CHRONIC EFFECTS OF HEATING ON TISSUE AND PERFUSION

全植入性循环支持的可行性 替代系统取决于身体驱散 从驱动血泵的电源中排出热量。这个 41摄氏度至45摄氏度界面温度的影响 C关于参与宿主防御、组织修复和异物的成分 然而，身体反应在很大程度上是未知的。我们初步的体外试验 实验表明，免疫活性受到温度依赖的抑制 细胞和组织修复细胞。慢性持续散热 进入人体内会产生新的生物和医学问题。近期 在小牛体内长期植入加温装置的实验 恒定热流显示持续性炎症反应，厚重 组织包膜的形成和组织包膜本身的坏死 相邻器官的热流密度比之前认为的要低得多 才能被接受。研究还发现，在这方面有相当大的差异 肌肉和肺组织之间存在界面温度 散失同样数量的热量。此外，吞噬功能， 循环白细胞的趋化和随机迁移功能 在受热超过0.08W/cm2的动物体内被抑制 流量。当功率输入被控制为产量恒定加热器时 表面温度，维持这一温度所需的热流 在42摄氏度以上，温度随着时间的推移而升高。 这表明存在一定的热适应机制。不过， 有必要进行进一步的研究，其中组织温度 血流灌注可以在活体内测量。同时，热效应对 必须确定关键的细胞和免疫成分。在这 因此，组织对热的反应的分析模型可能是 公式化的。这项拟议方案的具体目标是：(1) 慢性加温对人体生物成分的影响 对全身和局部的热防御、伤口愈合和表面至关重要 相互作用；(2)测定体内温度分布 对植入设备产生的慢性热的反应，以识别 高温的安全范围，以及相应的组织 反应，以及(3)建立组织的数学模型 同时包含长期和短期的温度分布 热适应机制通过血管生成和增强 分别灌流。在建议中取得的资料 研究将是无价的，不仅对目前正在进行的人工 心脏计划，也为未来慢性热疗的应用 为癌症患者准备的。

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.