SPLANCHNIC HEMODYNAMICS IN PORTAL HYPERTENSION

门静脉高压的内脏血流动力学

• 批准号: 3471712
• 负责人: JAMES V SITZMANN
• 金额: $ 10.29万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3471712
• 关键词: glucagon; hemodynamics; hormone regulation /control mechanism; human subject; indicator dilution test; laboratory rabbit; liver circulation; liver cirrhosis; mesentery; particle; portal hypertension; prostacyclins; radiotracer; splanchnic nerves

Portal hypertension is one of the more serious clinical complications of advanced liver disease. Current therapy of portal hypertension is limited by our poor understanding of the basic mechanisms involved in its development and maintenance. Recent work has identified a 2-3 fold increase in portal venous inflow (forward flow theory) as an important factor in the maintenance of portal hypertension. Evidence now supports the idea that prostacyclin (PGI2) or glucagon (potent splanchnic vasodilators) may be involved in the increase flow phenomenon. This project proposes to determine whether the actions of PGI2 or glucagon are central to the development and maintenance of portal hypertension, if PGI2 or glucagon mediate or modulate the action of the autonomic nervous control of splanchnic hemodynamics, and finally, if the increase in portal hypertension of PGI2 and glucagon are related and quantitate their relative effects on portal blood flow. Part I will study whether PGI2 mediates or modulates the portal hemodynamic effects of the autonomic nervous system by utilizing selective blockade and stimulation of various limbs of the autonomic nervous system in the portal hypertensive and normal rabbit model. Part II will test the hypothesis that PGI2 may be related to the action of glucagon. Whether the elevations of PGI2 and glucagon are related via the autonomic nervous system will also be determined. Glucagon administration in rabbits with and without cyclo- oxygenase blockade as well as autonomic blockade/stimulation will be performed, and the effect on PGI2 production and splanchnic hemodynamics measured. Part III will attempt to determine the stimulus for the rise of PGI2, glucagon, and mesenteric flow observed in portal hypertensive animals by performing selective splanchnic vein ligation, portosystemic shunt, hepatic arterial ligation, and cirrhosis induced, and the effect on mesenteric, hepatic, and portal flow, pressure and resistance, and PGI2 and glucagon production, organ oxygen differences will be measured to determine the regulated variable causing portal hypertension. Part IV will attempt to confirm the role of PGI2/glucagon in portal hypertensive humans. Systemic and portal PGI2/glucagon and splanchnic blood flow will be measured. The effect of normalization of portal pressure (portosystemic shunt) on the hyperemia of human portal hypertension will be studied. The results of these studies will provide information about the pathophysiology of portal hypertension and indicate the hormonal/pharmacologic/anatomic manipulations which would favorably alter the sequelae of portal hypertension.

门静脉高压症是临床较严重的疾病之一 晚期肝病的并发症。 目前治疗 门静脉高压症由于我们对门静脉高压症了解甚少而受到限制。 其开发和维护所涉及的基本机制。 最近的工作发现门静脉增加了 2-3 倍 流入（正向流动理论）是影响流动的一个重要因素 维持门脉高压。 现在的证据支持 认为前列环素 (PGI2) 或胰高血糖素（强效内脏 血管扩张剂）可能与血流增加现象有关。 该项目建议确定 PGI2 或 胰高血糖素对于发育和维持至关重要 门静脉高压，如果 PGI2 或胰高血糖素介导或调节 内脏自主神经的调节作用 血流动力学，最后，如果门脉高压增加 PGI2 和胰高血糖素的相关性并定量它们的相对值 对门脉血流的影响。 第一部分将研究PGI2是否 介导或调节门脉血流动力学效应 通过利用选择性封锁和自主神经系统 刺激各肢体的自主神经系统 门脉高压和正常兔模型。 第二部分将测试 PGI2 可能与以下作用有关的假设 胰高血糖素。 PGI2和胰高血糖素的升高是否 通过自主神经系统相关的也将被确定。 在有或没有环化的兔子中给予胰高血糖素 氧酶阻断以及自主神经阻断/刺激 将进行，以及对 PGI2 产生和的影响 测量内脏血流动力学。 第三部分将尝试 确定 PGI2、胰高血糖素和 门脉高压动物中观察到的肠系膜流量 进行选择性内脏静脉结扎、门体静脉结扎 分流术、肝动脉结扎术和诱导的肝硬化，以及 对肠系膜、肝和门脉血流、压力和 抵抗力、PGI2 和胰高血糖素生成、器官供氧 将测量差异以确定调节变量 引起门脉高压。 第四部分将尝试确认 PGI2/胰高血糖素在门脉高压症患者中的作用。 系统性 门静脉 PGI2/胰高血糖素和内脏血流量将 测量。 门静脉压力正常化的影响 （门体分流术）对人体门脉充血的影响 将研究高血压。 这些研究的结果将 提供有关门脉病理生理学的信息 高血压并指出激素/药理学/解剖学 将有利地改变门户后遗症的操作 高血压。