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Influence of sildenafil on lung diffusion during exposure to acute hypoxia at rest and during exercise in healthy humans

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Abstract

We sought to determine the influence of sildenafil on the diffusing capacity of the lungs for carbon monoxide (DLCO) and the components of DLCO (pulmonary capillary blood volume V c, and alveolar–capillary membrane conductance D M) at rest and following exercise with normoxia and hypoxia. This double-blind placebo-controlled, cross-over study included 14 healthy subjects (age = 33 ± 11 years, ht = 181 ± 8 cm, weight = 85 ± 14 kg, BMI = 26 ± 3 kg/m2, peak normoxic VO2 = 36 ± 6 ml/kg, mean ± SD). Subjects were randomized to placebo or 100 mg sildenafil 1 h prior to entering a hypoxic tent with an FiO2 of 12.5% for 90 min. DLCO, V c, and D M were assessed at rest, every 3 min during exercise, at peak exercise, and 10 and 30 min post exercise. Sildenafil attenuated the elevation in PAP at rest and during recovery with exposure to hypoxia, but pulmonary arterial pressure immediately post exercise was not different between sildenafil and placebo. Systemic O2 saturation and VO2peak did not differ between the two conditions. DLCO was not different between groups at any time point. V C was higher with exercise in the placebo group, and the difference in D M between sildenafil and placebo was significant only when corrected for changes in V c (D M/V c = 0.57 ± 0.29 vs. 0.41 ± 0.16, P = 0.04). These results suggest no effect of sildenafil on DLCO, but an improvement in D M when corrected for changes in V c during short-term hypoxic exposure with exercise.

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Acknowledgments

This work was supported by a grant to Dr. Frantz from Pfizer, Inc., NIH Grant HL71478, and AHA Grant 56051Z. At the time the study was performed Dr. Snyder was supported by the Mayo Clinic Nephrology and Hypertension Training Grant (DK007013-31). We would like to thank Minelle Hulsebus and Kathy O’Malley for their help with data collection, as well as the efforts of the study participants. We would also like to thank the staff of the General Clinical Research Center (GCRC) for their assistance throughout this study. The Mayo Clinic GCRC is supported by US Public Health Service grant M01-RR00585.

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Authors and Affiliations

  1. Department of Pharmacy Practice and Science, University of Arizona, 1703 E. Mabel, Tucson, AZ, 85721, USA

    Eric M. Snyder

  2. Cardiovascular Diseases, College of Medicine, Mayo Clinic, Rochester, MN, USA

    Thomas P. Olson, Bruce D. Johnson & Robert P. Frantz

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  1. Eric M. Snyder
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  2. Thomas P. Olson
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Correspondence to Eric M. Snyder.

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Snyder, E.M., Olson, T.P., Johnson, B.D. et al. Influence of sildenafil on lung diffusion during exposure to acute hypoxia at rest and during exercise in healthy humans. Eur J Appl Physiol 103, 421–430 (2008). https://doi.org/10.1007/s00421-008-0735-5

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