title: Long-term inhaled nitric oxide plus phosphodiesterase 5 inhibitors for severe pulmonary hypertension.
abstract: BACKGROUND
  Inhaled nitric oxide (iNO) is a potent pulmonary vasodilator, but therapeutic experience in patients with severe pulmonary hypertension is scarce.
  
  
  METHODS
  Eleven patients with severe pulmonary hypertension, 6 due to pulmonary arterial hypertension and 4 due to chronic thromboembolic disease, were selected for iNO therapy. A phosphodiesterase type 5 inhibitor (PDE5i) was added in cases of clinical worsening. In this study we evaluate the clinical effectiveness and safety of long-term treatment with iNO either alone or combined with a PDE5i.
  
  
  RESULTS
  After 1 month of iNO administration, improvements were observed in World Health Organization functional class, Borg scale (p = 0.003), brain natriuretic peptide levels (p = 0.002) and 6-minute walk test (p = 0.003). After 6 months of treatment, 7 patients had clinical deterioration that was reversed upon adding a PDE5i. One of these patients died in Month 8 and another underwent pulmonary transplantation in Month 9. The clinical condition of the remaining 9 patients was unchanged after 1 year. A second right catheterization showed improvement in mean pulmonary arterial pressure (66 +/- 15 mm Hg to 56 +/- 18 mm Hg; p = 0.01), pulmonary vascular resistance (1,234 +/- 380 dyn/s/cm(5) to 911 +/- 410 dyn/s/cm(5); p = 0.008) and cardiac index (2.0 +/- 0.4 liters/min/m(2) to 2.5 +/- 0.4 liters/min/m(2); p = 0.04). There was no significant increase in methemoglobin, no worsening of pulmonary function and no sudden withdrawal syndrome.
  
  
  CONCLUSIONS
  We suggest that iNO therapy alone or in combination with a PDE5i could be a therapeutic alternative for severe pulmonary hypertension.
authors.affiliation: Pneumology Unit, Hospital General de Gran Canaria Dr Negrín, Gran Canaria, Spain. gperpen@gobiernodecanarias.org
authors.forename: Gregorio Miguel
authors.initials: GM
authors.lastname: Pérez-Peñate
authors.forename: Gabriel
authors.initials: G
authors.lastname: Juliá-Serdà
authors.forename: Nazario
authors.initials: N
authors.lastname: Ojeda-Betancort
authors.forename: Antonio
authors.initials: A
authors.lastname: García-Quintana
authors.forename: Juan
authors.initials: J
authors.lastname: Pulido-Duque
authors.forename: Aurelio
authors.initials: A
authors.lastname: Rodríguez-Pérez
authors.forename: Pedro
authors.initials: P
authors.lastname: Cabrera-Navarro
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Gómez-Sánchez
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D006152:Cyclic GMP / Q000097:blood; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism*; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D012449:Safety; D013923:Thromboembolism / Q000150:complications; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D004232:Diuretics; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006152:Cyclic GMP