Advertisement

European Journal of Applied Physiology

, Volume 114, Issue 12, pp 2499–2508 | Cite as

High-dose inhaled terbutaline increases muscle strength and enhances maximal sprint performance in trained men

  • Morten HostrupEmail author
  • Anders Kalsen
  • Jens Bangsbo
  • Peter Hemmersbach
  • Sebastian Karlsson
  • Vibeke Backer
Original Article

Abstract

Purpose

The purpose of the present study was to investigate the effect of high-dose inhaled terbutaline on muscle strength, maximal sprinting, and time-trial performance in trained men.

Methods

Nine non-asthmatic males with a \(\dot{V}O_{2max}\) of 58.9 ± 3.1 ml min−1 kg−1 (mean ± SEM) participated in a double-blinded randomized crossover study. After administration of inhaled terbutaline (30 × 0.5 mg) or placebo, subjects’ maximal voluntary isometric contraction (MVC) of m.quadriceps was measured. After MVC, subjects performed a 30-s Wingate test. Sixty minutes following the Wingate test, subjects exercised for 10 min at 80 % of \(\dot{V}O_{2max}\) and completed a 100-kcal time trial. Aerobic contribution was determined during the Wingate test by indirect calorimetry. Furthermore, plasma terbutaline, lactate, glucose, and K+ were measured.

Results

Inhalation of 15 mg terbutaline resulted in systemic concentrations of terbutaline of 23.6 ± 1.1 ng ml−1 30 min after administration, and elevated plasma lactate (P = 0.001) and glucose (P = 0.007). MVC was higher for terbutaline than placebo (738 ± 64 vs. 681 ± 68 N) (P = 0.007). In addition, Wingate peak power and mean power were 2.2 ± 0.8 (P = 0.019) and 3.3 ± 1.0 % (P = 0.009) higher for terbutaline than placebo. Net accumulation of plasma lactate was higher (P = 0.003) for terbutaline than placebo during the Wingate test, whereas \(\dot{V}O_{2}\) above baseline was unchanged by terbutaline (P = 0.882). Time-trial performance was not different between treatments (P = 0.236).

Conclusion

High-dose inhaled terbutaline elicits a systemic response that enhances muscle strength and sprint performance. High-dose terbutaline should therefore continue to be restricted in competitive sport.

Keywords

Beta2-agonist Doping Athletes Force Pharmacology 

Abbreviations

ANOVA

Analysis of the variance

AUC

Area under the curve

MVC

Maximal voluntary Contraction

RER

Respiratory exchange ratio

\(\dot{V}O_{2}\)

Oxygen uptake

\(\dot{V}O_{2max}\)

Maximal oxygen uptake

WADA

World Anti-doping Agency

Notes

Acknowledgments

The study was supported by a grant from the World Anti-doping Agency (WADA).

Conflict of interest

None.

References

  1. Andersson DC, Betzenhauser MJ, Reiken S, Umanskaya A, Shiomi T, Marks AR (2012) Stress-induced increase in skeletal muscle force requires protein kinase A phosphorylation of the ryanodine receptor. J Physiol 590(Pt 24):6381–6387. doi: 10.1113/jphysiol.2012.237925 PubMedCentralPubMedCrossRefGoogle Scholar
  2. Arlettaz A, Le Panse B, Portier H, Lecoq AM, Thomasson R, De Ceaurriz J, Collomp K (2009) Salbutamol intake and substrate oxidation during submaximal exercise. Eur J Appl Physiol 105(2):207–213. doi: 10.1007/s00421-008-0891-7 PubMedCrossRefGoogle Scholar
  3. Backer V, Lund T, Pedersen L (2007) Pharmaceutical treatment of asthma symptoms in elite athletes-doping or therapy? Scand J Med Sci Sports 17(6):615–622. doi: 10.1111/j.1600-0838.2007.00711.x PubMedCrossRefGoogle Scholar
  4. Bengtsson B, Fagerstrom PO (1982) Extrapulmonary effects of terbutaline during prolonged administration. Clin Pharmacol Ther 31(6):726–732PubMedCrossRefGoogle Scholar
  5. Butler J, O’Brien M, O’Malley K, Kelly JG (1982) Relationship of beta-adrenoreceptor density to fitness in athletes. Nature 298(5869):60–62PubMedCrossRefGoogle Scholar
  6. Cairns SP, Dulhunty AF (1993a) Beta-adrenergic potentiation of E-C coupling increases force in rat skeletal muscle. Muscle Nerve 16(12):1317–1325. doi: 10.1002/mus.880161208 PubMedCrossRefGoogle Scholar
  7. Cairns SP, Dulhunty AF (1993b) The effects of beta-adrenoceptor activation on contraction in isolated fast- and slow-twitch skeletal muscle fibres of the rat. Br J Pharmacol 110(3):1133–1141PubMedCentralPubMedCrossRefGoogle Scholar
  8. Cairns SP, Dulhunty AF (1994) Beta-adrenoceptor activation shows high-frequency fatigue in skeletal muscle fibers of the rat. Am J Physiol 266(5 Pt 1):C1204–C1209PubMedGoogle Scholar
  9. Carlsen KH, Ingjer F, Kirkegaard H, Thyness B (1997) The effect of inhaled salbutamol and salmeterol on lung function and endurance performance in healthy well-trained athletes. Scand J Med Sci Sports 7(3):160–165PubMedCrossRefGoogle Scholar
  10. Clausen T, Flatman JA (1980) Beta 2-adrenoceptors mediate the stimulating effect of adrenaline on active electrogenic Na-K-transport in rat soleus muscle. Br J Pharmacol 68(4):749–755PubMedCentralPubMedCrossRefGoogle Scholar
  11. Collomp K, Candau R, Collomp R, Carra J, Lasne F, Prefaut C, De Ceaurriz J (2000) Effects of acute ingestion of salbutamol during submaximal exercise. Int J Sports Med 21(7):480–484. doi: 10.1055/s-2000-7422 PubMedCrossRefGoogle Scholar
  12. Collomp K, Le Panse B, Portier H, Lecoq AM, Jaffre C, Beaupied H, Richard O, Benhamou L, Courteix D, De Ceaurriz J (2005) Effects of acute salbutamol intake during a Wingate test. Int J Sports Med 26(7):513–517. doi: 10.1055/s-2004-821223 PubMedCrossRefGoogle Scholar
  13. Crivelli G, Millet GP, Gremion G, Borrani F (2011) Effects of salbutamol on the contractile properties of human skeletal muscle before and after fatigue. Acta Physiol (Oxf) 203(2):311–320. doi: 10.1111/j.1748-1716.2011.02302.x CrossRefGoogle Scholar
  14. Crivelli G, Borrani F, Capt R, Gremion G, Maffiuletti NA (2013) Actions of beta2-Adrenoceptor Agonist Drug on Human Soleus Muscle Contraction. Med Sci Sports Exerc. doi: 10.1249/MSS.0b013e318284706a PubMedGoogle Scholar
  15. Decorte N, Verges S, Flore P, Guinot M, Wuyam B (2008) Effects of acute salbutamol inhalation on quadriceps force and fatigability. Med Sci Sports Exerc 40(7):1220–1227. doi: 10.1249/MSS.0b013e31816b87aa PubMedCrossRefGoogle Scholar
  16. Decorte N, Bachasson D, Guinot M, Flore P, Levy P, Verges S, Wuyam B (2013) Impact of Salbutamol on Neuromuscular Function in Endurance Athletes. Med Sci Sports Exerc. doi: 10.1249/MSS.0b013e3182951d2d PubMedGoogle Scholar
  17. Elers J, Hostrup M, Pedersen L, Henninge J, Hemmersbach P, Dalhoff K, Backer V (2012a) Urine and serum concentrations of inhaled and oral terbutaline. Int J Sports Med 33(12):1026–1033. doi: 10.1055/s-0032-1311590 PubMedCrossRefGoogle Scholar
  18. Elers J, Morkeberg J, Jansen T, Belhage B, Backer V (2012b) High-dose inhaled salbutamol has no acute effects on aerobic capacity or oxygen uptake kinetics in healthy trained men. Scand J Med Sci Sports 22(2):232–239. doi: 10.1111/j.1600-0838.2010.01251.x PubMedCrossRefGoogle Scholar
  19. Elers J, Pedersen L, Henninge J, Hemmersbach P, Dalhoff K, Backer V (2012c) The pharmacokinetic profile of inhaled and oral salbutamol in elite athletes with asthma and nonasthmatic subjects. Clin J Sport Med Off J Can Acad Sport Med 22(2):140–145. doi: 10.1097/JSM.0b013e31823513e1 CrossRefGoogle Scholar
  20. Gomes Alves G, Sola-Penna M (2003) Epinephrine modulates cellular distribution of muscle phosphofructokinase. Mol Genet Metab 78(4):302–306PubMedCrossRefGoogle Scholar
  21. Goubault C, Perault MC, Leleu E, Bouquet S, Legros P, Vandel B, Denjean A (2001) Effects of inhaled salbutamol in exercising non-asthmatic athletes. Thorax 56(9):675–679PubMedCentralPubMedCrossRefGoogle Scholar
  22. Heir T, Stemshaug H (1995) Salbutamol and high-intensity treadmill running in nonasthmatic highly conditioned athletes. Scand J Med Sci Sports 5(4):231–236PubMedCrossRefGoogle Scholar
  23. Helenius IJ, Tikkanen HO, Sarna S, Haahtela T (1998) Asthma and increased bronchial responsiveness in elite athletes: atopy and sport event as risk factors. J Allergy Clin Immunol 101(5):646–652. doi: 10.1016/S0091-6749(98)70173-3 PubMedCrossRefGoogle Scholar
  24. Juel C (1988) The effect of beta 2-adrenoceptor activation on ion-shifts and fatigue in mouse soleus muscles stimulated in vitro. Acta Physiol Scand 134(2):209–216. doi: 10.1111/j.1748-1716.1988.tb08481.x PubMedCrossRefGoogle Scholar
  25. Kalsen A, Hostrup M, Bangsbo J, Backer V (2013) Combined inhalation of beta-agonists improves swim ergometer sprint performance but not high-intensity swim performance. Scand J Med Sci Sports. doi: 10.1111/sms.12096 PubMedGoogle Scholar
  26. Kindermann W (2007) Do inhaled beta(2)-agonists have an ergogenic potential in non-asthmatic competitive athletes? Sports Med 37(2):95–102PubMedCrossRefGoogle Scholar
  27. Kjaer M, Howlett K, Langfort J, Zimmerman-Belsing T, Lorentsen J, Bulow J, Ihlemann J, Feldt-Rasmussen U, Galbo H (2000) Adrenaline and glycogenolysis in skeletal muscle during exercise: a study in adrenalectomised humans. J Physiol 528(Pt 2):371–378PubMedCentralPubMedCrossRefGoogle Scholar
  28. Langdeau JB, Turcotte H, Bowie DM, Jobin J, Desgagne P, Boulet LP (2000) Airway hyperresponsiveness in elite athletes. Am J Respir Crit Care Med 161(5):1479–1484. doi: 10.1164/ajrccm.161.5.9909008 PubMedCrossRefGoogle Scholar
  29. Le Panse B, Arlettaz A, Portier H, Lecoq AM, De Ceaurriz J, Collomp K (2007) Effects of acute salbutamol intake during supramaximal exercise in women. Br J Sports Med 41(7):430–434. doi: 10.1136/bjsm.2006.033845 PubMedCentralPubMedCrossRefGoogle Scholar
  30. McKenzie DC, Fitch KD (2011) The asthmatic athlete: inhaled Beta-2 agonists, sport performance, and doping. Clin J Sport Med Off J Can Acad Sport Med 21(1):46–50. doi: 10.1097/IAE.0b013e318203c0ef CrossRefGoogle Scholar
  31. McKenzie DC, Rhodes EC, Stirling DR, Wiley JP, Dunwoody DW, Filsinger IB, Jang F, Stevens A (1983) Salbutamol and treadmill performance in non-atopic athletes. Med Sci Sports Exerc 15(6):520–522PubMedCrossRefGoogle Scholar
  32. Norris SR, Petersen SR, Jones RL (1996) The effect of salbutamol on performance in endurance cyclists. Eur J Appl Physiol 73(3–4):364–368CrossRefGoogle Scholar
  33. Pluim BM, de Hon O, Staal JB, Limpens J, Kuipers H, Overbeek SE, Zwinderman AH, Scholten RJ (2011) Beta (2)-Agonists and physical performance: a systematic review and meta-analysis of randomized controlled trials. Sports Med 41(1):39–57. doi: 10.2165/11537540-000000000-00000 PubMedCrossRefGoogle Scholar
  34. Rudolf R, Magalhaes PJ, Pozzan T (2006) Direct in vivo monitoring of sarcoplasmic reticulum Ca2+ and cytosolic cAMP dynamics in mouse skeletal muscle. J Cell Biol 173(2):187–193. doi: 10.1083/jcb.200601160 PubMedCentralPubMedCrossRefGoogle Scholar
  35. Sanchez AM, Collomp K, Carra J, Borrani F, Coste O, Prefaut C, Candau R (2012) Effect of acute and short-term oral salbutamol treatments on maximal power output in non-asthmatic athletes. Eur J Appl Physiol 112(9):3251–3258. doi: 10.1007/s00421-011-2307-3 PubMedCrossRefGoogle Scholar
  36. Sanchez AM, Borrani F, Le Fur MA, Le Mieux A, Lecoultre V, Py G, Gernigon C, Collomp K, Candau R (2013) Acute supra-therapeutic oral terbutaline administration has no ergogenic effect in non-asthmatic athletes. Eur J Appl Physiol 113(2):411–418. doi: 10.1007/s00421-012-2447-0 PubMedCrossRefGoogle Scholar
  37. Sandsund M, Sue-Chu M, Helgerud J, Reinertsen RE, Bjermer L (1998) Effect of cold exposure (−15 degrees C) and salbutamol treatment on physical performance in elite nonasthmatic cross-country skiers. Eur J Appl Physiol 77(4):297–304CrossRefGoogle Scholar
  38. Schmekel B, Borgstrom L, Wollmer P (1992) Exercise increases the rate of pulmonary absorption of inhaled terbutaline. Chest 101(3):742–745PubMedCrossRefGoogle Scholar
  39. Seebacher F, Pollard SR, James RS (2012) How well do muscle biomechanics predict whole-animal locomotor performance? The role of Ca2 + handling. J Exp Biol 215(Pt 11):1847–1853. doi: 10.1242/jeb.067918 PubMedCrossRefGoogle Scholar
  40. Signorile JF, Kaplan TA, Applegate B, Perry AC (1992) Effects of acute inhalation of the bronchodilator, albuterol, on power output. Med Sci Sports Exerc 24(6):638–642PubMedCrossRefGoogle Scholar
  41. Slack JP, Grupp IL, Luo W, Kranias EG (1997) Phospholamban ablation enhances relaxation in the murine soleus. Am J Physiol 273(1 Pt 1):C1–C6PubMedGoogle Scholar
  42. Sporer BC, Sheel AW, McKenzie DC (2008) Dose response of inhaled salbutamol on exercise performance and urine concentrations. Med Sci Sports Exerc 40(1):149–157. doi: 10.1249/mss.0b013e3181591df7 PubMedCrossRefGoogle Scholar
  43. van Baak MA, Mayer LH, Kempinski RE, Hartgens F (2000) Effect of salbutamol on muscle strength and endurance performance in nonasthmatic men. Med Sci Sports Exerc 32(7):1300–1306PubMedCrossRefGoogle Scholar
  44. van Baak MA, de Hon OM, Hartgens F, Kuipers H (2004) Inhaled salbutamol and endurance cycling performance in non-asthmatic athletes. Int J Sports Med 25(7):533–538. doi: 10.1055/s-2004-815716 PubMedCrossRefGoogle Scholar
  45. Watt MJ, Howlett KF, Febbraio MA, Spriet LL, Hargreaves M (2001) Adrenaline increases skeletal muscle glycogenolysis, pyruvate dehydrogenase activation and carbohydrate oxidation during moderate exercise in humans. J Physiol 534(Pt 1):269–278PubMedCentralPubMedCrossRefGoogle Scholar
  46. Wolfarth B, Wuestenfeld JC, Kindermann W (2010) Ergogenic effects of inhaled beta2-agonists in non-asthmatic athletes. Endocrinol Metab Clin North Am 39 (1):75–87, ix. doi: 10.1016/j.ecl.2009.10.005

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Morten Hostrup
    • 1
    • 2
    Email author
  • Anders Kalsen
    • 1
    • 2
  • Jens Bangsbo
    • 1
  • Peter Hemmersbach
    • 3
  • Sebastian Karlsson
    • 2
  • Vibeke Backer
    • 2
  1. 1.Department of Nutrition, Exercise and Sports, Section of Integrated PhysiologyUniversity of CopenhagenCopenhagenDenmark
  2. 2.Respiratory Research UnitBispebjerg University HospitalCopenhagenDenmark
  3. 3.Norwegian Doping Control LaboratoryOslo University HospitalOsloNorway

Personalised recommendations