Skip to main content
SpringerLink
Log in

Right ventricular function with hypoxic exercise: effects of sildenafil

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

Abstract

The effect of sildenafil on right ventricular contractility in hypoxic exercise is unknown, whereas reports have shown that sildenafil is associated with a smaller increase in pulmonary vascular resistance and right ventricular systolic pressure (RVSP) with exercise at high altitude. The present study evaluates the changes induced by controlled hypoxia on right ventricular pressure and performance with and without sildenafil administration. Tricuspid annular isovolumic acceleration (IVA) and annular velocities were measured in 14 healthy subjects at rest and after maximal exercise in a cross-over, double blind placebo controlled trial in three situations: normoxia, normobaric hypoxia with, and normobaric hypoxia without the administration of 100 mg sildenafil. RVSP, assessed by Doppler echocardiography, was determined from the peak tricuspid regurgitation pressure gradient. RVSP during rest increased from 26.9 ± 2.3 mmHg in normoxia to 37.8 ± 6.9 mmHg in hypoxia, p < 0.01; sildenafil administration reduced RVSP in hypoxia to 30.5 ± 5.6, p < 0.01. Compared to normoxia at rest, IVA increased similarly with peak exercise in normoxia and hypoxiasildenafil (by 2.37 and 1.90 m/s2, respectively), but the observed increase in IVA during exercise was smaller (0.86 m/s2, p < 0.05) in hypoxiaplacebo. Right ventricular contractility, as estimated by IVA at peak exercise is increased with the administration of sildenafil as compared to placebo, and is not different from the values seen during exercise in normoxia. This effect seems independent of the effect of sildenafil on RVSP.

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
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Abbas AE, Fortuin FD, Schiller NB, Appleton CP, Moreno CA, Lester SJ (2003) A simple method for noninvasive estimation of pulmonary vascular resistance. J Am Coll Cardiol 41:1021–1027

    Article  PubMed  Google Scholar 

  • Allemann Y, Rotter M, Hutter D, Lipp E, Sartori C, Scherrer U, Seiler C (2004) Impact of acute hypoxic pulmonary hypertension on LV diastolic function in healthy mountaineers at high altitude. Am J Physiol Heart Circ Physiol 286:H856–H862

    Article  PubMed  CAS  Google Scholar 

  • Allemann Y, Sartori C, Lepori M, Pierre S, Melot C, Naeije R, Scherrer U, Maggiorini M (2000) Echocardiographic and invasive measurements of pulmonary artery pressure correlate closely at high altitude. Am J Physiol Heart Circ Physiol 279: H2013–H2016

    PubMed  CAS  Google Scholar 

  • Arruda-Olson AM, Mahoney DW, Nehra A, Leckel M, Pellikka PA (2002) Cardiovascular effects of sildenafil during exercise in men with known or probable coronary artery disease: a randomized crossover trial. JAMA 287:719–725

    Article  PubMed  CAS  Google Scholar 

  • Balasubramanian V, Kaushik VS, Manchanda SC, Roy SB (1975) Effects of high altitude hypoxia on left ventricular systolic time intervals in man. Br Heart J 37:272–276

    Article  PubMed  CAS  Google Scholar 

  • Bell C, Monahan KD, Donato AJ, Hunt BE, Seals DR, Beck KC (2003) Use of acetylene breathing to determine cardiac output in young and older adults. Med Sci Sports Exerc 35:58–64

    Article  PubMed  CAS  Google Scholar 

  • Borg GA (1982) Psychophysical bases of perceived exertion. Med Sci Sports Exerc 14:377–381

    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 

  • Capen RL, Wagner WW Jr (1982) Intrapulmonary blood flow redistribution during hypoxia increases gas exchange surface area. J Appl Physiol 52:1575–1580

    PubMed  CAS  Google Scholar 

  • Cornolo J, Mollard P, Brugniaux JV, Robach P, Richalet JP (2004) Autonomic control of the cardiovascular system during acclimatization to high altitude: effects of sildenafil. J Appl Physiol 97:935–940

    Article  PubMed  CAS  Google Scholar 

  • Cremers B, Scheler M, Maack C, Wendler O, Schafers HJ, Sudkamp M, Bohm M (2003) Effects of sildenafil (viagra) on human myocardial contractility, in vitro arrhythmias, and tension of internal mammaria arteries and saphenous veins. J Cardiovasc Pharmacol 41:734–743

    Article  PubMed  CAS  Google Scholar 

  • Fesler P, Pagnamenta A, Rondelet B, Kerbaul F, Naeije R (2006) Effects of sildenafil on hypoxic pulmonary vascular function in dogs. J Appl Physiol 101:1085–1090

    Article  PubMed  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, Olschewski H, Schermuly RT, Weissmann N, Seeger W, Grimminger F (2002) Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Ann Intern Med 136:515–522

    PubMed  CAS  Google Scholar 

  • Ghofrani HA, Schermuly RT, Rose F, Wiedemann R, Kohstall MG, Kreckel A, Olschewski H, Weissmann N, Enke B, Ghofrani S, Seeger W, Grimminger F (2003) Sildenafil for long-term treatment of nonoperable chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med 167:1139–1141

    Article  PubMed  Google Scholar 

  • Ghofrani HA, Reichenberger F, Kohstall MG, Mrosek EH, Seeger T, Olschewski H, Seeger W, Grimminger F (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 

  • Ghofrani HA, Voswinckel R, Reichenberger F, Weissmann N, Schermuly RT, Seeger W, Grimminger F (2006) Hypoxia- and non-hypoxia-related pulmonary hypertension—established and new therapies. Cardiovasc Res 72:30–40

    Article  PubMed  CAS  Google Scholar 

  • Grunig E, Mereles D, Hildebrandt W, Swenson ER, Kubler W, Kuecherer H, Bartsch P (2000) Stress Doppler echocardiography for identification of susceptibility to high altitude pulmonary edema. J Am Coll Cardiol 35:980–987

    Article  PubMed  CAS  Google Scholar 

  • Hirata K, Adji A, Vlachopoulos C, O’Rourke MF (2005) Effect of sildenafil on cardiac performance in patients with heart failure. Am J Cardiol 96:1436–1440

    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

    Article  PubMed  CAS  Google Scholar 

  • Huez S, Retailleau K, Unger P, Pavelescu A, Vachiery JL, Derumeaux G, Naeije R (2005) Right and left ventricular adaptation to hypoxia: a tissue Doppler imaging study. Am J Physiol Heart Circ Physiol 289: H1391–H1398

    Article  PubMed  CAS  Google Scholar 

  • Huez S, Faoro V, Vachiery JL, Unger P, Martinot JB, Naeije R (2007) Images in cardiovascular medicine. High-altitude-induced right-heart failure. Circulation 115: e308–e309

    Article  PubMed  Google Scholar 

  • Johnson BD, Beck KC, Proctor DN, Miller J, Dietz NM, Joyner MJ (2000) Cardiac output during exercise by the open circuit acetylene washin method: comparison with direct Fick. J Appl Physiol 88:1650–1658

    Article  PubMed  CAS  Google Scholar 

  • Kaul S, Tei C, Hopkins JM, Shah PM (1984) Assessment of right ventricular function using two-dimensional echocardiography. Am Heart J 107:526–531

    Article  PubMed  CAS  Google Scholar 

  • Kitabatake A, Inoue M, Asao M, Masuyama T, Tanouchi J, Morita T, Mishima M, Uematsu M, Shimazu T, Hori M, Abe H (1983) Noninvasive evaluation of pulmonary hypertension by a pulsed Doppler technique. Circulation 68:302–309

    PubMed  CAS  Google Scholar 

  • Kjaergaard J, Petersen CL, Kjaer A, Schaadt BK, Oh JK, Hassager C (2006a) Evaluation of right ventricular volume and function by 2D and 3D echocardiography compared to MRI. Eur J Echocardiogr 7:430–438

    Article  PubMed  Google Scholar 

  • Kjaergaard J, Snyder EM, Hassager C, Oh JK, Johnson BD (2006b) Impact of preload and after-load on global and regional right ventricular function and pressure: a quantitative echocardiography study. J Am Soc Echocardiogr 19:515–521

    Article  PubMed  Google Scholar 

  • Kjaergaard J, Snyder EM, Hassager C, Olson TP, Oh JK, Johnson BD (2006c) The effect of 18 h of simulated high altitude on left ventricular function. Eur J Appl Physiol 98:411–418

    Article  PubMed  Google Scholar 

  • Maggiorini M, Melot C, Pierre S, Pfeiffer F, Greve I, Sartori C, Lepori M, Hauser M, Scherrer U, Naeije R (2001) High-altitude pulmonary edema is initially caused by an increase in capillary pressure. Circulation 103:2078–2083

    PubMed  CAS  Google Scholar 

  • McConnell MV, Solomon SD, Rayan ME, Come PC, Goldhaber SZ, Lee RT (1996) Regional right ventricular dysfunction detected by echocardiography in acute pulmonary embolism. Am J Cardiol 78:469–473

    Article  PubMed  CAS  Google Scholar 

  • McIntyre KM, Sasahara AA (1971) The hemodynamic response to pulmonary embolism in patients without prior cardiopulmonary disease. Am J Cardiol 28:288–294

    Article  Google Scholar 

  • Meluzin J, Spinarova L, Bakala J, Toman J, Krejci J, Hude P, Kara T, Soucek M (2001) Pulsed Doppler tissue imaging of the velocity of tricuspid annular systolic motion; a new, rapid, and non-invasive method of evaluating right ventricular systolic function. Eur Heart J 22:340–348

    Article  PubMed  CAS  Google Scholar 

  • Michelakis E, Tymchak W, Lien D, Webster L, Hashimoto K, Archer S (2002) Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide. Circulation 105:2398–2403

    Article  PubMed  CAS  Google Scholar 

  • Quinones MA, Otto CM, Stoddard M, Waggoner A, Zoghbi WA (2002) Recommendations for quantification of Doppler echocardiography: a report from the Doppler quantification task force of the nomenclature and standards committee of the American society of echocardiography. J Am Soc Echocardiogr 15:167–184

    Article  PubMed  Google Scholar 

  • Ricart A, Maristany J, Fort N, Leal C, Pages T, Viscor G (2005) Effects of sildenafil on the human response to acute hypoxia and exercise. High Alt Med Biol 6:43–49

    Article  PubMed  CAS  Google Scholar 

  • Richalet JP, Gratadour P, Robach P, Pham I, Dechaux M, Joncquiert-Latarjet A, Mollard P, Brugniaux J, Cornolo J (2005) Sildenafil inhibits altitude-induced hypoxemia and pulmonary hypertension. Am J Respir Crit Care Med 171:275–281

    Article  PubMed  Google Scholar 

  • Sebkhi A, Strange JW, Phillips SC, Wharton J, Wilkins MR (2003) Phosphodiesterase type 5 as a target for the treatment of hypoxia-induced pulmonary hypertension. Circulation 107:3230–3235

    Article  PubMed  CAS  Google Scholar 

  • Suarez J, Alexander JK, Houston CS (1987) Enhanced left ventricular systolic performance at high altitude during Operation Everest II. Am J Cardiol 60:137–142

    Article  PubMed  CAS  Google Scholar 

  • Vogel M, Schmidt MR, Kristiansen SB, Cheung M, White PA, Sorensen K, Redington AN (2002) Validation of myocardial acceleration during isovolumic contraction as a novel noninvasive index of right ventricular contractility: comparison with ventricular pressure–volume relations in an animal model. Circulation 105:1693–1699

    Article  PubMed  Google Scholar 

  • Zhao L, Mason NA, Morrell NW, Kojonazarov B, Sadykov A, Maripov A, Mirrakhimov MM, Aldashev A, Wilkins MR (2001) Sildenafil inhibits hypoxia-induced pulmonary hypertension. Circulation 104:424–428

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Study coordinators Minelle Hulsebus and Kathy O’Malley are thanked for their devoted work to the recruitment and data collection, and sonographer Jo-Ellen Ehrsam RDCS is acknowledged for her efforts in acquiring the echocardiographic images. This work was supported by American Heart Association, grants no. AHA0410073Z and AHA05-25727Z-01; and Mayo Clinic CTSA Clinical Research Unit, NCRR/NIH # M01-RR00585, and Pfizer Inc. The Danish Heart Foundation supported the research fellowship of Dr. Kjaergaard, grant no. 04-10-B109-A166-22192.

Author information

Authors and Affiliations

  1. Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Jesper Kjaergaard & Christian Hassager

  2. Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA

    Jesper Kjaergaard, Eric M. Snyder, Thomas P. Olson, Jae K. Oh, Bruce D. Johnson & Robert P. Frantz

Authors
  1. Jesper Kjaergaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eric M. Snyder
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christian Hassager
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas P. Olson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jae K. Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bruce D. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Robert P. Frantz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jesper Kjaergaard.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kjaergaard, J., Snyder, E.M., Hassager, C. et al. Right ventricular function with hypoxic exercise: effects of sildenafil. Eur J Appl Physiol 102, 87–95 (2007). https://doi.org/10.1007/s00421-007-0560-2

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-007-0560-2

Keywords

Search

Navigation