PROSTAGLANDINS AND THROMBOXANES IN LIVER FAILURE

我们最近的研究表明，血管扩张性肾上腺素发挥 在维持重度肝硬化患者的肾脏灌注中的关键作用 疾病 用抗炎药抑制前列腺素的产生 药物显著损害肾血流量和肾小球滤过率。 目前的项目将调查的作用， 血管收缩剂，血栓素A2，作为潜在肾损害的原因， 血管收缩，往往进展到严重的肾衰竭，所谓的 肝肾综合征 在这两个领域将使用多种方法技术。 人类和动物研究，以确保前列腺素的有效性， 血栓素测量。 这些技术包括生物测定， 放射免疫测定、放射化学技术和气相色谱-质谱 光谱法 第一个项目将连续测量尿液 肝衰竭患者在治疗过程中的前列腺素和血栓素 肾损害进展。 对照组包括其他肾脏、肝脏 和血栓性疾病。 初步数据显示血栓素 仅在肝肾患者中。 第二个项目将调查 前列腺素和血栓素排泄与治疗的关系 肝衰竭患者的操作，如腹膜静脉分流， 评估可能增强或减少肾血栓素的因素 生产 第三个项目将确定肾和肾外 来源的尿血栓素生产的人，使用我们的放射化学 技术. 第四个项目继续我们的动物研究， 引起肾分泌过多血液动力学要求 血栓烷在肝脏和肾脏疾病模型中的作用。 这些研究将 还确定选择性血栓素抑制的效果。 的 长期目标是确定生理和病理功能 血栓素作为肾循环的介质。 这些研究可能会导致 本发明涉及一种在这种疾病中具有选择性血栓烷抑制的新治疗方法， 肝肾综合征等疾病。

Our recent studies have demonstrated that vasodilatory prostaglandins play a key role in maintaining renal perfusion in patients with severe liver disease. Inhibition of prostaglandin production with anti-inflammatory drugs markedly impairs renal blood flow and glomerular filtration rate. The current project will investigate the role of the potent vasoconstrictor, thromboxane A2, as a cause of the underlying renal vasoconstriction that often progresses to severe renal failure, called the hepatorenal syndrome. Multiple methodology techniques will be used in both human and animal studies to assure the validity of prostaglandin and thromboxane measurements. The techniques include bioassay, several radioimmunoassays, radiochemical techniques, and gas chromatography-mass spectrometry. The first project will serially measure urinary prostaglandins and thromboxanes in patients with liver failure during the progression of renal impairment. Control groups include other renal, liver and thrombotic diseases. Preliminary data reveal increased thromboxane only in the hepatorenal patients. The second project will investigate the relationship of prostaglandin and thromboxane excretion to therapeutic maneuvers in liver failure patients, such as peritoneovenous shunt, to evaluate factors that may enhance or diminish renal thromboxanes production. The third project will determine the renal and extra-renal sources of urinary thromboxane production in man, using our radiochemical techniques. The fourth project continues our animal studies to determine the hemodynamic requirements that induce hypersecretion of renal thromboxanes in models of liver and kidney disease. These studies will also determine the effects of selective thromboxane inhibition. The long-term objective is to determine the physiologic and pathologic function of thromboxanes as mediators of renal circulation. These studies may lead to a new therapeutic approach with selective thromboxane inhibition in such disorders as hepatorenal syndrome.