Effect of blood flow pattern on endothelial damage

描述(申请人提供)：我们的长期目标是确定改善人类血管内皮功能的最佳血流模式。我们增强内皮扩张功能的方法将利用重复收缩过程中肌肉收缩与血流的相互作用。由此产生的振荡血流模式对内皮细胞施加剪切力，并可能导致损伤。这项拟议的研究旨在验证以下假设：产生最大幅度血流振荡的肌肉收缩会导致最大程度的内皮损伤，以及不同血流模式下的运动训练将不同程度地改善内皮扩张功能。在重复的动态前臂肌肉收缩中，不同的肌肉收缩占空比和张力发展将产生不同的血流模式，并将通过测量血浆中von Willebrand因子的浓度来评估内皮损伤。握力训练将在不同的血流模式下进行(大的血流振荡和大的逆流)。内皮扩张功能将通过测量峰值反应性充血和舌下含服硝酸甘油来评估。这项拟议的研究将促进人们对体育活动如何改善血管健康的了解，并可能导致开发一种有效的运动干预措施，旨在改善人类的内皮依赖性扩张器功能。

DESCRIPTION (provided by applicant): Our long-term goal is to characterize the optimal blood flow pattern for improving vascular endothelial function in humans. Our approach to enhance endothelial dilatory function will utilize the muscle contraction-blood flow interaction during repeated contractions. The resulting oscillatory blood flow pattern places shear stress on the endothelium and may result in injury. The proposed research aims to test the hypotheses that muscle contractions producing blood flow oscillations of the largest amplitude will result in the most injury to the endothelium, and that exercise training at different blood flow patterns will differentially improve endothelial dilatory function. Different blood flow patterns will be generated by varying muscle contraction duty cycle and tension development during repeated dynamic forearm muscle contractions, and endothelial damage will be assessed by measuring plasma concentrations of von Willebrand Factor. Handgrip exercise training will be performed at different blood flow patterns (large flow oscillations vs. large retrograde flow). Endothelial dilatory function will be assessed by measuring peak reactive hyperemia and sublingual administration of nitroglycerin. The proposed research will advance knowledge of how physical activity may improve vascular health, and may lead to the development of an effective exercise intervention aimed at improving endothelial-dependent dilator function in humans.