SPLANCHNIC VASODILATORS IN PORTAL HYPERTENSION

门静脉高压症是临床上较为严重的疾病之一。 晚期肝病的并发症。当前的治疗方法 门静脉高压症受限于我们对门静脉高压症 它的开发和维护所涉及的基本机制。 最近的研究发现，门静脉的数量增加了2-3倍。 作为一个重要因素的流入(正向流动理论) 门静脉高压症的维持。现在有证据支持 前列环素(PGI2)或胰高血糖素(内脏强效) 血管扩张剂)可能参与了血流增加现象。 该项目建议确定PGI2或 胰高血糖素对血管的发育和维持至关重要 门静脉高压症，如果PGI2或胰高血糖素介导或调节 内脏自主神经控制的作用 血流动力学，最后，如果门静脉高压症的增加 前列环素与胰升糖素的相关性及定量研究 对门脉血流的影响。第一部分将研究PGI2是否起作用 作为一种局部或全身激素，检查PGI2 介导或调节门脉血流动力学效应 自主神经系统利用选择性阻断和 刺激自主神经系统的不同肢体 门静脉高压症及正常兔模型。第二部分将测试 前列环素2可能与血管紧张素转换酶的作用有关的假设 高血糖素。前列环素和胰高血糖素的升高是否 与自主神经系统相关的也将被确定。 兔胰高血糖素给药前后的比较 氧合酶阻断和自主神经阻断/刺激 以及对PGI2生产和生产的影响 测量内脏血流动力学。第三部分将尝试 确定前列腺素I2、胰升糖素和胰岛素升高的刺激因素 门脉高压动物肠系膜血流的动态观察 进行各种解剖操作。选择性内脏 静脉结扎、门体分流术、肝动脉结扎术 以及对肠系膜的影响， 肝脏、门静脉血流、压力和阻力，以及PGI2和 胰高血糖素的产生，器官氧的差异将被测量 确定引起门静脉高压症的调节变量。 这些研究的结果将提供有关 门静脉高压症的病理生理和提示 荷尔蒙/药物/解剖操作 有利于改变门静脉高压症的后遗症。

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 the 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 acts as a local or systemic hormone and examine 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 various anatomic manipulations. Selective splanchnic vein ligation, portosystemic shunt, hepatic arterial ligation will be performed, 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. 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.