INTESTINAL ISCHEMIA: PATHOPHYSIOLOGY AND DIAGNOSIS

急性肠缺血的高死亡率（50- 90%）是由于 在很大程度上是因为在手术前出现了不可逆的组织损伤， 治疗干预 该项目旨在调查这些 病理生理学、诊断和治疗方面， 提供适用于患者管理的信息， 所有形式的肠缺血性疾病。 第一部分将研究基本 非闭塞性肠系膜缺血（NOMI）的机制，使用选择性 对肾素-血管紧张素轴和交感神经系统的旁粘膜阻滞 在由心包填塞产生的NOMI猪模型中的神经系统中。 我们还将评估血管痉挛在改变侧支循环中的作用， 从而影响在闭塞性肠系膜缺血期间的组织损伤， 大鼠 第二部分将研究低流量产生的机制， 肠组织损伤 我们将评估可能的保护作用， 果糖1，6二磷酸作为肠道厌氧能量来源 大鼠缺血。 在同一模型中，我们将研究 特异性药物对再灌注超氧自由基损伤作用 封锁 最后，我们将评估纤溶治疗的使用， 尿激酶溶解微血管血栓，增强缺血后 微血管通畅和再灌注，从而改善组织恢复 在经受节段性肠系膜血管闭塞的兔中。 第三部分 将研究早期识别肠缺血的新方法， 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 节段性血管狭窄兔早期肠缺血的指标 在疑似肠血管闭塞的患者中， 妥协 此外，伽马相机图像和活动洗脱曲线 将在腹膜内施用133氙后获得 评估其检测早期低流量状态的能力， 组织损伤的发展，并定量“有效腹膜 灌注”作为肠系膜血流的指标。 这些研究报告将 在大鼠和疑似肠缺血的患者中进行， 肠系膜闭塞、NOMI或绞窄性梗阻。 我们所有的结果 应直接适用于此类患者。

The high (50-90 percent) 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 likely to provide information that is applicable to the management of patients with all forms of ischemic disease of the bowel. Part I will study the basic mechanism of nonocclusive mesenteric ischemia (NOMI) using selective paramacologic blockade of the renin-angiotensin axis and the sympathetic nervous system in a pig model of NOMI produced by pericardial tamponade. We will also evaluate the role of vasospasm in altering collateral flow and thus influencing tissue injury during occlusive mesenteric ischemia in the rat. Part II will investigate mechanisms by which low flow produces intestinal tissue injury. We will evaluate the possible protective role of fructose 1, 6 diphosphate as an anaerobic energy source during bowel ischemia in the rat. In the same model we will study the role of superoxide free radical injury during reperfusion by specific pharmacologic blockade. Finally, we will evaluate the use of fibrinolytic therapy with urokinase to lyse microvascular thrombi, enhance post-ischemic microvascular patency and reperfusion, and thereby improve tissue recovery in rabbits subjected to segmental mesenteric vascular occlusion. Part III will investigate new means for early recognition of intestinal ischemic disease in animals and man. Serum levels of endotoxin, diamine oxidase and the BB isoenzyme of creatinine phosphokinase will be evaluated as indicators of early bowel ischemia in rabbits with segmental vasular occlusion and in patients suspected to have intestinal vascular compromise. In addition, Gamma camera images and activity washout curves obtained following the intraperitoneal administration of 133 Xenon will be evaluated for their ability to detect early low flow states, prior to the development of tissue damage, and to quantitate "effective peritoneal perfusion" as an index of mesenteric blood flow. These studies will be conducted in rats and in patients with suspected ischemic bowel from mesenteric occlusion, NOMI or strangulation obstruction. All our results should be directly applicable to such patients.