CORONARY OCCLUSION--COLLATERAL ARTERY FUNCTION

冠状动脉闭塞--侧支动脉功能

• 批准号: 3366960
• 负责人: JANET L PARKER
• 金额: $ 21.02万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3366960
• 关键词: caffeine; collateral circulation; coronary artery; coronary disorder; coronary occlusion /thrombosis; dogs; endothelin; heart circulation; heart contraction; heart pharmacology; ion transport; muscle relaxation; myocardial ischemia /hypoxia; phorbols; prostaglandin F; receptor; ryanodine; vascular smooth muscle; vasoconstrictors; vasomotion

Ischemic heart disease represents the most common serious health problem of contemporary western society. An important natural defense mechanism of the diseased heart is the collateral circulation, which increases in structure and function under the influence of myocardial ischemia and hypoxia. However, vasomotor properties of collateral arteries are difficult to evaluate directly using patients and intact experimental models where concomitant non-collateral vascular and myocardial alterations may complicate interpretation of primary collateral responses. Therefore, we have approached this problem using in vitro analyses of vascular smooth muscle (VSM) and endothelium function of collateral arteries isolated from in vivo models of collateral development. The current project is based on the overall hypothesis that intrinsic function or coronary artery smooth muscle and endothelium is altered following progressive coronary occlusion and chronic collateral perfusion; the functional alterations, however, are dependent on vascular site (donor; collateral; recipient) and on artery size (conduit; near-resistance microvessel; resistance arteriole). We also postulate that specific membrane ion transport mechanisms subserving intracellular Ca2+ regulation are subject to alteration in collaterals. Our preliminary studies have provided evidence for impaired vasoconstrictor responses of collaterals to endothelin and PGF2alpha, and altered endothelium-mediated relaxation in collateral and recipient (collateral-dependent arteries. Specific aims of the current project involve in vitro evaluation of: 1) receptor-mediated (endothelin, PGF2alpha) and selected non-receptor Ca2+-dependent (caffeine, [Ca], phorbol ester, ryanodine) vasomotor interventions in collaterals; 2) VSM membrane ion transport and intracellular Ca2+ concentration ([Ca2+]i) changes associated with altered vasoconstrictor responsiveness of collaterals; 3) endothelium-dependent and-independent relaxation responses and [Ca2+]i in collaterals and collateral-dependent arteries; and 4) smooth muscle and endothelium-dependent responses of coronary and collateral arteries in the presence of hypoxia. End points to be measured include: isometric contraction (conduit and microvessel); microvessel dimensions (video tracking imaging techniques); radioisotope fluxes (42K, 45Ca); and [Ca2+]i (fura-2 microfluorometry). These studies are designed to identify potential pathophysiological mechanisms whereby coronary occlusion and chronic collateral perfusion alter intrinsic contraction and relaxation properties of coronary vasculature. Information gained will aid in the development of pharmacotherapeutic strategies for optimizing collateral blood flow to post-occlusive myocardium and treatment of preinfarction, stenotic coronary artery disease.

缺血性心脏病是最常见的严重健康问题 当代西方社会。 一种重要的自然防御机制 病变心脏的侧支循环， 结构和功能的影响下，心肌缺血和 缺氧 然而，侧支动脉的血管扩张特性 难以直接使用患者和完整的实验进行评价 伴随非侧支血管和心肌 改变可能使原发侧支病变的解释复杂化 应答 因此，我们已经接近这个问题，使用在体外 血管平滑肌（VSM）和内皮功能分析 从侧支的体内模型中分离的侧支动脉 发展 目前的项目是基于总体假设 冠状动脉平滑肌和内皮的内在功能 在进行性冠状动脉闭塞和慢性 侧支灌注;然而，功能改变依赖于 血管部位（供体;侧支;受体）和动脉大小 （导管;近阻力微血管;阻力小动脉）。 我们也 假设特定的膜离子转运机制 细胞内Ca 2+调节受到侧枝改变的影响。 我们的初步研究提供了证据， 侧支血管对内皮素和PGF 2 α的收缩反应， 并改变了血管和受体的内皮介导的舒张功能 （侧支依赖性动脉。 当前项目的具体目标 包括体外评价：1）受体介导（内皮素， PGF 2 α）和选定的非受体Ca 2+依赖性（咖啡因，[Ca]， 佛波酯、兰尼定）对侧支血管的干预; 2）VSM 膜离子转运和细胞内Ca 2+浓度（[Ca 2 +]i） 与血管收缩反应性改变相关的变化 血管内皮依赖性和非依赖性舒张 侧支和侧支依赖性动脉的反应和[Ca 2 +]i; （4）冠状动脉平滑肌和内皮依赖性反应， 侧支动脉缺氧的情况下。 终点为 测量内容包括：等长收缩（导管和微血管）; 微血管尺寸（视频跟踪成像技术）;放射性同位素 [Ca ~（2+）]i（Fura-2显微荧光法）。 这些 研究旨在确定潜在的病理生理机制 从而使冠状动脉闭塞和慢性侧支灌注改变 冠状动脉血管的固有收缩和舒张特性。 所获得的信息将有助于发展药学 优化闭塞后侧支血流的策略 心肌梗死前、冠状动脉狭窄的治疗 疾病