ENDOTHELIAL FACTORS ON GASTRIC MICROCIRCULATION

最近的研究表明，血管内皮细胞在 通过产生几种物质来调节微循环 血管活性物质，包括血管扩张剂，如一氧化氮和 前列环素，以及内皮素-1等收缩因子。变更生产 在这些内皮衍生因子中，已被假设为启动 事件在微循环功能障碍中，并可能代表潜在的 在各种临床环境中引起多器官损伤。这个 拟议研究的目标是检查 这些内皮衍生因子在胃微循环中的作用 各种情况。拟研究的条件包括：1) 生理条件，2)补体C5a和FMLP的应用 (甲酰-亮氨基-甲硫基-苯丙氨酸)能激活循环 白细胞，已知在脓毒症期间会发生的一种情况，以及3) 缺血/再灌流，低血压和休克的后果， 由于自由基的产生而导致内皮细胞损伤。这些 研究将利用体外机械灌流的节段 狗的胃。组织和血液中前列环素和前列腺素水平的变化 内皮素-1将通过酶免疫分析法检测，一氧化氮 在上述实验条件下，采用微电极技术。 胃微血管损伤也将通过血管的变化来评估 对血浆蛋白、血管阻力、白细胞的通透性 粘附性，和自由基生成。 我们假设这些化合物的合成存在反馈调节。 正常情况下的内皮衍生因子。这些反馈 胃微循环保护作用机制的研究进展 血管通透性和血管阻力对 血管活性物质。然而，这种正常的反馈机制可能是 白细胞或自由基依赖的内皮细胞受损 损伤，如在败血症和休克等临床环境中发生的损伤。 对这一应用的拟议研究将提供新的信息 关于内皮衍生因子在血管内皮细胞瘤发生发展中的作用 胃微血管损伤--胃粘膜的始动事件 受伤。因为胃是严重影响人体健康的器官之一。 有休克、脓毒症和多器官衰竭的患者， 了解胃微循环的变化应该是有益的 据我们对其他器官功能障碍的了解。

Recent studies have shown that endothelial cells play an active role in the regulation of the microcirculation through production of several vasoactive substances, including vasodilators such as nitric oxide and prostacyclin, and constrictors such as endothelin-1. Altered production of these endothelial-derived factors has been postulated as an initiating event in microcirculatory dysfunction, and may represent an underlying cause of multiple organ injury in a variety of clinical settings. The goal of the proposed studies is to examine the formation and actions of these endothelial-derived factors in the gastric microcirculation under various conditions. The conditions to be studied include: 1) physiological conditions, 2) administration of complement C5a and FMLP (formyl-leucyl-methionyl-phenylalanine) which activate circulating leukocytes, a condition known to occur during sepsis, and 3) ischemia/reperfusion, a consequence of hypotension and shock, which causes endothelial cell injury due to free radical generation. These studies will utilize an ex vivo mechanically-perfused segment of the dog's stomach. Changes in tissue and blood levels of prostacyclin and endothelin-1 will be measured by enzyme immunoassays, and nitric oxide by a microelectrode technique under the above experimental conditions. Gastric microvascular injury will also be assessed by changes in vascular permeability to plasma proteins, vascular resistance, leukocyte adherence, and free radical generation. We postulate that there is a feedback regulation of synthesis of these endothelial-derived factors under normal conditions. These feedback mechanisms protect the gastric microcirculation by attenuating changes in vascular permeability and vascular resistance in response to vasoactive agents. However, this normal feedback mechanism may be impaired following leukocyte- or free radical-dependent endothelial injury, as occurs in clinical settings such as sepsis and shock. The proposed studies of this application will provide new information regarding the role of endothelial-derived factors in the development of gastric microvascular injury, an initiating event in gastric mucosal injury. Since the stomach is one of the organs adversely affected in patients with shock, sepsis, and multiple organ failure, a better understanding of gastric microcirculatory changes should be beneficial to our knowledge regarding other organ dysfunctions.