EXERCISE--CORONARY RESERVE, CORONARY HEART DISEASE

锻炼——冠状动脉储备、冠心病

• 批准号: 3351563
• 负责人: M HAROLD LAUGHLIN
• 金额: $ 24.85万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-15 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3351563
• 关键词: acetylcholine; biological transport; caffeine; calcium transporting ATPase; cardiovascular disorder prevention; coronary artery; coronary disorder; coronary vasodilator; dipyridamole; dogs; exercise; heart cell; heart circulation; heart contraction; heart pharmacology; indicator dilution test; miniature swine; myocardial ischemia /hypoxia; myocardium; oxygen transport; papaverine; radiotracer; training; vascular endothelium permeability; vascular smooth muscle; vasoactive agent; voltage gated channel

This research program has developed the adult miniature swine as an experimental model of exercise training (ET) for use in the study of ET-induced coronary vascular adaptation. We have established that ET improves the capacity of the coronary vascular bed to transport nutrients to and metabolites away from cardiac myocytes. ET increases both blood flow (BF) capacity and capillary diffusion capacity. Experiments proposed for Specific Aim 1 are designed to determine if ET-induced increases in coronary transport capacity are due to increased size and/or numbers of vessels (ie, angiogenesis) and/or to altered control of BF and its distribution. Morphometric techniques will be used to measure microvascular vessel numbers and size and to estimate capillary exchange area to provide a definitive test of the angiogenesis hypothesis. To evaluate the role of altered control of BF and its distribution, a uniquely complete set of coronary transport data will be obtained. Total and regional (microspheres) coronary BF, capillary diffusion capacity (multiple-indicator dilution technique), and systemic hemodynamics will be measured in-vivo with BF autoregulation intact and during maximal vasodilation. Transport data will be interpreted with model analysis employing available models and models of coronary transport that are being developed. We have also demonstrated that ET alters the intrinsic contractile behavior of coronary arteries. Results indicate that excitation-contraction coupling is altered in coronary arteries of ET pigs. Experiments outlined for Aim 2 will use isolated segments of coronary arteries to test the hypotheses that ET alters endothelium mediated control of vascular smooth muscle (VSM) tone and/or receptor mediated control of VSM cells. The experiments described for Aim # 3 will use isolated endothelial cells (EC) and VSM cells to test the hypothesis that ET alters the regulation of intra-cellular Ca++ (Cai) in coronary ECs and/or VSM cells. Cai will be measured with fura-2 microfluorimetry. Preliminary data indicate that the control of Cai is altered in both EC's and VSM of coronary arteries from ET pigs Aim 4 will determine if these ET-induced coronary adaptations are restricted to large epicardial arteries or also present in small arteries, near resistance sized arteries and arterioles. It appears that exercise training-induced coronary vascular adaptation involves: angiogenesis, altered neurohumoral control mechanisms and changes in the intrinsic contractile characteristics of coronary arteries. Completion of the proposed research will provide a comprehensive understanding of the mechanisms involved in training-induced coronary vascular adaptation and may provide information necessary for understanding the apparent effectiveness of ET in prevention and/or treatment of coronary disease.

该研究计划开发了成年小型猪作为 用于研究的运动训练（ET）实验模型 ET 诱导的冠状血管适应。 我们已经确定 ET 提高冠状血管床输送营养物质的能力 进入心肌细胞并代谢远离心肌细胞。 ET 增加双血 流动（BF）能力和毛细管扩散能力。 实验 针对具体目标 1 提出的建议旨在确定是否由 ET 引起 冠状动脉转运能力的增加是由于尺寸的增加和/或 血管数量（即血管生成）和/或改变 BF 和 它的分布。 将使用形态测量技术来测量 微血管数量和大小并估计毛细血管交换 区域提供血管生成假说的明确检验。 到 评估改变 BF 控制及其分布的作用，a 将获得唯一完整的冠状动脉传输数据集。 全部的 和局部（微球）冠状动脉 BF、毛细血管扩散能力 （多指标稀释技术），全身血流动力学将 在 BF 自动调节完好无损的情况下进行体内测量，并在最大 血管舒张。 将通过模型分析来解释运输数据 采用可用的模型和冠状动脉运输模型 正在开发中。 我们还证明了 ET 改变了内在的 冠状动脉的收缩行为。 结果表明 ET 冠状动脉的兴奋-收缩耦合发生改变 猪。 目标 2 概述的实验将使用孤立的片段 冠状动脉以检验 ET 改变内皮的假设 血管平滑肌 (VSM) 张力和/或受体的介导控制 VSM 细胞的介导控制。 目标#3 描述的实验 将使用分离的内皮细胞（EC）和VSM细胞来测试 假设 ET 改变细胞内 Ca++ (Cai) 的调节 冠状动脉 EC 和/或 VSM 细胞。 Cai将用fura-2进行测量 微荧光测定法。初步数据显示，蔡某的控制权是 ET 猪冠状动脉的 EC 和 VSM 均发生改变，目标 4 将 确定这些 ET 诱导的冠状动脉适应性是否仅限于 大心外膜动脉或也存在于小动脉中，靠近 阻力大小的动脉和小动脉。 看来锻炼 训练引起的冠状血管适应包括：血管生成， 改变神经体液控制机制和内在的变化 冠状动脉的收缩特性。 完成拟议的研究将提供全面的 了解训练诱发冠状动脉的机制 血管适应，并可能提供必要的信息 了解 ET 在预防和/或 治疗冠心病。