单次吸入与联合吸入β2受体激动剂沙丁胺醇和福莫特罗对计时赛成绩、肺功能、代谢及内分泌变量的急性影响。

Acute Effects of Single Versus Combined Inhaled β2-Agonists Salbutamol and Formoterol on Time Trial Performance, Lung Function, Metabolic and Endocrine Variables.

作者信息

Bizjak Daniel A, Nussbaumer Dorle, Winkert Kay, Treff Gunnar, Takabajashi Kensuke, Mentz Lennart, Schober Franziska, Buhl Jasmine-Lèonike, John Lucas, Dreyhaupt Jens, Steeb Luise, Harps Lukas C, Parr Maria K, Diel Patrick, Zügel Martina, Steinacker Jürgen M

机构信息

Department of Internal Medicine, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, 89075, Ulm, Germany.

Institute of Sports Medicine, Paracelsus Medical University Salzburg, 5020, Salzburg, Austria.

出版信息

Sports Med Open. 2023 Aug 28;9(1):79. doi: 10.1186/s40798-023-00630-3.

DOI:10.1186/s40798-023-00630-3

PMID:37640958

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10462601/

Abstract

BACKGROUND

High prevalence rates of β2-agonist use among athletes in competitive sports makes it tempting to speculate that illegitimate use of β2-agonists boosts performance. However, data regarding the potential performance-enhancing effects of inhaled β2-agonists and its underlying molecular basis are scarce.

METHODS

In total, 24 competitive endurance athletes (12f/12m) participated in a clinical double-blinded balanced four-way block cross-over trial to investigate single versus combined effects of β2-agonists salbutamol (SAL) and formoterol (FOR), to evaluate the potential performance enhancement of SAL (1200 µg, Cyclocaps, Pb Pharma GmbH), FOR (36 µg, Sandoz, HEXAL AG) and SAL + FOR (1200 µg + 36 µg) compared to placebo (PLA, Gelatine capsules containing lactose monohydrate, Pharmacy of the University Hospital Ulm). Measurements included skeletal muscle gene and protein expression, endocrine regulation, urinary/serum β2-agonist concentrations, cardiac markers, cardiopulmonary and lung function testing and the 10-min time trial (TT) performance on a bicycle ergometer as outcome variables. Blood and urine samples were collected pre-, post-, 3 h post- and 24 h post-TT.

RESULTS

Mean power output during TT was not different between study arms. Treatment effects regarding lung function (p < 0.001), echocardiographic (left ventricular end-systolic volume p = 0.037; endocardial global longitudinal strain p < 0.001) and metabolic variables (e.g. NR4A2 and ATF3 pathway) were observed without any influence on performance. In female athletes, total serum β2-agonist concentrations for SAL and FOR were higher. Microarray muscle gene analysis showed a treatment effect for target genes in energy metabolism with strongest effect by SAL + FOR (NR4A2; p = 0.001). Of endocrine variables, follicle-stimulating hormone (3 h Post-Post-TT), luteinizing hormone (3 h Post-Pre-TT) and insulin (Post-Pre-TT) concentrations showed a treatment effect (all p < 0.05).

CONCLUSIONS

No endurance performance-enhancing effect for SAL, FOR or SAL + FOR within the permitted dosages compared to PLA was found despite an acute effect on lung and cardiac function as well as endocrine and metabolic variables in healthy participants. The impact of combined β2-agonists on performance and sex-specific thresholds on the molecular and cardiac level and their potential long-term performance enhancing or health effects have still to be determined.

TRIAL REGISTRATION

Registered at Eudra CT with the number: 2015-005598-19 (09.12.2015) and DRKS with number DRKS00010574 (16.11.2021, retrospectively registered).

摘要

背景

竞技体育运动员中β2激动剂的高使用率使人不禁推测，非法使用β2激动剂可提高成绩。然而，关于吸入性β2激动剂潜在的提高成绩效果及其潜在分子基础的数据却很匮乏。

方法

共有24名竞技耐力运动员（12名女性/12名男性）参与了一项临床双盲平衡四向区组交叉试验，以研究β2激动剂沙丁胺醇（SAL）和福莫特罗（FOR）的单一及联合作用，评估SAL（1200μg，Cyclocaps，Pb Pharma GmbH）、FOR（36μg，Sandoz，HEXAL AG）和SAL+FOR（1200μg+36μg）与安慰剂（PLA，含一水乳糖的明胶胶囊，乌尔姆大学医院药房）相比的潜在成绩提高作用。测量指标包括骨骼肌基因和蛋白表达、内分泌调节、尿/血清β2激动剂浓度、心脏标志物、心肺和肺功能测试以及自行车测力计上的10分钟计时赛（TT）成绩作为结果变量。在TT前、TT后、TT后3小时和TT后24小时采集血液和尿液样本。

结果

各研究组之间TT期间的平均功率输出无差异。观察到肺功能（p<0.001）、超声心动图（左心室收缩末期容积p=0.037；心内膜整体纵向应变p<0.001）和代谢变量（如NR4A2和ATF3途径）的治疗效果，但对成绩无任何影响。在女性运动员中，SAL和FOR的总血清β2激动剂浓度较高。微阵列肌肉基因分析显示能量代谢中靶基因有治疗效果，SAL+FOR的效果最强（NR4A2；p=0.001）。在内分泌变量中，促卵泡激素（TT后3小时）、促黄体生成素（TT前3小时）和胰岛素（TT前-后）浓度显示出治疗效果（均p<0.05）。