Skip to main content
SpringerLink
Log in

Sildenafil does not improve steady state cardiovascular hemodynamics, peak power, or 15-km time trial cycling performance at simulated moderate or high altitudes in men and women

  • Original Article
  • Published:
European Journal of Applied Physiology Aims and scope Submit manuscript

Abstract

Sildenafil improves oxygen delivery and maximal exercise capacity at very high altitudes (≥4,350 m), but it is unknown whether sildenafil improves these variables and longer-duration exercise performance at moderate and high altitudes where competitions are more common. The purpose of this study was to determine the effects of sildenafil on cardiovascular hemodynamics, arterial oxygen saturation (SaO2), peak exercise capacity (W peak), and 15-km time trial performance in endurance-trained subjects at simulated moderate (MA; ~2,100 m, 16.2% FIO2) and high (HA; ~3,900 m, 12.8% FIO2) altitudes. Eleven men and ten women completed two HA W peak trials after ingesting placebo or 50 mg sildenafil. Subjects then completed four exercise trials (30 min at 55% of altitude-specific W peak + 15-km time trial) at MA and HA after ingesting placebo or 50 mg sildenafil. All trials were performed in randomized, counterbalanced, and double-blind fashion. Sildenafil had little influence on cardiovascular hemodynamics at MA or HA, but did result in higher SaO2 values (+3%, p < 0.05) compared to placebo during steady state and time trial exercise at HA. W peak at HA was 19% lower than SL (p < 0.001) and was not significantly affected by sildenafil. Similarly, the significantly slower time trial performance at MA (28.1 ± 0.5 min, p = 0.016) and HA (30.3 ± 0.6 min, p < 0.001) compared to SL (27.5 ± 0.6 min) was unaffected by sildenafil. We conclude that sildenafil is unlikely to exert beneficial effects at altitudes <4,000 m for a majority of the population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Bartsch P, Maggiorini M, Mairbaurl H, Vock P, Swenson ER (2002) Pulmonary extravascular fluid accumulation in climbers. Lancet 360:571; author reply 571–572. doi:10.1016/S0140-6736(02)09723-4

  • Boolell M, Allen MJ, Ballard SA et al (1996a) Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 8:47–52

    PubMed  CAS  Google Scholar 

  • Boolell M, Gepi-Attee S, Gingell JC, Allen MJ (1996b) Sildenafil, a novel effective oral therapy for male erectile dysfunction. Br J Urol 78:257–261

    Article  PubMed  CAS  Google Scholar 

  • Boushel R, Calbet JA, Radegran G, Sondergaard H, Wagner PD, Saltin B (2001) Parasympathetic neural activity accounts for the lowering of exercise heart rate at high altitude. Circulation 104:1785–1791

    Article  PubMed  CAS  Google Scholar 

  • Calbet JA, Boushel R, Radegran G, Sondergaard H, Wagner PD, Saltin B (2003a) Determinants of maximal oxygen uptake in severe acute hypoxia. Am J Physiol Regul Integr Comp Physiol 284:R291–R303. doi:10.1152/ajpregu.00155.2002

    PubMed  CAS  Google Scholar 

  • Calbet JA, Boushel R, Radegran G, Sondergaard H, Wagner PD, Saltin B (2003b) Why is VO2 max after altitude acclimatization still reduced despite normalization of arterial O2 content? Am J Physiol Regul Integr Comp Physiol 284:R304–R316. doi:10.1152/ajpregu.00156.2002

    PubMed  CAS  Google Scholar 

  • Carson CC 3rd (2007) Phosphodiesterase type 5 inhibitors: state of the therapeutic class. Urol Clin North Am 34:507–515, vi. doi:10.1016/j.ucl.2007.08.013

    Google Scholar 

  • Charloux A, Lonsdorfer-Wolf E, Richard R et al (2000) A new impedance cardiograph device for the non-invasive evaluation of cardiac output at rest and during exercise: comparison with the “direct” Fick method. Eur J Appl Physiol 82:313–320

    Article  PubMed  CAS  Google Scholar 

  • Cremona G, Asnaghi R, Baderna P et al (2002) Pulmonary extravascular fluid accumulation in recreational climbers: a prospective study. Lancet 359:303–309

    Article  PubMed  Google Scholar 

  • Dehnert C, Risse F, Ley S et al (2006) Magnetic resonance imaging of uneven pulmonary perfusion in hypoxia in humans. Am J Respir Crit Care Med 174:1132–1138. doi:10.1164/rccm.200606-780OC

    Article  PubMed  Google Scholar 

  • Dehnert C, Berger MM, Mairbaurl H, Bartsch P (2007) High altitude pulmonary edema: a pressure-induced leak. Respir Physiol Neurobiol 158:266–273. doi:10.1016/j.resp.2007.05.002

    Article  PubMed  Google Scholar 

  • Faoro V, Lamotte M, Deboeck G et al (2007) Effects of sildenafil on exercise capacity in hypoxic normal subjects. High Alt Med Biol 8:155–163. doi:10.1089/ham.2007.1058

    Article  PubMed  CAS  Google Scholar 

  • Fulco CS, Rock PB, Cymerman A (1998) Maximal and submaximal exercise performance at altitude. Aviat Space Environ Med 69:793–801

    PubMed  CAS  Google Scholar 

  • Ghofrani HA, Wiedemann R, Rose F et al (2002) Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. Lancet 360:895–900. doi:10.1016/S0140-6736(02)11024-5

    Article  PubMed  CAS  Google Scholar 

  • Ghofrani HA, Reichenberger F, Kohstall MG et al (2004) Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: a randomized, double-blind, placebo-controlled crossover trial. Ann Intern Med 141:169–177

    PubMed  CAS  Google Scholar 

  • Guazzi M, Tumminello G, Di Marco F, Fiorentini C, Guazzi MD (2004) The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure. J Am Coll Cardiol 44:2339–2348. doi:10.1016/j.jacc.2004.09.041

    Article  PubMed  CAS  Google Scholar 

  • Hlastala MP, Lamm WJ, Karp A, Polissar NL, Starr IR, Glenny RW (2004) Spatial distribution of hypoxic pulmonary vasoconstriction in the supine pig. J Appl Physiol 96:1589–1599. doi:10.1152/japplphysiol.00211.2003

    Article  PubMed  Google Scholar 

  • Hopkins SR, Bogaard HJ, Niizeki K, Yamaya Y, Ziegler MG, Wagner PD (2003) Beta-adrenergic or parasympathetic inhibition, heart rate and cardiac output during normoxic and acute hypoxic exercise in humans. J Physiol 550:605–616. doi:10.1113/jphysiol.2003.040568

    Article  PubMed  CAS  Google Scholar 

  • Hsu AR, Barnholt KE, Grundmann NK, Lin JH, McCallum SW, Friedlander AL (2006) Sildenafil improves cardiac output and exercise performance during acute hypoxia, but not normoxia. J Appl Physiol 100:2031–2040. doi:10.1152/japplphysiol.00806.2005

    Article  PubMed  CAS  Google Scholar 

  • Hultgren HN, Grover RF (1968) Circulatory adaptation to high altitude. Annu Rev Med 19:119–152. doi:10.1146/annurev.me.19.020168.001003

    Article  PubMed  CAS  Google Scholar 

  • Jeukendrup A, Saris WH, Brouns F, Kester AD (1996) A new validated endurance performance test. Med Sci Sports Exerc 28:266–270

    Article  PubMed  CAS  Google Scholar 

  • Maggiorini M, Melot C, Pierre S et al (2001) High-altitude pulmonary edema is initially caused by an increase in capillary pressure. Circulation 103:2078–2083

    PubMed  CAS  Google Scholar 

  • Nichols DJ, Muirhead GJ, Harness JA (2002) Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionality. Br J Clin Pharmacol 53(Suppl 1):5S–12S

    Article  PubMed  CAS  Google Scholar 

  • Peltonen JE, Tikkanen HO, Rusko HK (2001) Cardiorespiratory responses to exercise in acute hypoxia, hyperoxia and normoxia. Eur J Appl Physiol 85:82–88

    Article  PubMed  CAS  Google Scholar 

  • Richalet JP, Gratadour P, Robach P et al (2005) Sildenafil inhibits altitude-induced hypoxemia and pulmonary hypertension. Am J Respir Crit Care Med 171:275–281. doi:10.1164/rccm.200406-804OC

    Article  PubMed  Google Scholar 

  • Richard R, Lonsdorfer-Wolf E, Charloux A et al (2001) Non-invasive cardiac output evaluation during a maximal progressive exercise test, using a new impedance cardiograph device. Eur J Appl Physiol 85:202–207

    Article  PubMed  CAS  Google Scholar 

  • Snyder EM, Olson TP, Johnson BD, Frantz RP (2008) Influence of sildenafil on lung diffusion during exposure to acute hypoxia at rest and during exercise in healthy humans. Eur J Appl Physiol. doi:10.1007/s00421-008-0735-5

  • Stenberg J, Ekblom B, Messin R (1966) Hemodynamic response to work at simulated altitude, 4,000 m. J Appl Physiol 21:1589–1594

    PubMed  CAS  Google Scholar 

  • Supuran CT, Mastrolorenzo A, Barbaro G, Scozzafava A (2006) Phosphodiesterase 5 inhibitors—Drug design and differentiation based on selectivity, pharmacokinetic and efficacy profiles. Curr Pharm Des 12:3459–3465. doi:10.2174/138161206778343118

    Article  PubMed  CAS  Google Scholar 

  • Walker DK, Ackland MJ, James GC et al (1999) Pharmacokinetics and metabolism of sildenafil in mouse, rat, rabbit, dog and man. Xenobiotica 29:297–310

    Article  PubMed  CAS  Google Scholar 

  • Weir EK, Archer SL (1995) The mechanism of acute hypoxic pulmonary vasoconstriction: the tale of two channels. FASEB J 9:183–189

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank the participants as well as Richard Viskochil, Katie Chamberlain, and Steve Hwang for their time and efforts. In addition, we thank Sonia Mora for handling the drug treatments. This study was funded by the World Anti-Doping Agency.

Conflict of interest

No conflict of interest present.

Author information

Authors and Affiliations

  1. Department of Kinesiology and Sport Sciences, University of Miami, 5202 University Drive, 315 Merrick Building, Coral Gables, FL, 33146, USA

    Jochen Kressler, Mark Stoutenberg, Bernard A. Roos, Arlette C. Perry, Joseph F. Signorile & Kevin A. Jacobs

  2. Miller School of Medicine, Geriatrics Institute, University of Miami, Miami, FL, 33136, USA

    Bernard A. Roos

  3. Geriatric Research, Education, and Clinical Center, Bruce W. Carter Veterans Affairs Medical Center, Miami, FL, 33125, USA

    Bernard A. Roos & Joseph F. Signorile

  4. Stanford University, Stanford Center on Longevity, Palo Alto, CA, 94305, USA

    Anne L. Friedlander

Authors
  1. Jochen Kressler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark Stoutenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernard A. Roos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anne L. Friedlander
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arlette C. Perry
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joseph F. Signorile
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kevin A. Jacobs
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kevin A. Jacobs.

Additional information

Communicated by Keith Phillip George.

This study involved the administration of a prescription drug. Accordingly, it was under the supervision of properly licensed medical professionals. In no way do the authors advocate any usage of this drug in any form or circumstance other than under such supervision.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kressler, J., Stoutenberg, M., Roos, B.A. et al. Sildenafil does not improve steady state cardiovascular hemodynamics, peak power, or 15-km time trial cycling performance at simulated moderate or high altitudes in men and women. Eur J Appl Physiol 111, 3031–3040 (2011). https://doi.org/10.1007/s00421-011-1930-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-011-1930-3

Keywords

Search

Navigation