AMMONIA, FATIGUE AND VENTILATION DURING EXERCISE

在考虑减少(糖原)的大强度运动时 消耗或消除(麦卡德尔综合征，MCAS)骨骼肌 产生乳酸，注意疲劳和呼吸控制 完好无损。GD和MCAS的特点是NH3在 肌肉和血液。NH3抑制氧化代谢，是一种已知的 呼吸性昏迷药在肝病患者休息期的应用。它是 因此，NH3可能导致疲劳和呼吸困难。 运动时应注意不发生极地酸血症。另一种可能性是， 运动骨骼肌代谢产物直接刺激换气 通过神经通路。这种所谓的“新陈代谢反射”可以被研究 通过非侵入性31P磁共振波谱测量 双侧静脉闭塞(BVO)时的骨骼肌锻炼 血压手铐。 一种孤儿药物(苯丁酸钠，NaPB)最近被 FDA用于预防和治疗与以下疾病相关的高氨血症 儿童和成人的尿素循环障碍。峰值血浆水平是 口服5g后1h达峰。NaPB通过β氧化转化 线粒体中的苯乙酸钠盐(Napa)。纳帕与 肝脏和肾脏中的谷氨酰胺形成苯乙酰谷氨酰胺， 与它的两个废氮一起，在随后的尿液中排出 24小时。100多年的用药经验表明， 严重的毒性。因此，我们希望使用单剂量的NaPB 抑制肌肉和血液中的NH3，并确定其在疲劳和 运动时的通风。

During heavy exercise under considerations which decrease (glycogen depletion, GD) or eliminate (McArdle's Syndrome, McAS) skeletal muscle lactic acid production, fatigue is noted and ventilatory control is intact. GD and McAS are characterized by an exorbitant NH3 rise in muscle and blood. NH3 inhibits oxidative metabolism3 and is a known respiratory analeptic in resting patients with liver disease. It is therefore possible that NH3 contributes to fatigue and dyspenea during exercise when lctic acidemia does not. Another possibility is that exercising skeletal muscle metabolites stimulate ventilation directly through a neural pathway. This so-called "metaboreflex" can be examined by non-invasive 31P magnetic resonance spectroscopy measurements of exercising skeletal muscle during bilateral venous occlusion (BVO) by blood pressure cuffs. An orphan drug (sodium phenylbutyrate, NaPB) was recently approved by the FDA for prevention and treatment of hyperammonemia associated with urea cycle disorders of children and adults. Peak plasma levels are acheived 1 h after 5 g po by mouth. NaPB is converted by betaoxidation in the mitochondrion to Na Phenylacetate (NaPA). NaPA congugates with glutamine in the liver and kidney to form phenylacetylglutamine which, with its 2 waste nitrogens, is excreted in the urine over the ensuing 24 h. Over 100 patient-years experience with the drug have revealed no serious toxicity. We therefore wish to use a single oral dose of NaPB to suppress muscle and blood NH3 and determine its role in fatigue and ventilation during exercise.