PATHOPHYSIOLOGIC, BIOCHEMICAL CHANGES OF THERMAL INJURY

由主要疾病引起的相关代谢/免疫学表现 热损伤引发导致主要器官功能障碍的状态 以及改变伤口愈合。 理解 各种激活的介体级联的相互关系是 方法利用标准化烧伤创面模型（小鼠、大鼠、兔 和豚鼠）、离体器官、细胞培养物和分子生物学方法。 准备解剖启动和延续的序列， 高动力-氧化应激状态特征主要热 外伤 每个器官系统的反应及其贡献是 评估。 活化的粘附白细胞在血液流动中的作用， 血管内凝血、内皮粘附和随后的细胞内 心脏、肠道和伤口中释放的有毒物质将 评估。 组织巨噬细胞反应产物及其相互作用 将检查肝脏中与实质细胞相关的 蛋白质合成和mRNA表达，以更好地定义或鉴定 可能影响其他主要器官（肺）的分泌产物。 的作用 内脏释放的介质与减少肠道屏障 功能将被定义并与其对其他器官的影响相关 应答 伤口的作用将通过检查伤口来确定 液体，用于与蛋白酶、粘附蛋白有关的成分变化 和生长因子的活性，它们与伤口愈合有关 顺序 动物模型的项目整合将允许评估 从完整的动物到细胞和分子水平。 MRI 光谱法将确定离子转移和酸的生物能量学 重要器官的基础平衡;离体心脏器官功能 制备物（Langendorf），分离的肌细胞和肝实质细胞 干扰;以及蛋白质合成与mRNA的亚细胞关系 调控 这些实验的结果预计将定义一个 各种特定的药理学方法， 预定烧伤后病理生理介质相互作用 的间隔 大量可用的临床材料保证了 完成这些评估。

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.