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EFFECTS OF COLD ON ACCLIMATION TO HYPOXIA

寒冷对缺氧适应的影响

基本信息

批准号：
3343466
负责人：
NATALIO BANCHERO
金额：
$ 11.85万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-05-01 至 1988-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3343466
关键词：
acclimatization altitude blood cell count blood volume cardiopulmonary disease cardiovascular function catecholamines disease /disorder model environmental stressor erythropoietin iron metabolism oxygen transport respiratory function respiratory hypoxia stress testosterone thyroid hormones tissue /cell culture

项目摘要

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.

急性（7 天）的血液学、心肺和生化影响和长期（14 周）暴露于缺氧（T=22 C，P02=80 Torr）、寒冷（Ta=5℃，P02=133Torr），冷+缺氧（Ta=5Ca，P02=80Torr）在豚鼠（Cavia porcellus）中进行了研究。对照组动物将在我们丹佛实验室的环境条件下进行研究（Ta=22℃，PO2=133托）。拟议的研究旨在重复最近报道的观察表明寒冷会减弱血液反应缺氧，并了解控制和控制所涉及的机制调节对这些环境应激的血液学反应。这具体目标包括： a) 确定时间进程和幅度通过体外 Ep 生物测定观察循环促红细胞生成素 (Ep) 的变化； b) 通过测量 Hct 来评估红细胞生成反应 [Hb]，并通过检查测定红细胞质量和血浆容量组织培养物，并通过计数组织和整体中的血细胞类型血; c) 评估其他因素，即儿茶酚胺、生长和甲状腺激素、睾酮、铁的吸收和储存部位以及红细胞生存，这可能会影响红细胞增多的水平； d) 评估 02 通过测量动脉和静脉来运输和递送至组织 PO2、PCO2、PH 和氧含量、红细胞 2,3-DPG 和 Hb-O2 解离曲线（P50）； e) 评估呼吸系统影响测量 VO2、VCO2、VE、VT 和呼吸频率； f）通过测量心输出量评估心血管效应，心率、主动脉血压和肺动脉血压以及心脏重量；克）豚鼠作为慢性病动物模型的适宜性评估高山病（CMS）。 CMS 是一种临床病症，其特征是红细胞增多和偶尔发生右心衰竭，发生在某些原住民身上高海拔者“失去”适应能力。豚鼠可能是个好东西用于研究 CMS 的动物模型，因为它们在以下情况下会出现临床症状：暴露于与人类观察到的类似的高海拔条件。该模型也可能适用于发病机制的理解肺心病，其特征是右肺增大心室，继发于长期肺部疾病，通常发生于慢性缺氧和红细胞增多。此外，这项研究可能会提供治疗这些疾病的新途径。