Effect of sildenafil on hypoxia-induced changes in pulmonary circulation and right ventricular function

• Published in: Respiratory physiology & neurobiology Vol. 159; no. 2; pp. 196 - 201
• Main Authors: Reichenberger, Frank, Kohstall, Markus G., Seeger, Timon, Olschewski, Horst, Grimminger, Friedrich, Seeger, Werner, Ghofrani, Hossein A.
• Format: Journal Article
• Language: English
• Published: Amsterdarm Elsevier B.V 15.11.2007; Elsevier
• Subjects: Adult; Altitude; Biological and medical sciences; Double-Blind Method; Echocardiography; Echocardiography, Doppler - methods; Female; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Humans; Hypoxia; Hypoxia - drug therapy; Hypoxia - physiopathology; Male; Medical Education; Middle Aged; Mountaineering - physiology; Piperazines - therapeutic use; Pulmonary circulation; Pulmonary Circulation - drug effects; Pulmonary/Respiratory; Purines - therapeutic use; Right ventricular function; Sildenafil; Sildenafil Citrate; Sulfones - therapeutic use; Vasodilator Agents - therapeutic use; Ventricular Function, Right - drug effects; Vertebrates: respiratory system; Hypoxia; Pulmonary circulation; Echocardiography; Sildenafil; Right ventricular function; Oxygen; 3',5'-Cyclic-GMP phosphodiesterase; Enzyme; Enzyme inhibitor; Esterases; Phosphoric diester hydrolases; Respiratory system; Vertebrata; Mammalia; Hydrolases
• ISSN: 1569-9048; 1878-1519
• DOI: 10.1016/j.resp.2007.07.005

Hypoxia leads to pulmonary vasoconstriction in healthy men. However, the consequences on right ventricular function are not known. The effects of hypoxia on systolic pulmonary artery pressure (sPAP) and right ventricular function index (TEI) were assessed by Doppler echocardiography. Fourteen members of a Mount Everest expedition were monitored during acute hypoxic challenge at sea level, environmental hypoxia exposure at altitudes of 3440 m and 5245 m and 2 weeks after return to sea level. Subjects received either placebo or 50 mg sildenafil in a double-blind randomised cross-over design. Under normoxia at baseline, mean sPAP was 17.1(S.E.M. 1.3) mm Hg, and TEI was 0.13(0.004). Both increased during acute hypoxia: sPAP 29.6(2.6) mm Hg, and TEI 0.35(0.06) (each p < 0.01). At 5245 m sPAP was 29.1(1.7) and TEI was 0.43(0.05) in the placebo group, while in the sildenafil group, both sPAP and TEI were reduced to 22(1.5) mm Hg and 0.23(0.03) (each p < 0.005), respectively. We conclude that in healthy individuals, exposure to acute hypoxia and sojourns at high altitude result in a small but significant increase in sPAP accompanied by an impairment of right ventricular function. Sildenafil significantly decreases sPAP and improves right ventricular function.