Sildenafil for primary and secondary pulmonary hypertension.
BACKGROUND
Sildenafil is a selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase type 5, an enzyme that is abundant in both lung and penile tissues. Sildenafil is widely used to dilate penile arteries, suggesting that it may also dilate pulmonary arteries in patients with pulmonary hypertension. However, the long-term hemodynamic effects and safety of the drug in pulmonary hypertension are not known.


METHODS
One patient with primary pulmonary hypertension and another with secondary pulmonary hypertension caused by collagen disease were given 50 mg oral sildenafil during cardiac catheterization for assessment of the acute hemodynamic effects of the drug. The patients were then given maintenance treatment with 25 mg oral sildenafil twice a day. Long-term hemodynamic effects were evaluated by repeated cardiac catheterization after 3 months, with the last oral dose given 15 hours before the procedure. The acute hemodynamic effects of sildenafil after the long-term treatment were studied during the same cardiac catheterization.


RESULTS
Sildenafil did not affect aortic pressure, but it significantly decreased pulmonary artery pressure and increased cardiac index, thereby reducing pulmonary vascular resistance. Long-term maintenance therapy with 25 mg oral sildenafil twice a day remarkably improved the clinical condition of the patients, without causing any adverse effects; New York Heart Association functional classification returned to class II (from class III). The acute efficacy of sildenafil was well preserved after the long-term treatment; there was no tolerance.


CONCLUSIONS
The data strongly suggest that sildenafil can be used as a valuable pulmonary vasodilator in patients with pulmonary hypertension, with good long-term hemodynamic effects and safety. The results necessitate larger trials to confirm these observations in a larger cohort of patients.
Watanabe
Hiroshi
H
Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. hwat@hama-med.ac.jp
Ohashi
Kyoichi
K
Takeuchi
Kazuhiko
K
Yamashita
Kazuhiro
K
Yokoyama
Taku
T
Tran
Quang-Kim
QK
Satoh
Hiroshi
H
Terada
Hajime
H
Ohashi
Hiroyuki
H
Hayashi
Hideharu
H
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000328:Adult; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects / Q000502:physiology; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D013995:Time; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases