Effect of sildenafil on ventilatory efficiency and exercise tolerance in pulmonary hypertension.
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.
Oudiz
Ronald J
RJ
Division of Cardiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA. oudiz@humc.edu
Roveran
Giorgio
G
Hansen
James E
JE
Sun
Xing-Guo
XG
Wasserman
Karlman
K
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*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate
Heart. 2006 Dec;92(12):1860-1
17105892
Eur J Clin Invest. 2006 Sep;36 Suppl 3:32-8
16919008
N Engl J Med. 2005 Nov 17;353(20):2148-57
16291984
Chest. 2005 May;127(5):1637-46
15888840
Eur Respir J. 2007 Mar;29(3):469-75
17079256
Int J Cardiol. 2007 Jul 31;119(3):400-2
17064789
Int J Cardiol. 2007 Sep 3;120(3):306-13
17174417
Eur Respir J. 2004 Dec;24(6):1007-10
15572546
Clin Sci (Lond). 1957 May;16(2):325-50
13427191
Clin Sci (Lond). 1954 Nov;13(4):511-33
13209837
Cathet Cardiovasc Diagn. 1994;Suppl 2:61-8
7994743
J Appl Physiol (1985). 1986 Jun;60(6):2020-7
3087938
Am Rev Respir Dis. 1975 Aug;112(2):219-49
239617
N Engl J Med. 2004 Oct 14;351(16):1655-65
15483284
N Engl J Med. 2004 Sep 30;351(14):1425-36
15459304
Chest. 2004 Jul;126(1 Suppl):14S-34S
15249493
Am J Respir Crit Care Med. 2004 Feb 15;169(4):441-7
14630619
Circulation. 2001 Jul 24;104(4):429-35
11468205