EXERCISE--CORONARY RESERVE, CORONARY HEART DISEASE

本研究计划将成年小型猪作为一种 运动训练实验模型(ET)在运动训练研究中的应用 ET诱导的冠脉血管适应性。我们已经确定了外星人 提高冠脉血管床输送营养物质的能力 并从心肌细胞中分离出代谢产物。ET增加两种血液 流量(BF)和毛细管扩散能力。实验 针对特定目标1提出的建议旨在确定是否由ET诱导 冠状动脉运输能力的增加是由于大小和/或 血管数量(即血管生成)和/或改变对BF和 它的分布。形态测量技术将被用来测量 微血管数量和大小及估计毛细血管交换 这一领域为血管生成假说提供了明确的检验。至 评估改变的高炉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。总计 和局部(微球)冠状动脉血流量、毛细血管扩散量 (多指标稀释技术)和全身血流动力学 在体内测量，在BF自动调节完好和在最大限度 血管扩张。运输数据将通过模型分析进行解释 使用可用的模型和冠脉传输的模型 正在开发中。我们还证明了ET改变了固有的 冠状动脉的收缩行为。结果表明， ET冠脉兴奋收缩偶联改变 猪。为Aim 2概述的实验将使用分离的片段 冠状动脉测试ET改变内皮的假说 血管平滑肌张力和/或受体的中介调控 介导对VSM细胞的控制。为目标#3描述的实验 将使用分离的内皮细胞(EC)和VSM细胞来测试 ET改变心肌细胞内钙离子(CaI)调节的假说 冠状内皮细胞和/或VSM细胞。用Fura-2测量CAI 微量荧光法。初步数据显示，蔡铭超的控制力是 ET猪Aim 4冠状动脉EC和VSM的改变 确定这些ET诱导的冠状动脉适应是否仅限于 大的心外膜动脉或也存在于小动脉，近 阻力大小的动脉和小动脉。看起来这项运动 训练诱导的冠状动脉血管适应包括：血管生成， 改变的神经体液控制机制和内在的改变 冠状动脉的收缩特性。 完成拟议的研究将提供一个全面的 对运动性冠状动脉病变相关机制的认识 血管适应性，并可提供必要的信息 了解ET在预防和/或治疗中的明显有效性 治疗冠心病。

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.