Effect of blood flow pattern on endothelial damage

描述（由申请人提供）：我们的长期目标是表征改善人体血管内皮功能的最佳血流模式。我们的方法，以提高内皮舒张功能将利用肌肉收缩血流相互作用在反复收缩。产生的振荡血流模式在内皮上施加剪切应力，并可能导致损伤。该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将导致对内皮的最大损伤，并且在不同血流模式下进行运动训练将差异性地改善内皮舒张功能。通过在反复动态前臂肌肉收缩期间改变肌肉收缩占空比和张力发展来产生不同的血流模式，并通过测量血管性血友病因子的血浆浓度来评估内皮损伤。将在不同的血流模式（大流量振荡与大逆行流量）下进行握力运动训练。通过测量峰值反应性充血和舌下含服硝酸甘油来评估内皮舒张功能。这项拟议的研究将推进体力活动如何改善血管健康的知识，并可能导致开发一种有效的运动干预，旨在改善人类内皮依赖性扩张功能。

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.