Renin-angiotension System Imbalance Mediates Myocardial Damage At Early Stage Following Severe Burns In Rats

Myocardial damage may occur due to severe burn at early stage. Because of the special importance of the heart, its damage may not only cause cardiac dysfunction, but also induce or exacerbate burn shock. Ischemia/hypoxia is the important factor for myocardial damage during early postburn stage.Local rennin angiotensin system(RAS) existing in heart can synthesize and release rennin angiotensin. Different from circulatory RAS, the local RAS only effects on the heart itself to regulate myocardial regional blood flow, vascular tone and myocardial contractility. However, little is known about the contribution of RAS in myocardial damage during early postburn stage.The purpose of present study is to observe the changes of RAS components and its effects on heart function and myocardial damage, and to reveal the mechanism of heart damage and endogenous protection at early stage postburn by regulating RAS.Material and MethodsBoth in vivo and in vitro experiments were carried out in the study.1. In in vivo study, rats inflicting with 30% TBSA of full-thickness burns were used. The changes of RAS bioactive components in 24h postburn, and hemodynamics, myocardial mechanical indices, serum CTn-I level were investigated.2. Effects on heart function and myocardial damage by using Enalaprilat and Ang(1-7) to regulate the ACE-AngII axis and the ACE2-Ang(1-7) axis were investigated. Hemodynamics, myocardial mechanical indices, serum CTn-I level were assayed.3. An isolated heart Langendorff perfusion system was established. The isolated heart was inflicted with burn sera. Myocardial mechanical indices, coronary flow(CF) and LDH,CK level in coronary flow fluid were detected.4. Primary SD rat cardiac microvascular endothelial cells (CMEC) were cultured , stimulated with burn sera. CMEC vitality, NO, LDH and SOD level in culture fluid were assessed. Results:1. Myocardial damage occurred soon after severe burn, hemodynamics, myocardial mechanical indices (reflected by LVSP,LVEDP and±dp/dtmax) decreased to the lowest at 6h. Serum CTn-I peaked at 6h. ACE–AngII axis in myocardial and serum reased rapidly at 1h, peaked at 6h postburn. However, myocardial ACE2 was not activated obviously .2. After using Enalaprilat and Ang(1-7), the hemodynamics, myocardial mechanical indics including LVSP, LVEDP and±dp/dtmax were improved and serum CTn-I decreased obviously.3. The results of the isolated heart Langendorff perfusion system showed that CF and left cardiac function decreased obviously, and LDH, CK level in coronary flow fluid increased obviously, indicating that decrease of left ventricle function and myocardial damage may cause the decreasing CF after RAS activation. CF increased, and CK, LDH decreased after Enalaprilat and Ang(1-7) treatment.4. Primary CMEC from SD rat was uccessfully cultured. After stimulated by burn sera for 12h, the vitality of CMEC and levels of SOD, NO in culture fluid were decreased, and LDH increased. Cell vitality and level of SOD, NO in culture fluid increased, and LDH decreased by using burn sera containing Enalaprilat and Ang(1-7).Conclusion:1. Heart dysfunction and myocardial damage occurred immediately following severe burns, which further proved the"shock heart"theory of ischemic/hypoxic injury.2. As the important regulating system of circulation, ACE-AngII axis of RAS was rapidly activated at early stage postburn, which showed time-effect relationship with myocardial damage. But ACE2 was not activated, causing imbalance of ACE2-Ang(1-7) axis and ACE-AngII axis. It was indicated the imbalance of RAS may be one of the important reasons for heart damage. Actively regulating ACE2-Ang(1-7) axis and ACE-AngII axis at early stage postburn may be the important target to lessen myocardial ischemic injury.3. Myocardial damage was lessened by initiatively regulating the imbalance of ACE2-Ang(1-7) axis and ACE-AngII axis at early stage of severe burn, which indicated the imbalance of RAS was one of the important reasons for heart damage at early stage postburn. 4. By regulating RAS, CF was increased, left ventricle function was improved and myocardial damage was lessened,which imported that decrease of CF caused by RAS activation was the important reason for heart damage.5. Following burn sera stimulation, vitality of CMEC and level of SOD,NO in culture fluid was decreased, LDH increased. CMEC function was improved after treating with burn sera containing Enalaprilat and Ang(1-7). It is concluded that RAS activation led to heart damage at early stage postburn not only by affecting heart perfusion but also function of endothelial cell.