Acute effects of sildenafil on exercise pulmonary hemodynamics and capacity in patients with COPD.
BACKGROUND
We investigated in chronic obstructive pulmonary disease (COPD) patients whether a single dose of sildenafil can attenuate the exercise-induced increase in pulmonary artery pressure, thereby allowing augmentation of stroke volume (SV), and improving maximal exercise capacity.


METHODS
Eighteen COPD patients (GOLD II-IV) underwent right heart catheterization at rest and submaximal exercise. Mean pulmonary artery pressure (mPpa) and cardiac output (CO) were assessed. Resting and exercise measurements were repeated 60 min after oral intake of 50mg sildenafil. Also, on different days, patients performed two maximal exercise tests (CPET) randomly, 1h after placebo and after 50mg sildenafil.


RESULTS
Five COPD patients had pulmonary hypertension (PH) at rest (mPpa >25 mmHg) and six developed PH during exercise (mPpa >30 mmHg). In all patients, mPpa increased from rest to submaximal exercise (23+/-10-35+/-14 mmHg). After sildenafil mPpa at rest was 20+/-10 mmHg, in exercise mPpa was increased less to 30+/-14 mmHg (p<0.01). The reduced augmentation in mPpa was not accompanied by an increased SV and CO. In COPD patients with PH the percentage increase in mPpa to submaximal exercise was 68% before, and 51% after oral intake of sildenafil (p=0.07). In COPD without PH, these values were 46% and 41% (ns), respectively. Maximal exercise capacity and CPET characteristics were unchanged after sildenafil.


CONCLUSIONS
Regardless of mPpa at rest, sildenafil attenuates the increase in mPpa during submaximal exercise in COPD. This attenuated increase is neither accompanied by enhanced SV and CO, nor by improved maximal exercise capacity.
Holverda
Sebastiaan
S
Department of Pulmonary Diseases, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
Rietema
Heleen
H
Bogaard
Harm J
HJ
Westerhof
Nico
N
Postmus
Pieter E
PE
Boonstra
Anco
A
Vonk-Noordegraaf
Anton
A
D000368:Aged; D015308:Anaerobic Threshold / Q000187:drug effects / Q000502:physiology; D006328:Cardiac Catheterization; D002302:Cardiac Output / Q000187:drug effects; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010879:Piperazines / Q000627:therapeutic use*; D011652:Pulmonary Circulation / Q000187:drug effects*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011687:Purines / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013318:Stroke Volume / Q000187:drug effects; D013450:Sulfones / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*; D016278:Ventricular Function, Right / Q000187:drug effects
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D010100:Oxygen