INTESTINAL ISCHEMIA: PATHOPHYSIOLOGY AND DIAGNOSIS

急性肠缺血的高死亡率（50-90%）主要是由于 治疗前出现不可逆的组织损伤 干预 本项目旨在研究以下方面： 病理生理学，诊断和治疗，适用于 缺血性胃肠道疾病患者的管理。 主要 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 非闭塞性肠系膜缺血，胃粘膜的应激性糜烂， 缺血性肝功能衰竭，非结石性胆囊炎，缺血性胰腺炎， 和缺血性结肠炎的条件下，心，出血， 败血性休克 在每种形式的休克的猪模型中，血液流向每一个 将测量这些器官并定量血液动力学参数。 使用特定的激动剂，以及解剖学和药理学阻断， 肾素血管紧张素轴、交感神经系统的相对作用 和加压素将被评估为可能的介质的深刻， 选择性内脏血管痉挛导致这些情况。 的作用 内脏血管的电阻和电容 全身血流动力学，特别是总外周阻力， 将测量功能性循环血量（“后负荷”）和功能性循环血量（“前负荷”）。 在这些国家也有类似的评价。 使用大鼠缺血模型， 组织损伤模拟新生儿坏死性小肠结肠炎，胃 粘膜应激性糜烂和节段性肠血管闭塞， 项目还将直接调查上述贡献 血管活性控制机制的发病机制，这些条件。 在 这些相同的模型，它也将使用特定的抑制剂的生成 和氧自由基的活性，以评估它们在 在这些疾病中产生缺血后再灌注损伤。 最后， 这项研究将探索新的手段，为早期识别肠 人缺血性疾病血清内毒素、二胺氧化酶和 肌酸酐磷酸激酶的BB同工酶将被评价为 疑似肠缺血患者的早期肠缺血指标 血管受损 此外，伽马相机图像和活动冲洗 133氙腹腔注射后获得的曲线 将评估其检测早期低流量状态的能力， 缺血性组织损伤的发展。 这些研究报告将 在疑似肠系膜缺血的患者中进行，或 窒息性梗阻

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.