GASTRIC BLOOD FLOW AND ACUTE ULCEROGENESIS

胃血流和急性溃疡形成

• 批准号: 2139521
• 负责人: LAURENCE Y CHEUNG
• 金额: $ 20.64万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 1995-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2139521
• 关键词: adenosine; aspirin; disease /disorder model; dogs; ethanol; flame photometry; gastric mucosa; gastritis; gastrointestinal circulation; gastrointestinal disorder diagnosis; gastrointestinal hemorrhage; granulocyte; histamine; hydrogen; ischemia; isoproterenol; leukotrienes; platelet activating factor; potentiometry; prostaglandins; radiotracer; ulcer; vascular endothelium permeability; vascular resistance; vasodilators

Superficial erosive gastritis may account for as much as 40% of upper gastrointestinal bleeding episodes. In most instances, bleeding from thee acute gastric erosions is related to the excessive use of salicylate- containing compounds or alcohol. Exposure of the gastric mucosa to luminal aspirin or alcohol results in a significant increase in gastric mucosal blood flow (GMBF) as measured to the entire stomach or a large segment of the stomach. The increase in GMBF is interpreted as a compensatory response of the stomach to acid or chemical injury. However, when GMBF to the site of erosion formation is measured, focal mucosal ischemia has been demonstrated. To further define the role of GMBF in acute gastric mucosal ulcerogenesis, the proposed studies are designed to 1) determine the mediator or the vasodilator responsible for this overall increase in GMBFk, 2) characterize the microcirculatory changes that result in focal ischemia and, 3) examine factors that may protect against focal ischemia. These studies will utilize an ex vivo mechanically-perfused segment of the dog's stomach. The first goal will be pursued by determining the time course of changes in gastric vascular resistance following mucosal exposure to ethanol and salicylates. These studies will use competitive antagonists and synthesis inhibitors to assess the role of endogenous histamine, adenosine, and prostaglandins as mediators of the overall increase in GMBF during injury. The second aim will be achieved by identifying microvascular events associated with the development of focal mucosal ischemia. In this regard these experiments will determine the relative significance of effects of leukotrienes, proulcerogenic actions of platelet activating factor, involvement of granulocytes in capillary obstruction, and changes in vascular permeability resulting in edema development. The last objective will be accomplished by assessing the protective effect of factors which reduce the severity of focal mucosal ischemia. Several vasodilators such as adenosine analogues, prostaglandins, and isoproterenol will be tested for the degree of protection against focal ischemia and salicylate or ethanol-induced ulcers. These proposed studies will provide new insight into the patho-physiology of acute gastric ulcers. Clinical application of such knowledge may be beneficial in the prevention and treatment of superficial erosive diseases of the gastric mucosa.

表面侵蚀性胃炎可能占上部的40％ 胃肠道出血发作。 在大多数情况下，从你流血 急性胃腐蚀与水杨酸盐过量使用有关 含有化合物或酒精。 胃粘膜暴露于腔内 阿司匹林或酒精会显着增加胃粘膜 血流（GMBF），如整个胃或大部分的测量 胃。 GMBF的增加被解释为补偿性 胃对酸或化学损伤的反应。 但是，当GMBF到 测量了侵蚀的部位，局灶性粘膜缺血一直是 证明。 进一步定义GMBF在急性胃粘膜中的作用 溃疡发生，拟议的研究设计为1）确定 调解人或负责GMBFK总体增加的血管扩张器， 2）表征导致局灶性缺血的微循环变化 3）检查可能预防局灶性缺血的因素。 这些 研究将利用该狗的机械化段 胃。 第一个目标将通过确定变化的时间过程来实现 粘膜暴露于乙醇和 水杨酸盐。 这些研究将使用竞争性拮抗剂和合成 评估内源性组胺，腺苷和 前列腺素是受伤期间GMBF总体增加的介体。 第二个目标将通过识别微血管事件来实现 与局灶性粘膜缺血的发展有关。 在这方面 这些实验将确定影响的相对意义 白三烯，血小板激活因子的探测作用， 粒细胞参与毛细管阻塞和变化 血管通透性导致水肿发育。 最后一个目标将通过评估保护效果来实现 减少局灶性缺血严重程度的因素。 一些 血管扩张剂，例如腺苷类似物，前列腺素和异丙肾上腺素 将测试针对局灶性缺血的保护程度和 水杨酸酯或乙醇引起的溃疡。 这些拟议的研究将为病情生理学提供新的见解 急性胃溃疡。 这种知识的临床应用可能是 有益于预防和治疗表面侵蚀性疾病 胃粘膜。