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: 3238432
• 负责人: ANTHONY KOO
• 金额: $ 12.03万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3238432
• 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; 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.

大鼠缺血再灌注的病理生理问题