PROSTAGLANDINS AND THROMBOXANES IN LIVER FAILURE

我们最近的研究表明，扩张血管的前列腺素在 重症肝病患者维持肾血流灌注的关键作用 疾病。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。 目前的项目将调查强大的 血管紧张剂血栓素A2，作为潜在肾脏的原因 血管收缩，通常进展为严重的肾功能衰竭，称为 肝肾综合征。在这两种方法中都将使用多种方法技术 人体和动物研究以确保前列腺素和 血栓素测量。这些技术包括生物测定，几种 放射免疫分析、放射化学技术和气相色谱-质谱法 光谱分析。第一个项目将连续测量尿液 慢性肝功能衰竭患者前列腺素和血栓素水平的变化 肾脏损害的进展。对照组包括其他肾、肝 和血栓性疾病。初步数据显示血栓素增加 仅限于肝肾患者。第二个项目将调查 前列腺素和血栓素排泄与治疗的关系 肝功能衰竭患者的操作，如腹膜静脉分流，以 评估可能增加或减少肾血栓形成的因素 制作。第三个项目将确定肾和肾外 用我们的放射化学方法研究人类尿液中血栓素的来源 技巧。第四个项目继续我们的动物研究，以确定 引起肾脏高分泌的血流动力学要求 肝肾疾病模型中的血栓素。这些研究将 同时测定选择性血栓素抑制的效果。这个 长期目标是确定生理和病理功能 血栓烷作为肾循环的中介物。这些研究可能会导致 寻找一种选择性血栓素抑制的新的治疗方法 疾病如肝肾综合征。

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.