INTESTINAL ISCHEMIA: PATHOPHYSIOLOGY AND DIAGNOSIS

急性肠缺血的高死亡率(50%-90%)很大程度上是由于 治疗前出现不可逆的组织损伤 干预。该项目建议调查以下方面 病理生理学、诊断和治疗适用于 缺血性胃肠道疾病患者的处理。少校 将努力研究血液动力学控制的基本机制。 内脏循环，特别是关于内脏循环的病理生理学 非阻塞性肠系膜缺血，胃粘膜应激性侵蚀， 缺血性肝功能衰竭，非结石性胆囊炎，缺血性胰腺炎， 和缺血性结肠炎在心源性、出血性和 感染性休克。在每种形式的休克的猪模型中，血液流向每一种 这些器官将被测量并对血流动力学参数进行量化。 使用特定的激动剂，以及解剖和药物阻断， 肾素-血管紧张素轴、交感神经系统的相关作用 和加压素将被评估为可能的深层次， 导致这些情况的选择性内脏血管痉挛。的作用 内脏阻容血管在内脏控制中的作用 全身血流动力学，特别是总外周阻力， (“后负荷”)和功能循环血容量(“前负荷”) 在这些州也有类似的评估。使用实际缺血的大鼠模型 模拟新生儿坏死性小肠结肠炎的组织损伤，胃 粘膜应激性侵蚀和节段性肠血管闭塞，这 项目还将直接调查上述项目的贡献 血管活性控制机制在这些疾病的发病机制中起重要作用。在……里面 这些相同的模型它还将使用特定的生成抑制剂 和氧自由基的活性来评估它们在 这些疾病中缺血后再灌注损伤的产生。最后， 本研究将探索早期识别肠道疾病的新方法 人类的缺血性疾病。血清内毒素、二胺氧化酶和 肌酸磷酸激酶的BB同工酶将被评估为 疑似肠源性疾病患者的早期肠缺血指标 血管妥协。此外，伽马相机图像和活动冲刷 ~(133)Xe~(133)Ne在腹膜腔内注射后的曲线 将评估其检测早期低流量状态的能力，之前 对缺血性组织损伤的发展起重要作用。这些研究将是 在怀疑患有肠系膜缺血或 绞窄性梗阻。

The high (50-90%) mortality of acute intestinal ischemia is due largely to the appearance of irreversible tissue damage prior to therapeutic intervention. This project proposes to investigate those aspects of pathophysiology, diagnosis and treatment that are applicable to the management of patients with ischemic gastrointestinal disease. The major effort will study the basic mechanisms of hemodynamic control of the splanchnic circulation, with specific reference to the pathophysiology of nonocclusive mesenteric ischemia, stress erosions of the gastric mucosa, ischemic liver failure, acalculous cholecystitis, ischemic pancreatitis, and ischemic colitis under conditions of cardiogenic, hemorrhagic, and septic shock. In pig models of each form of shock, blood flow to each of these organs will be measured and hemodynamic parameters quantitated. Using specific agonists, and anatomic and pharmacologic blockade, the relative roles of the renin angiotensin axis, sympathetic nervous system and vasopressin will be evaluated as possible mediators of the profound, selective splanchnic vasospasm that causes these conditions. The role of the splanchnic resistance and capacitance vessels in the control of systemic hemodynamics, specifically total peripheral resistance, ("afterload") and functional circulating blood volume ("preload") will be similarly evaluated in these states. Using rat models of actual ischemic tissue damage simulating neonatal necrotizing enterocolitis, gastric mucosal stress erosions, and segmental intestinal vascular occlusion, this project will also investigate directly the contributions of the above vasoactive control mechanisms to the pathogenesis of these conditions. In these same models it will also use specific inhibitors of the generation and activity of oxygen free radicals to evaluate their role in the production of post-ischemic reperfusion injury in these diseases. Finally, this study will investigate new means for early recognition of intestinal ischemic disease in man. Serum levels of endotoxin, diamine oxidase and the BB isoenzyme of creatinine phosphokinase will be evaluated as indicators of early bowel ischemia in patients suspected to have intestinal vascular compromise. In addition, gamma camera images and activity washout curves obtained following the intraperitoneal administration of 133Xenon will be evaluated for their ability to detect early low flow states, prior to the development of ischemic tissue damage. These studies will be conducted in patients suspected to have mesenteric ischemia or strangulation obstruction.