MICROVASCULAR CONTROL BY TISSUE FACTORS IN SEPSIS

脓毒症中组织因子对微血管的控制

基本信息

批准号：
3132792
负责人：
Richard N Garrison
金额：
$ 8.49万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-09-01 至 1989-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3132792
关键词：
Bacillus Escherichia coli acid base balance carbon dioxide tension decerebration disease /disorder model endotoxins laboratory rat microcirculation model design /development muscle metabolism oxygen consumption oxygen tension peritonitis postoperative state video recording system

项目摘要

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.

不受控制的败血症继续导致高发病率和死亡率手术病人。多个器官系统衰竭，即使是在遥远的地方部位，通常与脓毒症死亡有关，并且是氧气的利用在脓毒症患者身上得到了一致的证实。这该提案的主要前提是这两个观察结果是直接相关，器官衰竭的基础是缺氧利用率。这项研究将利用三种脓毒症大鼠模型。腹腔内通过注射 2 x 10-8 大肠杆菌接种物形成脓肿和 2 x 10-9 B. fragilis 进入大鼠失活的盲肠。在这个模型中，腹膜炎急性期随之而来，40% 的动物死亡 48 小时内，其余动物发展为慢性惰性腹腔内脓肿。该模型将在 24 小时和 4 点进行研究天。脓毒症的第二种模型将利用缓慢静脉输注在此期间进行了大肠杆菌内毒素的微血管观察输液。第三种模型涉及亚致死静脉输注活体大肠杆菌（6 x 10 8 生物体/100 克体重）。适当的年龄和体重匹配的非脓毒症动物将作为基线对照。直接体内观察提睾肌中不同大小的小动脉肌肉（一种高代谢组织）将通过电视显微镜制作。首先，对微血管直径的变化进行定量以进行比较高动力和血动力阶段的微血管现象三种动物模型中的败血症。纵向氧梯度（将测量小动脉树下血氧张力的降低在脓毒症的两个阶段中确定微血管水平败血症期间可能会发生氧气输送的改变。然后，组织环境氧分压 (pO2)、碳的局部变化的影响二氧化氮 (pCO2) 和氢离子 (pH) 对脓毒症动脉反应的影响被记录在三种动物模型中。系统性败血症和多系统器官衰竭经常被注意到外科服务。本研究将探讨改变的基本机制氧气利用和随后的器官衰竭，最终预测开发更有效的治疗方式的理由化粪池的人。