour group.The rats in the Sham group underwent the identical laparotomy but without Cecal ligation and puncture,and infused with normal saline 1 ml/h for 6 hours continuously.The NS group infused normal saline 1 ml/h for 6 hours continuously after Cecal ligation and puncture.The ES group infused esmolol 15mg/kg/h(1ml/h) for 6 hours continuously after Cecal ligation and puncture.Then the rats in each subgroup were killed at the corresponding time points to detect the levels of catecholamine, tumor necrosis factor-? and cardiac troponin T in the serum and the contents of toll-like receptor 4 in myocardium.And then the samples from the left ventricular apex were dealed with Hematoxylin-eosin and the changes of myocardial pathomorphology were observed through the optical microscope.Results1.Compared with Sham group,the levels of catecholamine of the ES group in serum at 6h and 12 h postoperatively were significantly increased(p<0.05),and the levels of catecholamine of the NS group in serum at 6h postoperatively weresignificantly increased(p<0.05);Compared with NS group,the levels of catecholamine of the ES group in serum at 6h and 24 h postoperatively were significantly increased(p<0.05).2.Compared with Sham group,the levels of tumor necrosis factor-? of the NS group and the ES group in serum at 6h,12 h and 24 h postoperatively were significantly increased(p<0.05);Compared with NS group,the levels of tumor necrosis factor-? of the ES group in serum at 6h,12 h and 24 h postoperatively were significantly decreased(p<0.05).3.Compared with Sham group,the levels of cardiac troponin T of the NS group and the ES group in serum at 6h,12 h and 24 h postoperatively were significantly increased(p<0.05);Compared with NS group,the levels of cardiac troponin T of the ES group in serum at 6h,12 h and 24 h postoperatively were significantly decreased(p<0.05).4.Compared with Sham group,the levels of toll-like receptor 4 of the NS group and the ES group in myocardium at 6h,12 h and 24 h postoperatively were significantly increased(p<0.05);Compared with NS group,the levels of toll-like receptor 4 of the ES group in myocardium at 6h,12 h and 24 h postoperatively were significantly decreased(p<0.05).5. Diffuse vacuolar degeneration, myocardial edema, myocardial fibers disarray, inflammatory cells infiltration and interstitial vascular congestion were seen at 6h after CLP in NS group;Myocardial edema, inflammatory cells infiltration and interstitial vascular congestion were alleviated at 12 h and 24 h after CLP in NS group,but myocardial necrosis occured and became more obvious at 24 h after CLP in NS group;The changes in ES group were alleviated than those in NS group and the pathology of the Sham group was normal.6.Compared with NS survival group,the seven-day survival rate of the ES survival group was not significantly increased(p>0.05).ConclusionEsmolol might have protective effects on myocardium in rats after CLP through improving the state of catecholamine secretion,supressing the release ofinflammatory cytokines,improving the inflammatory immune reactions and reducing the injury degree of myocardium.The mechanism may be relative to the inhibition of catecholamine cardiotoxicity via which esmolol improve the reactivity of beta-adrenergic receptors.