ANAEROBIC THRESHOLD DURING EXERCISE

运动期间的无氧阈值

• 批准号: 3083021
• 负责人: DAVID M SYSTROM
• 金额: $ 7.74万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-12-31 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3083021
• 关键词: acidity /alkalinity; ammonia; bioenergetics; blood chemistry; blood pressure; chemoreceptors; citrulline; dichloroacetate; diet; enzyme activity; enzyme deficiency; exercise; glutamates; glycogen storage disease type V; glycolysis; heart rate; human subject; hyperoxia; hypoxia; laboratory rat; lactates; muscle metabolism; nuclear magnetic resonance spectroscopy; nutrition related tag; oxidation; phosphorus; pyruvate dehydrogenase; radionuclides; respiratory gas analyzer; respiratory gas transport

During heavy exercise, blood lactate rises vs. resting values (Lactate Threshold, LT) and ventilation increases out of proportion to the metabolic rate (Ventilatory Threshold, VT). The two phenomena have been linked mechanistically under the umbrella term, "Anaerobic Threshold" (AT). Exercise above the AT is manifested by fatigue and dyspnea which occur with minimal effort in patients with heart and lung disease. The AT hypothesis states that the LT and VT are related to insufficient supply of oxygen to working muscle and increased ventilatory drive due to lactic acid, respectively. Recent data from this and other laboratories have suggested other explanations. The long-term goal of this project, therefore, is to better understand the biochemical and physiologic events during exercise responsible for the LT and VT in hopes of improving patients'exercise tolerance. This laboratory has recently utilized state of the art breath-by-breath gas exchange measurements and continuous 31P Magnetic Resonance Spectroscopy (MRS) in an attempt to link intracellular muscle metabolism with changes in blood lactate and ventilation during incremental exercise. Our published and pilot data suggest that the LT may be more related to increases in ammonia than to mitochondrial hypoxia (Systrom, Circ) and that the VT may correlate better with a rise in intramuscular hydrogen ion or blood ammonia than with a rise in blood lactate (Systrom, JAP). In the proposed human studies that follow, the purported role of tissue hypoxia in causing the LT will be examined by measuring intracellular pH with 31P MRS, blood lactate and ammonia during hypoxic exercise and after facilitation of lactate oxidation by dichloroacetate. To readdress the concept of a causal link between blood lactate and ventilation during exercise, both will be measured after manipulation of intramuscular pH by an hypoxic inspired fraction of oxygen, after dichloroacetate and training. Ammonia's role in the genesis of the LT and VT will be elucidated by increasing ammonia clearance via monosodium glutamate and citrulline in normals, glycogen depleted subjects and in patients with McArdle's disease and by examining the LT and VT in patients whose exercising muscle is incapable of NH3 production (myoadenylate deaminase deficiency). Preliminary work from this laboratory, if confirmed by the proposed studies, will offer alternative explanations for the "Anaerobic Threshold" and suggest new diagnostic and therapeutic modalities for cardiopulmonary patients. The Principal Investigator's interest in control of ventilation during exercise stems from earlier work in the Sponsor's laboratory which defined a role for central amino acid neurotransmitters in the regulation of resting ventilation. Over the past 3 years, he has used 31P MRS to continuously and noninvasively compare intramuscular metabolic events to changes in blood metabolites and ventilation during exercise. The Harvard Medical School environment is uniquely equipped to pursue the specific aims of this proposal. To our knowledge, no other facility has sufficient resources to simultaneously measure large muscle 31P MRS, blood chemistry, breath-by-breath ventilation and gas exchange.

在剧烈运动期间，血液乳酸盐相对于静息值（乳酸盐 阈值（LT）和通气量的增加与代谢不成比例 通气阈值（Ventilatory Threshold，VT）。 这两种现象被联系在一起 无氧阈（Anaerobic Threshold，AT）。 AT以上的运动表现为疲劳和呼吸困难， 心脏和肺部疾病患者的最小努力。 AT假说 指出LT和VT与氧气供应不足有关， 工作肌肉和增加的乳酸驱动力， 分别 这个实验室和其他实验室的最新数据表明， 其他解释。 因此，该项目的长期目标是 更好地了解运动过程中的生化和生理事件 负责LT和VT，希望改善患者的运动 宽容 这个实验室最近使用了最先进的 逐呼吸气体交换测量和连续31P磁 共振光谱（MRS），试图将细胞内肌肉 代谢与血乳酸和通气量的变化， 锻炼的 我们公布的数据和试点数据表明，LT可能更多 与氨的增加相关而不是与线粒体缺氧相关（Systrom， Circ），VT可能与肌内 氢离子或血氨比随着血乳酸盐的升高（Systrom， JAP）。 在接下来的人类研究中， 组织缺氧引起LT将通过测量 缺氧时细胞内pH值、血乳酸和血氨变化 运动和二氯乙酸促进乳酸氧化后。 重新探讨血乳酸与 运动期间的通气量，两者都将在操作后进行测量。 肌内pH值的低氧吸入分数的氧气，后 二氯乙酸和训练。 氨在LT发生中的作用， VT将通过增加氨清除率来阐明， 正常人、糖原耗竭受试者和 McArdle病患者的LT和VT检查 其运动肌肉不能产生NH3（肌腺苷酸 脱氨酶缺乏）。 实验室的初步工作，如果证实 通过拟议的研究，将提供替代解释， “无氧阈值”，并提出新的诊断和治疗方式 对于心肺病人。 主要研究者的兴趣 运动期间的通风控制源于早期的工作， 确定中心氨基酸作用的申办方实验室 神经递质调节静息通气。 过去 3年来，他一直使用31P MRS连续和无创地比较 肌内代谢事件与血液代谢物变化之间的关系， 运动时通风。 哈佛医学院的环境是 有能力实现这一建议的具体目标。 对我们 知识，没有其他设施有足够的资源，同时 测量大肌肉31P MRS、血液化学、逐呼吸通气 气体交换。