Protective Effects Of Enalaprilat Injection On Myocardial Damage During Early Stage Following Burn Injury

Objective and backgroundOur 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.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.Therefore, prevention of postburn myocardial damage may be of importance in the treatment of severe burns.In this study,the preventive and therapeutic effects of Enalaprilat injection(ENA) on postburn shock heart and its mechanisms were investigated.Material and method1.Dose-effect Relationship of Enalaprilat Injection on organ damage during early stage following burn injury in rats54 SD rats were subjected to 30%total body surface areaⅢscald injury.The scalded rats were randomly divided into scald group(B group,with conventional fluid transfusion after scald) and ENA treated group,and the later was divided into 3 groups (E1 group,with intraperitoneal injection of 1mg/kg ENA after scald;E2 group,with intraperitoneal injection of 2mg/kg ENA after scald;and E3 group,with intraperitoneal injection of 4mg/kg ENA after scald).Another 6 rats were used as normal control.AOSP, AODP,MAP,AngⅡ,Bun,Cr,CK,ALT,AST were investigated at 6 and 12h post burn.The histologic changes in heart,liver,lung,kidney,and intestine were examined at 6 and 12h post burn.2.Protective effects of Enalaprilat Injection on myocardial damage during early stage following burn injury in rats84 SD rats were subjected to scald injury,and the rats were randomly divided into scald group and ENA treated group as described above.Another 6 rats were used as normal control.Plasma cTnI and CK-MB concentrations were measured by enzyme linked immunosorbent assay,histologic changes in myocardium were observed at 1,3,6,12 and 24h post burn.The levels of AngⅡin myocardial tissues of were investigated at 1,3,6,12 and 24h post burn.But the plasma cTnI and CK-MB concentrations and the level of AngⅡin myocardial tissues of the E2 and E3 groups were investigated at 6 and 12h post burn.3.Protective effects of Enalaprilat Injection on the myocardial mechanic damages during early stage following burn injury in rats84 SD rats were subjected to scald injury,and the rats were randomly divided into scald group and ENA treated group as described above.Another 6 rats were used as normal control.The myocardial mechanic parameters were investigated at 1,3,6,12 and 24h in scald group and E1 group,and at 6 and 12h in E2 and E3 groups post burn.Results1.Dose-effect Relationship of Enalaprilat Injection on organ damage during early stage following burn injury in ratsLevels of AngⅡ,Bun,Cr,CK,ALT,AST in the 3 ENA treated groups were significantly lower than those in scald group at 6 and 12 hours following scald.But the levels in the E1 group was the lowest among the 3 ENA groups.Levels of AOSP,AODP, MAP in the 3 ENA treated groups were significantly higher than those in the scald group, but the levels in E1 group was the highest at 6 and 12 hours following scald.Parameters reflecting heart,liver,lung,kidney were all increased after scald.The histologic changes of these organs were alleviated by use of enalaprilat Injection.2.Protective effects of Enalaprilat Injection on myocardial damage during early stage following burn injury in ratsSerum cTnI and CK-MB levels at 1,3,6,12,24 h after scald were significantly higher than normal(P＜0.01),and those in the 3 ENA groups were lower than those in group B(P＜0.01-0.05).The level of AngⅡin myocardial tissues in the 3 ENA treated groups were all lower than those in group B at 6 and 12h post scald.At 3h after scald,fiber engorgement,transverse striation derangement,cell boundary unsharpness,cytoplasm destruction,intercellular substance edema were observed in myocardial tissues.The pathomorphological changes were aggravated at 6 and 12 h after scald,and dissolvation,degeneration and necrosis ocurred,which were mild in the treated groups than that in group B.3.Protective effects of Enalaprilat Injection on the myocardial mechanic damages during early stage following burn injury in ratsLevels of LVSP,LVEDP,and LV±dp/dtmax were markedly decreased from 3 h follwing scald and remained at a level significantly lower than the normal control.The myocardial mechanic parameters in ENA treated groups were obviously improved,and were significantly higher than those in scald group at 6 and 12 hours following scald.The myocardial mechanic parameters in E1 group was the highest among the 3 treated groups at 6 and 12 post-scald hours.Discussion and conclusion1.The use of Enalaprilat injection in small dose(1mg/kg) can obviously decrease the level of AngⅡin blood,and protect the organs from damage following scald,with no obvious side-effect on blood pressure.The dose of(2mg/kg and 4mg/kg)Enalaprilat injection can lower the AngⅡlevel in blood,and blood pressure,which may aggravate organ damage.2.The use of Enalaprilat injection in small dose(1 mg/kg) can alleviate myocardial damage and improve the heart function in many ways,such as reducing the level of angiotensinⅡin myocardial tissues and blood,clearing oxygen free radicals,improving the myocardial cell energy metabolism etc.Therefore,it has more protective effects in prevention of myocardial damage following scald.3.The use of Enalaprilat injection in small dose(1mg/kg) can significantly improve the myocardial mechanic parameters in burned rats,and maintain the hemodynamics in a stable status,which is helpful for shock treatment following severe burn.4.In summary,the effect of Enalaprilat injection is stable.The use of 1 mg/kg Enalaprilat injection can significantly improve the myocardial mechanic parameters,with no obvious side-effect on blood pressure,suggesting that Enalaprilat(lower than 1 mg/kg) may be beneficial for the prevention and treatment of myocardial damage following severe burn.