BLOOD FLOW IN THE DENERVATED ISCHEMIC REPERFUSED LIVER

去神经缺血再灌注肝脏中的血流

• 批准号: 3238436
• 负责人: ANTHONY KOO
• 金额: $ 15.67万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3238436
• 关键词: blood cell count; cell adhesion; denervation; erythrocytes; fluorescence microscopy; fluorescent dye /probe; free radicals; hemorrhagic shock; laboratory rat; leukocytes; liver circulation; liver circulation disorder; liver ischemia /hypoxia; liver transplantation; membrane proteins; microcirculation; monoclonal antibody; platelet aggregation; reperfusion; vascular endothelium

The pathophysiological problem of ischemia and reperfusion in the liver is clinically encountered in liver transplanation and in hemorrhagic shock. In liver transplantation, the donor liver is denervated and non-perfused by blood (an ischemic organ), but it is reperfused after the surgical anastomosis of blood vessels has been completed. Similarly, in shock the liver is ischemic, and reperfusion occurs when the systemic hypotension is corrected. In many vascular beds, reperfusion after a period of ischemia only results in a transient return of blood flow (the "no reflow" phenonemon). We hypothesize that ischemia and reperfusion in the liver also results in a no reflow situation. In addition, we hypothesize that denervation further decreases the extent and duration of perfusion in the liver microcirculation. Hitherto, these studies in the liver have not been performed at the microcirculatory level. We propose inducing ischemia and reperfusion in the rat liver by clamping and unclamping the hepatic vessels. We propose using in vivo bright-field and fluorescent video microscopic methods to observe and quantitate the microcirculatory disturbances leading to the no reflow phenomenon. In particular, we shall measure erthrocyte velocity and flux, and microcirculatory hematocrit in the liver sinusoid. We shall use acridine orange (a fluorochrome) to label the leukocytes in vivo, and measure the leukocyte velocity and the incidence of leukocyte plugging in liver sinusoids. We shall also infuse close intravascularly hypoxanthine and xanthine oxidase to generate oxygen-derived free radicals in the liver microcirculation. By using monoclonal antibodies which recognize the leukocyte membrane glycoproteins and thus inhibit leukocyte adherence to the endothelial wall, and using scavengers to inhibit the action of free radicals, we propose to evaluate the mechanism underlying the microcirculatory disturbance in ischemia and reperfusion. The aims are, in the rat liver subjected to ischemia and reperfusion, (a) to examine the microcirculatory disturbances and to elucidate the nature and cause of these disturbances, (b) to determine the microcirculatory alterations in hepatic autonomic denervations, (c) to determine the role of leukocyte-endothelium adhesion, and/or intravascular platelet aggregation, in the microcirculatory disturbances, and (d) to determine the of free radicals in the microcirculatory disturbances.

脑缺血再灌注的病理生理学问题 肝脏是临床上遇到的肝移植和 失血性休克 在肝移植中，供体肝脏是 失神经和非血液灌注（缺血器官），但它 是在血管吻合手术后再灌注的， 完成了 类似地，在休克时，肝脏缺血， 当全身性低血压被纠正时，发生再灌注。 在 许多血管床，仅在缺血一段时间后再灌注 导致血液流动的短暂回流（“无回流”）， phenonemon）。 我们假设缺血和再灌注在 肝脏也导致无回流的情况。 另外我们 假设去神经支配进一步降低了 肝脏微循环灌注持续时间。 到目前为止， 这些肝脏研究尚未在 微循环水平。 我们建议诱导缺血， 在大鼠肝脏再灌注通过夹紧和松开 肝血管 我们建议使用体内亮场和 荧光视频显微镜法观察定量 导致无复流的微循环障碍 现象 特别是，我们将测量红细胞速度 和流量以及肝窦内的微循环血细胞比容。 我们将使用吖啶橙子（一种荧光染料）标记 体内白细胞，并测量白细胞速度和 肝血窦中白细胞堵塞的发生率。 我们亦会 封闭式血管内注入次黄嘌呤和黄嘌呤氧化酶， 在肝脏中产生氧自由基 微循环 通过使用单克隆抗体， 从而抑制白细胞 粘附于内皮壁，并使用清除剂来抑制 自由基的作用，我们建议评估的机制 缺血时微循环障碍的基础， 再灌注 目的是，在大鼠肝脏缺血后， 和再灌注，（a）检查微循环障碍 并阐明这些干扰的性质和原因，（B） 确定肝自主神经微循环的改变 去神经，（c）确定白细胞内皮细胞的作用 粘附和/或血管内血小板聚集 微循环障碍，和（d）以确定自由的 自由基在微循环障碍。