Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: Comparison with inhaled nitric oxide

The prognosis of patients with severe pulmonary hypertension (PHT) is poor. To determine prognosis and guide therapy, an acute hemodynamic trial of selective pulmonary vasodilators, usually inhaled nitric oxide (iNO), was performed. We hypothesized that oral sildenafil, a phosphodiesterase-5 inhibit...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2002-05, Vol.105 (20), p.2398-2403
Main Authors: MICHELAKIS, Evangelos, TYMCHAK, Wayne, LIEN, Dale, WEBSTER, Linda, HASHIMOTO, Kyoko, ARCHER, Stephen
Format: Article
Language:English
Subjects:
Administration, Oral
Adult
Biological and medical sciences
Cyclic GMP - blood
Diuretics - therapeutic use
Drug Therapy, Combination
Female
Headache - etiology
Hemodynamics - drug effects
Humans
Hypertension, Pulmonary - drug therapy
Hypertension, Pulmonary - physiopathology
Male
Medical sciences
Middle Aged
Nitric Oxide - administration & dosage
Pharmacology. Drug treatments
Phosphodiesterase Inhibitors - administration & dosage
Phosphodiesterase Inhibitors - adverse effects
Piperazines - administration & dosage
Piperazines - adverse effects
Predictive Value of Tests
Pulmonary Artery - drug effects
Pulmonary Artery - physiopathology
Pulmonary Circulation - drug effects
Pulmonary Wedge Pressure - drug effects
Purines
Respiratory system
Sildenafil Citrate
Sulfones
Treatment Outcome
Vascular Resistance - drug effects
Vasodilator Agents - administration & dosage
Vasodilator Agents - adverse effects
Warfarin - therapeutic use
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Summary:The prognosis of patients with severe pulmonary hypertension (PHT) is poor. To determine prognosis and guide therapy, an acute hemodynamic trial of selective pulmonary vasodilators, usually inhaled nitric oxide (iNO), was performed. We hypothesized that oral sildenafil, a phosphodiesterase-5 inhibitor, is a safe and effective alternative to iNO. We studied 13 consecutive patients (mean+/-SEM, 44+/-2 years of age; 9 women) referred for consideration of heart-lung transplantation or as a guide to medical therapy. All but one were functional class III or IV. Patients had primary PHT (n=9), pulmonary arterial hypertension (n=2), or secondary PHT (n=2). Hemodynamics and serum cyclic guanosine-monophosphate levels (cGMP) were measured at baseline and at peak effects of iNO (80 ppm), sildenafil (75 mg), and their combination. The decrease in pulmonary vascular resistance was similar with iNO (-19+/-5%) and sildenafil (-27+/-3%), whereas sildenafil+iNO was more effective than iNO alone (-32+/-5%, P
ISSN:0009-7322
1524-4539
DOI:10.1161/01.CIR.0000016641.12984.DC