SPLANCHNIC HEMODYNAMICS IN PORTAL HYPERTENSION

门静脉高压症是临床上较严重的疾病之一， 晚期肝病的并发症。 目前的治疗 门静脉高压症是有限的，我们的了解不足， 参与其发展和维持的基本机制。 最近的工作已经确定了门静脉癌栓的2-3倍增加， 流入（前向流理论）作为一个重要因素， 维持门静脉高压。 现在有证据表明， 前列环素（PGI 2）或胰高血糖素（强效内脏刺激剂） 血管扩张剂）可能参与流量增加现象。 该项目建议确定PGI 2或 胰高血糖素是发展和维持 门静脉高压症，如果PGI 2或胰高血糖素介导或调节 内脏自主神经控制作用 血液动力学，最后，如果门静脉高压症的增加 的PGI 2和胰高血糖素相关，并定量其相对 对门静脉血流量的影响。 第一部分将研究PGI 2 介导或调节门静脉血流动力学效应， 自主神经系统，利用选择性阻滞， 刺激自主神经系统的各个分支， 门静脉高压症和正常家兔模型。 第二部分将测试 PGI 2可能与以下作用有关的假设： 胰高血糖素 PGI 2和胰高血糖素的升高是否 也将确定通过自主神经系统相关的。 在有和没有环- 氧合酶阻断以及自主神经阻断/刺激 将进行，并对PGI 2生产和 测量内脏血流动力学。 第三部分试图 确定PGI 2、胰高血糖素升高的刺激， 门静脉高压症动物肠系膜血流观察 进行选择性内脏静脉结扎，门体静脉 分流、肝动脉结扎和肝硬化， 对肠系膜、肝脏和门静脉血流、压力和 阻力，PGI 2和胰高血糖素的产生，器官氧 将测量差异以确定调节变量 导致门静脉高压。 第四部分将试图确认 PGI 2/胰高血糖素在门静脉高压症患者中的作用。 系统性 门脉PGI 2/胰高血糖素和内脏血流量将 测定了 门静脉压力正常化的作用 （门体分流）对人门静脉充血的影响 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 操作，这将有利于改变后遗症的门户网站 高血压

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.