ANAEROBIC THRESHOLD DURING EXERCISE

运动期间的无氧阈值

• 批准号: 3083022
• 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/3083022
• 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.

在剧烈运动中，血乳酸相对于静止值(乳酸)升高 阈值和通气量的增加与新陈代谢不成比例 心率(呼吸阈值，VT)。这两种现象是有联系的。 机械术语为“无氧阈值”(AT)。 AT以上的运动表现为疲劳和呼吸困难，发生在 心肺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 工作肌肉和由于乳酸而增加的通风驱动力， 分别进行了分析。来自该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 更好地了解运动中的生化和生理事件 负责LT和VT，希望改善患者的锻炼 宽容。这个实验室最近利用了最先进的技术 逐呼吸气体交换测量和连续31P磁化 磁共振波谱(MRS)在连接细胞内肌肉中的尝试 递增负荷时血乳酸和通气量的变化与代谢 锻炼身体。我们公布的和试点数据表明，LT可能会更高 与氨的增加有关，而不是与线粒体缺氧有关(Systrom， 中国保监会)，室速可能与肌肉内的上升更好地相关 氢离子或血氨比血乳酸升高(Systrom， JAP)。在随后提出的人体研究中，所谓的作用是 将通过测量来检查引起LT的组织缺氧 低氧时31P MRS检测细胞内pH、血乳酸和氨 运动和二氯乙酸酯促进乳酸氧化后。 重新解释血乳酸和血乳酸之间存在因果关系的概念 运动时的通气量，两者都将在操控后进行测量 肌肉内pH由低氧刺激的部分氧气引起，在 二氯乙酸酯和训练。氨在低温层和低温层形成中的作用 VT将通过增加单钠对氨的清除来阐明。 谷氨酸和瓜氨酸在正常人、糖原耗竭者和 McArdle病患者的LT和VT的检测 谁的运动肌肉不能产生NH3(肌腺苷 脱氨酶缺乏症)。该实验室的初步工作，如果得到确认 通过拟议的研究，将为 “无氧阈值”，并提出新的诊断和治疗模式 适用于心肺疾病患者。首席调查员对 运动期间的通风控制源于 赞助商的实验室，确定了中央氨基酸的作用 静息换气调节中的神经递质。在过去的时间里 3年来，他使用了31P MRS连续无创比较 肌肉内代谢事件对血液代谢物和 运动时的通风。哈佛医学院的环境是 具备独特的能力来实现这项提案的具体目标。致我们的 知识，没有其他设施有足够的资源来同时 测量大肌肉31P磁共振波谱、血化学、呼吸通气量 和气体交换。