VASCULAR RESPONSE TO HEMORRHAGE IN PORTAL HYPERTENSION

失血性休克是门脉最常见、最致命的并发症。 高血压(PHT)。门静脉高压症患者对大出血的耐受性很差， 有发生肾功能衰竭的高风险，以及成人呼吸道疾病 窘迫综合症。目前的治疗方式实际上可能会加剧 出血的根本原因。我们发展理性的能力 门静脉高压症休克的治疗取决于更彻底的 了解门静脉血管反应。 最近的研究表明，在门静脉高压症中，门静脉血管系统成为 部分原因是前列环素(PGI2)过多， 肠系膜血管产生的血管扩张剂；反应减弱 内源性血管收缩药(血管紧张素II、精氨酸加压素)。 在出血和容量复苏后，实际上门脉压力 上升至高于基线，重新创造了持续的风险因素 在流血。我们的实验室最近显示了这种异常的血流动力学 门静脉高压症对出血/复苏的反应可能是通过一种 内脏静脉和肠系膜动脉的异常反应 血管系统对血管紧张素II、血管加压素和前列环素的作用。 这项建议试图确定假定的荷尔蒙之间的关系 内脏血流的介质：前列腺素I2、血管紧张素II和精氨酸 血管加压素在失血性休克血管反应异常中的作用 在PHT。采用门静脉部分结扎模型和门静脉高压症模型 兔胆管结扎后肝硬变模型的建立 在正常和PHT动物中，无论是否有复苏，都会产生复苏 特定的阻滞剂/激动剂。前列腺素和多肽水平/作用将是 测量以及全身、内脏和门静脉的侧支 血流动力学。在同一模型中，PGI2、血管紧张素II和血管紧张素转运蛋白 将对受体进行检测。研究以确定潜在的机制 内脏血管对出血的反应，以及对 荷尔蒙的作用就会完成。 这些实验应该提供对我们理解至关重要的信息 门静脉高压症和失血性休克；并直接导致 开发临床有效的治疗方案。

Hemorrhagic shock is the commonest and most lethal complication of portal hypertension (PHT). Patients with PHT tolerate massive hemorrhage poorly, with a high risk of developing renal failure, and adult respiratory distress syndrome. Current treatment modalities may actually aggravate the underlying causes of the bleeding. Our ability to develop rational treatment for shock in portal hypertension depends upon a more thorough understanding of the portal vascular response. Recent work has indicated that in PHT, the portal vasculature becomes "hyperdynamic", due in part to excess amounts of prostacyclin (PGI2), a vasodilator produced by the mesenteric vessels; and a diminished response to endogenous vasoconstrictors (angiotensin II, arginine vasopressin). Following hemorrhage and volume resuscitation, portal pressure actually rises to higher than baseline, recreating the risk factors for continued bleeding. Our laboratory has recently shown this abnormal hemodynamic response to hemorrhage/resuscitation in PHT may possibly be mediated by an abnormal response of the splanchnic venous and mesenteric arterial vasculature to angiotensin II, AVP, and PGI2. This proposal seeks to determine the relationship of the putative hormonal mediators of splanchnic blood flow: PGI2, angiotensin II, and arginine vasopressin (AVP) in the abnormal vascular response to hemorrhagic shock in PHT. Using both the partial portal vein ligation model of PHT and the bile duct ligated model of cirrhosis in the rabbit, hemorrhage and resuscitation will be produced in normal and PHT animals with and without specific blockade/agonists. Prostanoid and peptide levels/action will be measured as well as systemic, splanchnic, and portocollateral hemodynamics. In the same model, PGI2, angiotensin II, and AVP vascular receptors will be assayed. Studies to determine the mechanisms underlying the splanchnic vascular response to hemorrhage, and the response to hormonal action will be done. These experiments should provide information central to our understanding of portal hypertension and hemorrhagic shock; and directly contribute to development of clinically effective treatment programs.