MICROVASCULAR CONTROL BY TISSUE FACTORS IN SEPSIS

脓毒症中组织因子对微血管的控制

• 批准号: 3132791
• 负责人: Richard N Garrison
• 金额: $ 8.62万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 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/3132791
• 关键词: Bacillus; Escherichia coli; acid base balance; carbon dioxide tension; decerebration; disease /disorder model; endotoxins; microcirculation; model design /development; muscle metabolism; oxygen consumption; oxygen tension; peritonitis; postoperative state

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产生高发病率和死亡率 手术患者。 几个器官系统的故障，即使在遥控处 地点通常与败血症死亡有关，并且是主要缺陷 在化粪池中，氧气的利用一直始终得到证明。 这 该提议的主要前提是，这两个观察结果是 直接相关，器官失效的基础是氧缺陷 利用率。 这项研究将利用三种大鼠败血症模型。 腹腔内 脓肿将通过注射2 x 10-8大肠杆菌形成 和2 x 10-9 B. Fragilis进入大鼠的失去活力。 在这个 模型是腹膜炎的急性阶段，有40％的动物死亡 在48小时内，其余动物发展为慢性懒惰 腹内脓肿。 该模型将在24小时和4小时进行研究 天。 第二种败血症模型将利用缓慢的静脉输注 在此期间进行了大肠杆菌内毒素，并具有多血血管观察 输液。 第三个模型iNOLVES静脉注射活的现场注入 大肠杆菌（6 x 10 8生物/100克体重）。 适当的年龄和 体重匹配的非污点动物将用作基线控制。 直接在Cremaster中对不同大小的动脉的体内观测 肌肉（高代谢组织）将通过电视显微镜进行。 最初，将定量微血管直径的变化以比较 在高血管和HP型学阶段的微血管现象 三种动物模型中的败血症。 纵向氧梯度（ 将测量小动脉树的血氧张力减少） 在败血症的两个阶段中，以确定微血管水平 败血症期间可能发生氧气递送的改变。 然后， 组织 - 环境氧张力（PO2），碳局部变化的影响 在小动脉对败血症的反应上的二氧化物（PCO2）和氢离子（pH）将会 在三种动物模型中记录。 经常在 外科服务。 这项研究将解决改变的基本机制 氧利用和随后的器官故障，最终预测 开发更有效治疗方式的理由 化粪池男人。