Static Magnetic Fields and Microvascular Adaptation

静磁场和微血管适应

• 批准号: 6323965
• 负责人: THOMAS C SKALAK
• 金额: $ 23.8万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6323965
• 关键词: alternative medicine; calcium transporting ATPase; computer simulation; fibroblasts; in situ hybridization; laboratory rat; magnetic field; nitric oxide synthase; platelet derived growth factor; transforming growth factors; vasodilation

Acute regulation of peripheral blood flow and long-term microvascular remodeling play central roles in vascular biology because they are essential mechanisms enabling normal vascular adaptation in exercise and would healing, as well as compensation for stroke, myocardial infarction, and trauma. Despite intensive effort that has been focused on possible therapeutic benefits of magnetic fields in tissue survival and recovery following ischemic insult or trauma, little is known of the response of intact blood vessel networks to application of magnetic fields in vivo. This study is designed to test the central hypotheses that static magnetic fields induce arteriolar vasodilation in intact tissues and enhance the growth of microvascular networks via the production of stress-mediated cytokines. The long-term objective is to advance understanding and optimize the design of therapeutic magnetic fields based on the molecular mechanisms mediating acute vasoactivity and chronic remodeling of complete microvascular networks in vivo. The specific aims of the research are to determine the sites and time sequence of arteriolar vasodilation and blood flow rate in intact arteriolar networks of skeletal muscle in vivo, with and without neural blockade, inhibition of Ca2+-ATPase, and inhibition of nitric oxide synthase; to establish the efficacy of magnetic field application on recovery of blood flow and reduction of tissue injury after acute ischemia/reperfusion episodes; to establish the role of magnetic fields in arteriolar remodeling and capillary angiogenesis in skeletal muscle in vivo, both under normal conditions and after chronic or acute vascular obstruction; to determine whether fibroblast recruitment and differentiation or smooth muscle proliferation is mediated by cytokine expression in the microvascular network during chronic application of magnetic fields using in situ hybridization and blocking antibodies to PDGF and TGF-beta in a mesenteric widow assay; and to use a mathematical computer simulation of the microvascular network of spinotrapezius muscle to test the roles of altered wall stresses and propagated vasodilation in the acute arteriolar response and long-term arteriolar pattern formation during magnetic field application in vivo. Not only have these methods provided the first demonstration of acute arteriolar vasodilation in a static magnetic field, but the techniques represent an innovative experimental platform that opens the way for in vivo study of molecular regulation of microvascular network adaptation during magnetic field application, a subject of vast therapeutic importance.

外周血流的急性调节和长期微血管重塑在血管生物学中发挥着核心作用，因为它们是运动中正常血管适应和愈合以及中风、心肌梗死和创伤代偿的重要机制。 尽管人们集中精力研究磁场对缺血性损伤或创伤后组织存活和恢复的可能治疗益处，但对完整血管网络对体内磁场应用的反应知之甚少。 本研究旨在测试静磁场诱导完整组织中的小动脉血管舒张并通过产生应激介导的细胞因子来增强微血管网络的生长的中心假设。 长期目标是基于介导体内完整微血管网络的急性血管活动和慢性重塑的分子机制，促进对治疗磁场的理解和优化设计。该研究的具体目的是确定体内骨骼肌完整小动脉网络中小动脉血管舒张和血流速率的位点和时间顺序，有或没有神经阻滞、Ca2+-ATP酶抑制和一氧化氮合酶抑制；确定磁场应用对急性缺血/再灌注后血流恢复和组织损伤减少的功效；确定磁场在体内骨骼肌小动脉重塑和毛细血管生成中的作用，无论是在正常条件下还是在慢性或急性血管阻塞后；确定在长期施加磁场期间，成纤维细胞募集和分化或平滑肌增殖是否由微血管网络中的细胞因子表达介导，在肠系膜寡妇测定中使用原位杂交和PDGF和TGF-β阻断抗体；并使用斜方肌微血管网络的数学计算机模拟来测试改变的壁应力和传播的血管舒张在体内磁场应用期间的急性小动脉反应和长期小动脉模式形成中的作用。 这些方法不仅首次证明了静磁场中的急性小动脉血管舒张，而且这些技术代表了一个创新的实验平台，为磁场应用期间微血管网络适应的分子调节的体内研究开辟了道路，这是一个具有巨大治疗重要性的课题。