CORONARY OCCLUSION--COLLATERAL ARTERY FUNCTION

缺血性心脏病是最常见的严重健康问题 当代西方社会的一部分。一种重要的自然防御机制 患心脏病的心脏是侧支循环，它增加了 心肌缺血和心肌损伤对结构和功能的影响 缺氧。然而，侧支动脉的血管运动特性是 难以直接使用患者和完整的实验进行评估 伴随非侧支血管和心肌的模型 变更可能会使对主要抵押品的解释复杂化 回应。因此，我们通过体外实验解决了这个问题。 高血压病患者血管平滑肌及内皮功能的分析 从活体侧支模型中分离出的侧支动脉 发展。目前的项目是基于总体假设 冠状动脉平滑肌和血管内皮细胞的内在功能 在进行性冠状动脉闭塞和慢性冠脉闭塞后发生改变 侧支循环；然而，功能改变是依赖的。 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 假设特定的膜离子传输机制 细胞内钙离子调节受侧支变化的影响。 我们的初步研究提供了证据证明 侧支对内皮素和前列腺素F2α的血管收缩反应 并改变侧支循环和受体的内皮介导的松弛 (侧支依赖动脉。当前项目的具体目标 涉及以下方面的体外评价：1)受体介导的(内皮素， PGF2pha)和选定的非受体钙依赖(咖啡因，[Ca]， 佛波酯、兰诺定)侧支血管舒缩干预；2)VSM 膜离子转运与细胞内钙离子浓度([Ca~(2+)]i) 与血管收缩反应性改变相关的变化 络脉；3)内皮依赖和非内皮依赖性的松弛 络脉和络脉依赖动脉的反应和[Ca~(2+)]i； 4)冠脉和冠脉内皮细胞依赖性反应 侧支动脉在缺氧的情况下存在。终点为 测量包括：等长收缩(管道和微血管)； 微血管尺寸(视频跟踪成像技术).放射性同位素 通量(42K，45Ca)和[Ca+]i(Fura-2微量荧光法)。这些 研究旨在确定潜在的病理生理机制。 冠脉闭塞和慢性侧支循环灌注改变 冠状动脉血管的内在收缩和松弛特性。 所获得的信息将有助于药物治疗的发展 优化闭塞后侧支循环血流的策略 心肌与心肌梗死前、冠状动脉狭窄的治疗 疾病。

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.