EFFECTS OF COLD ON ACCLIMATION TO HYPOXIA

急性(7天)对血液学、心肺和生化的影响 慢性(14周)暴露于低氧(T=22℃，P02=80托)，寒冷 (Ta=5C，P02=133Torr)和冷+低氧(Ta=5Ca，P02=80Torr) 在豚鼠(Cavia Porcellus)中进行了研究。一组对照动物 将在丹佛我们实验室的环境条件下进行研究 (Ta=22C，PO2=133Torr)。拟议的研究旨在复制 最近报道的观察结果表明，寒冷会削弱血液系统的反应 低氧，并了解参与控制和 调节血液学对这些环境压力的反应。这个 具体目标包括：a)确定时间进程和规模 用体外促红细胞生成素生物测定法测定循环促红细胞生成素的变化； B)通过测量红细胞压积和红细胞压积来评估红细胞生成反应 以及通过检查测定红细胞质量和血浆体积。 通过对组织和整体中的血细胞类型进行计数 血液；c)评估其他因素，即儿茶酚胺、生长和 甲状腺激素、睾酮、铁摄取和储存部位以及红细胞 可能影响红细胞增多症水平的存活率；d)评估 通过测量动脉和静脉向组织的运输和递送 PO2、二氧化碳分压、PH值和氧含量、红细胞2，3-DPG和Hb-O2 解离曲线(P50‘S)；e)呼吸效应的评估 测量VO2、VCO2、VE、VT和呼吸频率； 通过测量心输出量来评估心血管效应， 心率、主动脉和肺动脉压以及心脏重量；g) 豚鼠作为慢性阻塞性肺疾病动物模型的适用性评价 高山病(CMS)。 CMS是一种临床症状，其特征是红细胞增多和 偶尔发生的右心衰竭，发生在一些天生的 高海拔地区“失去”适应能力的人。豚鼠可能是一种很好的 用于研究CMS的动物模型，因为它们在发生临床情况时 暴露在与在人类身上观察到的类似的高海拔条件下。 该模型也可能适用于对发病机制的理解。 以右肺增大为特征的肺心病 脑室，继发于长期的肺部疾病，通常发生在 慢性缺氧和红细胞增多症。此外，这项研究可能会提供 治疗这些疾病的新途径。

Hematological, cardio-pulmonary, and biochemical effects of acute (7 days) and chronic (14 weeks) exposure to hypoxia (T=22 C, P02=80 Torr), cold (Ta=5 C, P02=133 Torr), and cold + hypoxia (Ta =5 Ca, P02=80 Torr) will be investigated in guinea pigs (Cavia porcellus). A control group of animals will be studied under the ambient conditions of our laboratory in Denver (Ta=22 C, PO2=133 Torr). The proposed study is designed to duplicate the recently reported observation that cold blunts the hematological response to hypoxia, and to understand the mechanisms involved in controlling and modulating the hematological response to these environmental stresses. The specific aims include: a) determination of the time course and magnitude of changes in circulating erythropoietin (Ep) with an in vitro Ep bioassay; b) evaluation of the erythropoietic response by measurement of Hct and [Hb], and determination of red cell mass and plasma volume, by examination of tissue cultures, and by counting blood cell types in tissues and whole blood; c) evaluates of other factors, namely catecholamines, growth and thyroid hormones, testosterone, iron uptake and storage sites, and red cell survival, which may influence the level of erythrocytosis; d) evaluation of 02 transport and delivery to tissues by measurement of arterial and venous PO2, PCO2, PH, and oxygen contents, red cell 2,3-DPG, and Hb-O2 dissociation curves (P50's); e) assessment of respiratory effects by measurement of VO2, VCO2, VE, VT, and frequency of respiration; f) assessment of cardio-vascular effects by measurement of cardiac output, heart rate, aortic and pulmonary blood pressures, and heart weights; g) assessment of suitability of the guinea pig as an animal model for Chronic Mountain Sickness (CMS). CMS is a clinical condition characterized by exaggerated erythrocytosis and occasional right heart failure which occurs in some individuals native to high altitude who "lose" their adaptation. Guinea pigs may be a good animal model for the study of CMS as they develop a clinical condition when exposed to high altitude conditions similar to that observed in humans. This model may also be applicable to the understanding of the pathogenesis of cor pulmonale which is characterized by enlargement of the right ventricle, secondary to long standing lung disease, usually occurring with chronic hypoxia and erythrocytosis. In addition, this research may provide new avenues for the treatment of these conditions.