title: Acute and chronic effects of sildenafil in patients with pulmonary arterial hypertension.
abstract: Sildenafil and inhaled nitric oxide (iNO) relax smooth muscle by inhibiting the degradation and stimulating the production of cyclic guanosine monophosphate, respectively. We compared the acute pulmonary vasodilator effects of sildenafil, iNO, and epoprostenol and asked whether the combination of iNO with sildenafil had additive pulmonary vasodilator effects. We assessed the effects of extended use of sildenafil in a small cohort of patients. Twenty patients with pulmonary arterial hypertension underwent an acute vasodilator trial with sildenafil (all patients), iNO and iNO plus sildenafil (11), and epoprostenol (19). We also provided sildenafil to patients who were ineligible for, or had clinical deterioration on epoprostenol, treprostinil, or bosentan. Mean+/-se pulmonary artery pressure dropped by 13+/-3%, 19+/-4%, 14+/-3%, and 26+/-4% with epoprostenol, iNO, sildenafil, and iNO+sildenafil, respectively. Cardiac index increased with epoprostenol and sildenafil. A correlation was found between the effects of iNO and epoprostenol. Nine out of ten patients who were started on long-term sildenafil treatment alone or in combination with other vasodilators had symptomatic improvement. Three died of right heart failure. In conclusion, sildenafil is a potent acute pulmonary vasodilator, an effect that is potentiated by combination with iNO. Long-term therapy of pulmonary hypertension with sildenafil alone or in combination with other agents appears to be safe and well tolerated.
authors.affiliation: Department of Pulmonary, Critical Care and Sleep, Tufts-New England Medical Center, 750 Washington Street, Box #257, Boston, MA 0211, USA. ipreston@tufts-nemc.org
authors.forename: Ioana R
authors.initials: IR
authors.lastname: Preston
authors.forename: James R
authors.initials: JR
authors.lastname: Klinger
authors.forename: Jeanne
authors.initials: J
authors.lastname: Houtches
authors.forename: David
authors.initials: D
authors.lastname: Nelson
authors.forename: Harrison W
authors.initials: HW
authors.lastname: Farber
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hill
mesh_terms: D000280:Administration, Inhalation; D000704:Analysis of Variance; D002302:Cardiac Output / Q000187:drug effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000008:administration & dosage / Q000627:therapeutic use; D005080:Exercise Test; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use; D010879:Piperazines / Q000008:administration & dosage* / Q000627:therapeutic use; D011446:Prospective Studies; D011651:Pulmonary Artery; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D011464:Epoprostenol