Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension.
BACKGROUND
Sildenafil, a phosphodiesterase-5 inhibitor, could be useful for treating pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). However, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange in this condition.


OBJECTIVE
To assess the acute hemodynamic and gas exchange effects of sildenafil in patients with COPD-associated PH.


METHODS
We conducted a randomized, dose comparison trial in 20 patients with COPD-associated PH. Eleven patients were assigned to 20 mg, and 9 patients to 40 mg, of sildenafil. Pulmonary hemodynamics and gas exchange, including ventilation-perfusion (V(A)/Q) relationships, were assessed at rest and during constant-work rate exercise, before and 1 hour after sildenafil administration.


RESULTS
Both sildenafil doses reduced the mean pulmonary arterial pressure (PAP) at rest and during exercise, without differences between them. Overall, PAP decreased -6 mm Hg (95% confidence interval [95% CI], -7 to -4) at rest and -11 mm Hg (95% CI, -14 to -8) during exercise. After sildenafil, Pa(O(2)) decreased -6 mm Hg (95% CI, -8 to -4) at rest because of increased perfusion in units with low V(A)/Q ratio, without differences between doses. No change in Pa(O(2)) (95% CI, -3 to 0.2 mm Hg) or V(A)/Q relationships occurred during exercise after sildenafil. Changes induced by sildenafil in Pa(O(2)) and V(A)/Q distributions at rest correlated with their respective values at baseline.


CONCLUSIONS
In patients with COPD-associated PH, sildenafil improves pulmonary hemodynamics at rest and during exercise. This effect is accompanied by the inhibition of hypoxic vasoconstriction, which impairs arterial oxygenation at rest. The use of sildenafil in COPD should be done cautiously and under close monitoring of blood gases. Clinical trial registered with www.clinicaltrials.gov (NCT00491803).
Blanco
Isabel
I
Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona.
Gimeno
Elena
E
Munoz
Phillip A
PA
Pizarro
Sandra
S
Gistau
Concepción
C
Rodriguez-Roisin
Robert
R
Roca
Josep
J
Barberà
Joan Albert
JA
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000368:Aged; D004305:Dose-Response Relationship, Drug; D015444:Exercise / Q000502:physiology; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects* / Q000502:physiology; D011669:Pulmonary Wedge Pressure / Q000187:drug effects / Q000502:physiology; D011687:Purines / Q000008:administration & dosage / Q000627:therapeutic use; D012146:Rest / Q000502:physiology; D012720:Severity of Illness Index; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases