CHRONIC EFFECTS OF HEATING ON TISSUE AND PERFUSION

加热对组织和灌注的慢性影响

• 批准号: 3361591
• 负责人: HIROAKI HARASAKI
• 金额: $ 30.28万
• 依托单位: CLEVELAND CLINIC FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3361591
• 关键词: angiogenesis; blood circulation; body temperature regulation; cellular pathology; complement; cow; electron microscopy; fibroblasts; heart prosthesis; heat; heat injury; hyperthermia; immunity; immunocytochemistry; immunoregulation; implant; inflammation; lung; lung injury; lymphocyte; mathematical model; monocyte; muscle disorders; necrosis; neutrophil; surface property; vascular endothelium; wound healing

The feasibility of totally implantable circulatory support and replacement systems depends on the ability of the body to dissipate the rejected heat from the power source driving the blood pump. The effects of the interfacial temperature of 41 degrees C to 45 degrees C on components involved in host defense, tissue healing and foreign body reaction are, however, largely unknown. Our preliminary in vitro experiments showed temperature dependent suppression of immunocompetent cells and tissue repair cells. Chronic and continuous heat dissipation into the body creates a new biological and medical problem. Recent chronic in vivo experiments in calves implanting heating devices with constant heat fluxes showed persistent inflammatory reaction, thick tissue capsule formation, and necrosis in the tissue capsule itself and adjacent organs at far lower heat fluxes than those previously thought to be acceptable. It was also found that a considerable difference in interface temperature exists between the muscle and lung tissues in dissipating the same amount of heat. In addition, phagocytic, chemotactic, and random migration functions of circulating leukocytes were suppressed in animals which received more than a 0.08W/cm2 heat flux. When the power input was controlled to yield constant heater surface temperature, the heat flux necessary to maintain that temperature increased with time for temperatures above 42 degrees C. This suggested the presence of some heat adaptation mechanism. Still, it is necessary to perform further studies in which tissue temperature and perfusion can be measured in vivo. Concurrently, heat effects on crucial cellular and immune components must be determined. In this way, an analytical model of the tissues' response to heat may be formulated. The specific aims of this proposed program are: (1) to investigate the effects of chronic heating on biological components crucial to systemic and local heat defense, wound healing, and surface interactions; (2) to determine the in vivo temperature distribution response to chronic heat generated by an implanted device, to identify the safe range of high temperature, and the corresponding tissue reactions, and (3) to develop a mathematical model of the tissue temperature distribution which incorporates both long- and short-term adaptation mechanisms to heat through angiogenesis and increased perfusion, respectively. The information obtained in the proposed studies will be invaluable not only for currently ongoing artificial heart programs, but also for future application of chronic hyperthermia for cancer patients.

全植入式循环支持的可行性 更换系统取决于身体消散的能力 驱动血泵的电源排出的热量。 这 41°C 至 45°C 界面温度的影响 C 涉及宿主防御、组织愈合和异物的成分 然而，身体反应很大程度上是未知的。我们的初步体外 实验表明温度依赖性抑制免疫活性 细胞和组织修复细胞。 慢性持续散热 进入体内会产生新的生物和医学问题。 最近的 在小牛身上植入加热装置的慢性体内实验 恒定的热通量显示出持续的炎症反应，浓稠 组织被膜形成，组织被膜本身坏死， 邻近器官的热通量远低于之前认为的 是可以接受的。 还发现差异很大 肌肉和肺组织之间存在界面温度 散发相同量的热量。 此外，吞噬细胞、 循环白细胞的趋化和随机迁移功能 在接受超过 0.08W/cm2 热量的动物中受到抑制 通量。 当控制功率输入以产生恒定的加热器时 表面温度，维持该温度所需的热通量 当温度高于 42 摄氏度时，温度随时间增加。 这表明存在某种热适应机制。 仍然， 有必要进行进一步的研究，其中组织温度 和灌注可以在体内测量。 同时，热效应 必须确定关键的细胞和免疫成分。 在这个 这样，组织对热反应的分析模型可能是 制定的。 本拟议计划的具体目标是：(1) 研究慢性加热对生物成分的影响 对于全身和局部热防御、伤口愈合和表面保护至关重要 互动； (2)确定体内温度分布 对植入设备产生的慢性热量的反应，以识别 高温的安全范围以及相应的组织 反应，以及（3）开发组织的数学模型 温度分布包括长期和短期 通过血管生成和增加对热量的适应机制 分别进行灌注。 拟议中获得的信息 研究不仅对于目前正在进行的人工 心脏计划，也为未来慢性热疗的应用 对于癌症患者。