Static Magnetic Fields and Microvascular Adaptation

静磁场和微血管适应

• 批准号: 6375442
• 负责人: THOMAS C SKALAK
• 金额: $ 24万
• 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/6375442
• 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.

外周血流量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的基本机制，以及对中风、心肌梗死和创伤的补偿。尽管人们已经集中精力研究磁场在缺血性损伤或创伤后组织存活和恢复中的可能治疗益处，但对体内完整血管网络对磁场应用的反应知之甚少。本研究旨在验证静态磁场诱导完整组织中的小动脉血管扩张，并通过产生应激介导的细胞因子来促进微血管网络的生长的中心假设。长期目标是基于分子机制介导急性血管活性和体内完整微血管网络的慢性重塑，促进理解和优化治疗磁场的设计。研究的具体目的是确定体内骨骼肌完整小动脉网络中动脉血管扩张的位置和时间顺序，以及在有和没有神经阻断、抑制Ca2+- atp酶和抑制一氧化氮合酶的情况下的血流速率；探讨磁场对急性缺血再灌注发作后血流恢复和组织损伤的影响；在正常情况下和慢性或急性血管阻塞后，建立磁场在骨骼肌小动脉重塑和毛细血管生成中的作用；利用原位杂交和PDGF和tgf - β阻断抗体在肠系膜寡妇试验中确定慢性磁场作用下微血管网络中的细胞因子表达是否介导成纤维细胞募集和分化或平滑肌增殖；并利用计算机数学模拟斜方肌微血管网络，验证磁场作用下壁应力改变和血管扩张性扩张在体内急性小动脉反应和长期小动脉模式形成中的作用。这些方法不仅首次展示了静态磁场下的急性小动脉血管扩张，而且这些技术代表了一个创新的实验平台，为在磁场应用过程中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意义的课题。