Effects Of Shengmai Injection In Prevention And Treatment Of Early Postburn Shock Heart And Its Mechanism

Objective and backgroundSince 1980s,our serial studies have confirmed that myocardial damage occurrs during early stage following severe burns.The activation of RAS system in the heart itself may be the most important initiating factor in inducing myocardial ischemia and hypoxia.Because heart is the power organ of circulation,the early myocardial damage and cardiac reduction(before the significant reduction of blood volume due to the increased capillary permeability) may become one of the important trigering factors causing ischemic and hypoxic damage following severe burns.Based on this recognition,postburn heart shock iwas proposed in our previous reports.Therefore,it is of clinical importance to find out some new preventive and therapeutic measurements to alleviate postburn myocardial injury. In this study,preventive and therapeutic effects of Shengmai injection on shock heart and its mechanisms were investigated.Material and method1.Prospective clinical studyAccording to the enrolling and exclusive criteria,20 burn patients admitted to our burn institute from January to October,2005 were selected in this study.The patients were randomly divided into conventional treatment group and Shengmai injection treated group. Plasma cTnI,CK-MB and LDH were determined with routine methods.2.Animal experiments(1) Chamges of myocardial mechanics:54 healthy Wistar rats,weighing 210±20g, were randomly divided onti 3 groups:Normal control(group N,n=6);Burn control (group B,n=24),30%TBSAⅢburn was reproduced according to the method of our institute.The burn animals received fluid resucitation peritoneally with sodium lactate ringer's injection according to Parkland formula;and Shengmai injection treated group (group S,n=24),after subjected to 30%TBSAⅢburn and resucitated with sodium lactate ringer's injection.Animals were peritoneally given Shengmai injection of 4 ml·Kg^-1. LVSP,LVEDP,and +dp/dt max were determined(2) Study on mechanisms of Shengmai injection in alleviating myocardial damage72 healthy Wistar rats were treated and grouped as described above. Pathomorphological observations of myocardial tissues,myocardial MDA,myocardial caspase-3 activity and apoptosis of myocardial cells were investigated.Results1.Clinical prospective research1) Results of serum cTnIThe results showed that in both control and treatment groups,the serum content of cTnI reached its peak at 12 postburn hour(PBH).cTnI level of control group was 14.6 times higher than that of upper limit of normal level,cTnI value in the treatment group was 6.8 times more than that of our upper limit.Then it gradually decreased.But the cTnI level of treatment group was significantly lower than that of control group at 12,24 and 48 PBH(P＜0.05).2) Results of serum CK-MB and LDH activityAt 12 PBH,CK-MB and LDH in both groups reached their peak levels.Then they decreased gradually.Levels of CK-MB and LDH in the treatment group were significantly lower than those of control group at 12,24 and 24 PBH(P＜0.05).2.Changes of myocardial mechanical parameters in burn ratsIn control group,the changes in myocardial contractile and relaxation functions parameters,including LVSP,LVEDP and +dp/dt max,were all decreased within 12 PBH and raised at 24h post-burn,but were still lower than normal levels.In Shengmai injection treated group,all myocardial mechanical parameters were remarkably improved.The changes of myocardical pathomorphology were lessened,indicating that Shengmai injection improved the myocardial contractile and relaxation functions,and alleviated the myocardial injury in burn rats.3.Mechanisms of Shengmai injection in alleviating myocardial damageThere was no apoptotic cells in myocardial tissue of normal rats.There was less apoptotic cells detected in myocardial tissue in both groups at 3PBH,and more apoptotic cells at 6,12 and even 24PBH.However,the number of apoptotic cells in group S was less than that in group B at 6,12 and 24PBH(P＜0.01). Level of caspase-3 activity peaked at 3 and 6PBH in both groups.But caspase-3 activity in group S was significantly lower than that in group B at 6,12 and 24PBH (P＜0.05).The level of MDA of myocardial tissue raised markedly at 3PBH(p＜0.05),then peaked at 6 and 12PBH,and downtrended at 24PBH.The level of MDA of myocardial tissue in group S was significantly lower than that in group B at 12 and 24PBH(P＜0.01).Discussion and conclusion1.It was demonsrated that in our animal and clinical studies that severe myocardial damage,as reflected by increased cTnI,CK-MB,LDH and myocardial mechanical parameters,occurred in the early stage following burns.Shengmai injection may alleviate the early postburn myocardial damage.2.The mechanisms for the myocardial protection of Shengmai injection might be manifold.According to the finding of the present study,the main mechanism for Shengmai injection may be:(1) alleviating the activity of caspase-3 and reducing the number of apoptosis of myocardial cells.(2) alleviating lipid peroxidation,which decreases the level of MDA in myocardial tissue following servere burns.3.The clinical prospective investigation proved that resuscitation with administering of Shengmai injection was safe and effective.No side effects were found,thus supplying a new approach to prevent and treat early postburn myocardial damage.