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

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 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 02 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.

Figures

Fig. 1

cGMP at rest and at peak exercise with normoxia, hypoxia with placebo, and hypoxia with sildenafil. Grey bars represent resting data while black bars represent peak exercise data. *P < 0.05 sildenafil versus placebo. Bars represent SEM

Fig. 2

Diffusing capacity of the lung for carbon monoxide and components at rest, during exercise, and during recovery with normoxia, hypoxia and placebo, hypoxia and sildenafil. The top panel represents DLCO, followed by a panel representing DLNO, and a panel representing the DLNO to DLCO ratio with the final two panels representing pulmonary Capillary blood volume (Vc), and alveolar–capillary membrane conductance (DM). Filled black squares represent the normoxic condition, open diamonds represent the hypoxia with placebo condition, and filled circles represent the hypoxia with sildenafil condition. †P < 0.05 compared to normoxia. *P < 0.05 sildenafil versus placebo. Bars represent SEM

Fig. 3

Alveolar–capillary membrane conductance relative to pulmonary capillary blood volume at rest, during exercise and during recovery with normoxia, hypoxia with placebo and hypoxia with sildenafil. Filled black squares represents normoxic condition, open diamonds represents hypoxia with placebo condition, and filled circles represents hypoxia with sildenafil condition. †P < 0.05 compared to normoxia. *P < 0.05 sildenafil versus placebo. Bars represent SEM