VASCULAR RESPONSE TO HEMORRHAGE IN PORTAL HYPERTENSION

出血性休克是门静脉高压症最常见、最致命的并发症 高血压（PHT）。PHT患者对大出血耐受性差， 肾功能衰竭的风险很高，成人呼吸道疾病 痛苦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思维的能力 门静脉高压症休克的治疗依赖于更彻底的 了解门脉血管反应。 最近的研究表明，在PHT，门静脉血管系统成为 “高动力”，部分原因是过量的前列环素（PGI 2）， 由肠系膜血管产生的血管扩张剂;以及反应减弱 内源性血管收缩剂（血管紧张素II，精氨酸加压素）。 出血和容量复苏后，门静脉压力实际上 升高至高于基线，重新创建了持续性高血压的风险因素。 流血了我们的实验室最近发现这种异常的血液动力学 PHT对出血/复苏的反应可能是由 内脏静脉和肠系膜动脉的异常反应 血管对血管紧张素II、AVP和PGI 2的影响。 这项建议旨在确定假定的激素与 内脏血流介质：PGI 2、血管紧张素II和精氨酸 血管加压素（AVP）在失血性休克异常血管反应中的作用 在PHT。采用门静脉部分结扎法建立门静脉高压症模型， 胆管结扎兔肝硬化模型，出血， 复苏将在正常和PHT动物中产生， 特异性阻断剂/激动剂。前列腺素和肽水平/作用将 测量以及全身、内脏和门静脉侧支 血流动力学在同一模型中，PGI 2、血管紧张素II和AVP血管 将测定受体。研究以确定 内脏血管对出血的反应， 荷尔蒙的作用将被完成。 这些实验应该能为我们理解 门静脉高压症和失血性休克;并直接有助于 制定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.