Influence of sildenafil on lung diffusion during exposure to acute hypoxia at rest and during exercise in healthy humans.
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.
Snyder
Eric M
EM
Department of Pharmacy Practice and Science, University of Arizona, 1703 E. Mabel, Tucson, AZ 85721, USA. snyder@pharmacy.arizona.edu
Olson
Thomas P
TP
Johnson
Bruce D
BD
Frantz
Robert P
RP
D000208:Acute Disease; D000328:Adult; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D006152:Cyclic GMP / Q000097:blood; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood; D015444:Exercise / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010100:Oxygen / Q000097:blood; D010879:Piperazines / Q000008:administration & dosage*; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects / Q000502:physiology; D011687:Purines / Q000008:administration & dosage; D012146:Rest / Q000502:physiology; D000068677:Sildenafil Citrate; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D013450:Sulfones / Q000008:administration & dosage*; D014665:Vasodilator Agents / Q000008:administration & dosage*
D019332:Endothelin-1; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; D000068677:Sildenafil Citrate; D006152:Cyclic GMP; D010100:Oxygen