MICROVASCULAR CONTROL BY TISSUE FACTORS IN SEPSIS

不受控制的脓毒症继续造成高发病率和死亡率 那个外科病人。多个器官系统出现故障，即使是在远程 部位，通常与脓毒症死亡有关，并且是 在败血症患者中，氧气的利用一直被证明。这个 这一提议的主要前提是这两个观察结果是 器官衰竭的基础是缺氧性 利用率。 这项研究将利用三种脓毒症大鼠模型。腹内一次 接种2×10-8的大肠杆菌会形成脓肿。 和2×10~(-9)杆菌进入灭活大鼠盲肠。在这 模型出现腹膜炎急性期，40%的动物死亡 在48小时内，其余的动物发展成慢性惰性 腹内脓肿。这一模式将在24小时和4点进行研究 几天。第二种脓毒症模型将使用缓慢的静脉输注 大肠埃希氏菌内毒素及其微血管观察 输液。第三种模式是亚致死性静脉输注活体 大肠杆菌(6×108个生物体/100克体重)。适当的年龄和 体重匹配的非败血症动物将作为基线对照。 提睾肌内不同大小小动脉的直接活体观察 肌肉(一种高度新陈代谢的组织)将由电视显微镜制作。 最初，将对微血管直径的变化进行量化以进行比较 高动力和高动力时相中的微血管现象 三种动物模型均出现脓毒症。纵向氧梯度(The 血氧分压降低)将被测量到动脉树下 以确定脓毒症的两个阶段的微血管水平 脓毒症期间可能会发生氧输送的改变。那么， 局部改变对组织-环境氧分压(PO2)、碳水化合物的影响 二氧化碳(PCO2)和氢离子(PH)对脓毒症小动脉反应的影响 被记录在三个动物模型中。 全身性脓毒症和多系统器官衰竭在 外科服务。这项研究将解决改变的基本机制 氧气利用和随后的器官衰竭，最终预测 年开发更有效的治疗方式的理由 败血症患者。

Uncontrolled sepsis continues to generate a high morbidity and mortality in the surgical patient. Failure of several organ systems, even at remote sites, is often associated with death from sepsis, and a major defect in oxygen utilization has been consistently demonstrated in septic man. The primary premise of this proposal is that these two observations are directly related and that the basis for organ failure is a defect in oxygen utilization. This research will utilize three rat models of sepsis. An intra-abdominal abscess will be formed by the injection of an inoculum of 2 x 10-8 E. coli and 2 x 10-9 B. fragilis into the devitalized cecum of rats. In this model, an acute phase of peritonitis ensues with 40% of the animals dying within 48 hours, and with the remaining animals developing chronic indolent intra-abdominal abscesses. This model will be studied at 24 hours and at 4 days. A second model of sepsis will utilize slow intravenous infusion of E. coli endotoxin with mocrovascular observation being made during this infusion. The third model inolves sublethal intravenous infusion of live E. coli (6 x 10 8 organisms/100 gm body weight). Appropriate age and weight-matched nonseptic animals will serve as baseline controls. Direct in vivo observations of different sized arterioles in the cremaster muscle (a high metabolism tissue) will be made by television microscopy. Initially, changes in microvascular diameter will be quantitated to compare microvascular phenomena during the hyperdynamic and hpodynamic phases of sepsis in the three animal models. The longitudinal oxygen gradient (the decrease in blood oxygen tension) down the arteriolar tree will be measured in both phases of sepsis to determine the microvascular level where alterations in oxygen delivery might occur during sepsis. Then, the effects of local changes in tissue-environment oxygen tension (pO2), carbon dioxide (pCO2) and hydrogen ion (pH) on arteriolar responses to sepsis will be documented in the three animal models. Systemic sepsis and multiple systems organ-failure are frequently noted on surgical services. This study will address the basic mechanisms of altered oxygen utilization and subsequent organ failure, eventually to predict rationale for the development of more effective treatment modalities in septic man.