title: Effect of sildenafil on ventilatory efficiency and exercise tolerance in pulmonary hypertension.
abstract: BACKGROUND
  The pulmonary vasculopathy in pulmonary arterial hypertension (PAH) results in increased resistance to pulmonary blood flow, limiting the cardiac output required for the increased O(2) demands of exercise.
  
  
  OBJECTIVE
  We sought to determine the physiologic basis for clinical improvement in PAH patients receiving sildenafil, hypothesizing that the key mechanisms of improvement are improved blood flow and ventilatory efficiency, leading to improved exercise capacity and O(2) pulse over time.
  
  
  METHODS
  We studied 28 PAH patients with (n=14) and without (n=14) sildenafil treatment. All received warfarin and diuretic therapy, and 13/14 sildenafil-treated patients were already receiving specific PAH drugs. Cardiopulmonary exercise testing was performed before and after sildenafil.
  
  
  RESULTS
  Peak VO2 , peak O(2) pulse, V E/CO2 and PETCO2, were 0.84+/-0.1 L/min, 6.1+/-0.7 mL beat(- 1), 49+/-2 and 26+/-1.5 mm Hg, and improved after adding sildenafil to 0.91+/-0.1 L/min, 6.8+/-0.8 mL beat(- 1), 43+/-2, and 30+/-1.9, respectively, whereas control patients worsened (p=0.012, 0.008, 0.008 and 0.0002, treated vs. controls, respectively).
  
  
  CONCLUSIONS
  Sildenafil improves PETCO2, V E/V CO(2), peak O2 pulse and peak VO2 during exercise compared to controls. A prospective, placebo-controlled study is needed to validate these findings.
authors: Division of Cardiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA. oudiz@humc.edu
authors: Ronald J
authors: RJ
authors: Oudiz
authors: Giorgio
authors: G
authors: Roveran
authors: James E
authors: JE
authors: Hansen
authors: Xing-Guo
authors: XG
authors: Sun
authors: Karlman
authors: K
authors: Wasserman
mesh_terms: D000328:Adult; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D012123:Pulmonary Ventilation / Q000187:drug effects*; D011687:Purines / Q000627:therapeutic use; D012129:Respiratory Function Tests; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate
references: Heart. 2006 Dec;92(12):1860-1
references: 17105892
references: Eur J Clin Invest. 2006 Sep;36 Suppl 3:32-8
references: 16919008
references: N Engl J Med. 2005 Nov 17;353(20):2148-57
references: 16291984
references: Chest. 2005 May;127(5):1637-46
references: 15888840
references: Eur Respir J. 2007 Mar;29(3):469-75
references: 17079256
references: Int J Cardiol. 2007 Jul 31;119(3):400-2
references: 17064789
references: Int J Cardiol. 2007 Sep 3;120(3):306-13
references: 17174417
references: Eur Respir J. 2004 Dec;24(6):1007-10
references: 15572546
references: Clin Sci (Lond). 1957 May;16(2):325-50
references: 13427191
references: Clin Sci (Lond). 1954 Nov;13(4):511-33
references: 13209837
references: Cathet Cardiovasc Diagn. 1994;Suppl 2:61-8
references: 7994743
references: J Appl Physiol (1985). 1986 Jun;60(6):2020-7
references: 3087938
references: Am Rev Respir Dis. 1975 Aug;112(2):219-49
references: 239617
references: N Engl J Med. 2004 Oct 14;351(16):1655-65
references: 15483284
references: N Engl J Med. 2004 Sep 30;351(14):1425-36
references: 15459304
references: Chest. 2004 Jul;126(1 Suppl):14S-34S
references: 15249493
references: Am J Respir Crit Care Med. 2004 Feb 15;169(4):441-7
references: 14630619
references: Circulation. 2001 Jul 24;104(4):429-35
references: 11468205