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 Vc, and alveolar - capillary membrane conductance DM) 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, Vc, and DM 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. VC was higher with exercise in the placebo group, and the difference in DM between sildenafil and placebo was significant only when corrected for changes in Vc (DM/Vc = 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 DM when corrected for changes in Vc during short-term hypoxic exposure with exercise.
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Acknowledgments This work was supported by a grant to Dr. Frantz from PWzer, 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 eVorts of the study participants. We would also like to thank the staV 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.
- Membrane diffusion
- Pulmonary blood volume