Direct Peritoneal Resuscitation from Hypovolemic Shock

低血容量休克的直接腹膜复苏

• 批准号: 6754143
• 负责人: Richard N Garrison
• 金额: $ 22.05万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6754143
• 关键词: autoradiography; cytokine; glucose; hemorrhagic shock; hypovolemia; immunologic assay /test; inflammation; intraperitoneal injections; intravital microscopy; laboratory rat; multiple organ failure; neutrophil; resuscitation; saline; vascular endothelium; vasoconstriction; vasodilation

DESCRIPTION (provided by applicant): The pathophysiology of Hemorrhagic shock consists of disruption of the cellular metabolic functions endothelial barrier properties, redistribution of body fluids and electrolytes, a systemic inflammatory response, and a deleterious intestinal vasoconstriction and a disproportionate splanchnic hypoperfusion, which persists even after adequate fluid replacement that restores and maintains hemodynamics. These pathophysiologic events cause local and remote tissue injury that culminates in multiple organ failure (MOF) by mechanisms, which are poorly understood. It is hypothesize that initiation of direct intraperitoneal resuscitation (DPR) with a balanced physiologic salt solution supplemented with glucose (2.5%), at the time of conventional resuscitation (CR) from hemorrhagic shock can reverse the pathophysiology of this syndrome, improving resuscitation outcome, potentially preventing (MOF) and improving survival: a) by suppressing the hemorrhage-induced systemic inflammatory response, b) by direct intestinal resuscitation to enhance visceral perfusion and cardiac output, c) by improving endothelial cell responsiveness, to vasodilators, and d) by preventing the hemorrhage-induced water and electrolytes imbalance. To address this hypothesis, we will utilize intravital microscopy, and quantitative autoradiography (QAR) to perform in vivo studies in a rodent model of hemorrhagic shock, which will be resuscitated with either CR or CR+DPR and determine the following: 1) Serum cytokines profile and level of prostanoid metabolites; 2) Endothelial cell function with dose-response curves to endothelial-dependent, receptor-mediated and non-receptor mediated as well as endothelial-independent agonists; 3) The pattern of distribution of tissue water (intravascular thetaiv, interstitial thetaif, intracellular thetaic) in the gut and abdominal wall with QAR; 4) The role of neutrophils in the derangement of intestinal microvascular endothelium by measuring microvascular responses in the presence of anti-PMN serum and specific antibodies; and 5) The mechanisms involved in the ability of DPR to reverse the pathophysiology of the shock syndrome. Long-term objectives are to develop a pre-clinical protocol that utilizes DPR as a prelude to translation of the results to trauma patients and finally a clinical protocol that utilize DPR to prevent multiple organ failure in hemorrhage shock with resuscitation.

描述（由申请人提供）： 出血性休克的病理生理包括破坏细胞代谢功能的内皮屏障特性，体液和电解质的重新分布，全身性炎症反应以及有害的肠血管血管收缩和不成比例的闪烁性低流性，甚至在后续易位的情况下，还可以很好地恢复液体，并恢复液体液体，以恢复该恢复液体，以恢复该稳定性，以恢复该稳定性，并在该稳固且易于替代。保持血液动力学。这些病理生理事件会导致局部和远程组织损伤通过机制在多器官衰竭（MOF）中达到高潮，而这些机制知之甚少。假设是，在传统的复苏（CR）中，通过均衡的葡萄糖（2.5％）的均衡生理盐溶液开始直接腹膜内复苏（DPR），可以从出血性休克中撤回该综合征的病理生理学，从而改善复苏结果，从而逆转。潜在的预防（MOF）和改善生存率：a）通过抑制出血诱导的全身性炎症反应，b）直接肠道复苏以增强内脏灌注和心脏输出，c）通过提高内皮细胞反应性，对血管舒张剂，以及对血管舒张剂的以及d）防止出血诱导的水和电解质失衡。为了解决这一假设，我们将利用插入式显微镜和定量自身自显影（QAR）在啮齿动物休克的啮齿动物模型中进行体内研究，该模型将用CR或CR+DPR复苏，并确定以下内容：1）血清细胞因子）前列腺素代谢物的剖面和水平； 2）具有剂量反应曲线的内皮细胞功能，可与内皮依赖性，受体介导的和非受体介导的和无依赖性的激动剂； 3）在肠道中的组织水分布（血管内thetaiv，间质thetaif，细胞内thetaic）在肠道和带有QAR的腹壁中的模式； 4）中性粒细胞在存在抗PMN血清和特定抗体的存在下测量微血管反应，在肠道微血管内皮的危险中的作用； 5）DPR能力逆转休克综合征的病理生理能力所涉及的机制。长期目标是开发一种临床前方案，该方案利用DPR作为将结果转化为创伤患者的序幕，最后是一种临床方案，该方案利用DPR来防止随着复苏而进行出血性的多器官衰竭。