PATHOPHYSIOLOGIC, BIOCHEMICAL CHANGES OF THERMAL INJURY

重症肺炎引起的相关代谢/免疫学表现 热损伤引发主要器官功能障碍的状态 除了改变，还会痊愈。对这一概念的理解 各种激活的介体级联的相互关系是 利用标准化烧伤创面模型(小鼠、大鼠、兔)进行探讨 和豚鼠)，分离的器官，细胞培养和分子 准备解剖启动和永久化 高热应激高动力-氧化应激状态特征 精神创伤。每个器官系统及其贡献的反应是 已评估。活化的粘附性白细胞在血流和血液动力学中的作用 血管内凝血、内皮细胞黏附和随后的细胞内 在心脏、肠道和伤口中释放的有毒物质将 已评估。组织巨噬细胞反应产物及其相互作用 肝脏中的实质细胞将被检查与 蛋白质合成和mRNA表达以更好地定义或识别 可能影响其他主要器官(肺)的分泌性产品。角色 内脏释放的介质与肠道屏障的降低有关 功能将被定义，并与它们对其他器官的影响相关 回应。伤口的作用将通过检查伤口来确定 液体，用于与蛋白酶、粘附性蛋白相关的成分变化 和与伤口愈合有关的生长因子活性。 序列。 动物模型的项目集成将允许对 从完整的动物到细胞和分子水平的光谱。磁共振成像 光谱分析将确定离子转移和酸的生物能量学 重要器官的基础平衡；离体心的器官功能 制剂(朗恩多夫)、分离的心肌细胞和实质肝细胞 蛋白质合成与信使核糖核酸的亚细胞关系 监管。这些实验的结果预计将定义一个 各种特定的药理学方法中断 烧伤后预先确定的病理生理介质相互作用 间隔时间。可获得的大量临床材料确保了 完成这些评价。

The interrelated metabolic/immunologic manifestations caused by major thermal injury initiate a state resulting in malfunction in major organs as well as altering would healing. Understanding of the interrelationships of the various activated mediator cascades is approached utilizing standardized burn wound models (mice, rats, rabbits and guinea pigs), isolated organs, cell cultures and molecular preparations to dissect the sequence that initiates and perpetuates the hyperdynamic - oxidative stress state characteristic of major thermal trauma. The response of each organ system and its contributions is to be evaluated. The role of activated adherent leukocytes in blood flow and intravascular clotting, endothelial adhesion and subsequent intracellular toxic products released in the heart, intestine and wounds will be evaluated. Products of the tissue macrophage response and its interaction with parenchymal cells in the liver will be examined in relation to protein synthesis and mRNA expression to better define or identify secretory products that may affect other major organs (lungs). The role of splanchnic released mediators associated with decrease gut barrier function will be defined and related to their effect on other organ responses. The role of the wound will be defined by examining wound fluids, for compositional changes related proteinase, adhesive proteins and growth factor activity which are related to the wound healing sequence. The project integration of the animal models will permit evaluation of the spectrum from intact animal to the cell and molecular level. MRI spectrometry will determine the bioenergetics of ion transfer and acid base balance of vital organs; organ function in isolated heart preparations (Langendorf), isolated myocyte and parenchymal liver cell perturbations; and subcellular relations of protein synthesis to mRNA regulation. The results of these experiments are expected to define a variety of specific pharmacologic approaches that interrupt pathophysiologic mediator interactions at pre determined pos-burn intervals. The large volume of clinical material available assures the completion of these evaluations.