Concepción Gistau

Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension.

RATIONALE 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. OBJECTIVES 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. MEASUREMENTS AND MAIN 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).

Effects of nebulized NG-nitro-L-arginine methyl ester in patients with hepatopulmonary syndrome†‡

Enhanced pulmonary production of nitric oxide (NO) has been implicated in the pathogenesis of hepatopulmonary syndrome (HPS). NO inhibition with NG‐nitro‐L‐arginine methyl ester (L‐NAME) in both animals and humans with HPS has improved arterial hypoxemia. We assessed the role of enhanced NO production in the pathobiology of arterial deoxygenation in HPS and the potential therapeutic efficacy of selective pulmonary NO inhibition. We investigated the effects of nebulized L‐NAME (162.0 mg) at 30 and 120 minutes on all intrapulmonary and extrapulmonary factors governing pulmonary gas exchange in 10 patients with HPS (60 ± 7 [SD] yr; alveolar–arterial oxygen gradient, range 19–76 mm Hg; arterial oxygen tension, range 37–89 mm Hg). Nebulized L‐NAME maximally decreased exhaled NO (by −55%; P < .001), mixed venous nitrite/nitrate (by −12%; P = .02), and cardiac output (by −11%; P = .002) while increased systemic vascular resistance (by 11%; P = .008) and pulmonary vascular resistance (by 25%; P = .03). In contrast, ventilation‐perfusion mismatching, intrapulmonary shunt and, in turn, arterial deoxygenation remained unchanged. In conclusion, gas exchange disturbances in HPS may be related to pulmonary vascular remodeling rather than to an ongoing vasodilator effect of enhanced NO production. (HEPATOLOGY 2006;43:1084–1091.)

Lung Function Abnormalities are Highly Frequent in Patients with Heart Failure and Preserved Ejection Fraction

BACKGROUND Heart failure with preserved ejection fraction (HFPEF) is the most prevalent form of heart failure in outpatients. Yet, the pathophysiology of this syndrome is unclear and pharmacological treatment does not improve prognosis. Because breathlessness during activities of daily living is the most frequent complaint of patients with HFPEF, we hypothesised that lung function may be often abnormal in these patients due to either a direct effect of HFPEF and/or shared risk factors. In this study we explore the frequency, type and severity of lung function abnormalities in HFPEF. METHODS We measured forced spirometry, static lung volumes, pulmonary diffusing capacity (DL(CO)) and arterial blood gases in 69 outpatients with newly diagnosed symptomatic HFPEF. RESULTS We found that 94% of the patients showed abnormalities in at least one of the lung function measurements obtained: spirometry was abnormal in 59%, DL(CO) in 83% and arterial hypoxaemia was present in 62%. Their severity varied between patients, they were more prevalent in patients with NYHA functional class III/IV, and most often they were undiagnosed and untreated. CONCLUSIONS Lung function abnormalities are very frequent in HFPEF patients. A greater awareness among clinicians may contribute to improve their management and health status.

Ventilation/Perfusion Distribution Abnormalities In Morbidly Obese Subjects Before and After Bariatric Surgery

BACKGROUND Obesity is a global and growing public health problem. Bariatric surgery (BS) is indicated in patients with morbid obesity. To our knowledge, the effects of morbid obesity and BS on ventilation/perfusion (V.a/Q.) ratio distributions using the multiple inert gas elimination technique have never before been explored. METHODS We compared respiratory and inert gas (V.a/Q. ratio distributions) pulmonary gas exchange, breathing both ambient air and 100% oxygen, in 19 morbidly obese women (BMI, 45 kg/m2), both before and 1 year after BS, and in eight normal-weight, never smoker, age-matched, healthy women. RESULTS Before BS, morbidly obese individuals had reduced arterial Po2 (76 ± 2 mm Hg) and an increased alveolar-arterial Po2 difference (27 ± 2 mm Hg) caused by small amounts of shunt (4.3% ± 1.1% of cardiac output), along with abnormally broadly unimodal blood flow dispersion (0.83 ± 0.06). During 100% oxygen breathing, shunt increased twofold in parallel with a reduction of blood flow to low V.a/Q. units, suggesting the development of reabsorption atelectasis without reversion of hypoxic pulmonary vasoconstriction. After BS, body weight was reduced significantly (BMI, 31 kg/m2), and pulmonary gas exchange abnormalities were decreased. CONCLUSIONS Morbid obesity is associated with mild to moderate shunt and V.a/Q. imbalance. These abnormalities are reduced after BS.

Different dyspnoea perception in COPD patients with frequent and infrequent exacerbations

Background Some patients with COPD report frequent acute exacerbations (AECOPD) of the disease (FE), whereas others suffer them infrequently (IE). Because the current diagnosis of exacerbation relies on patients perception of increased symptoms (mostly dyspnoea), we hypothesised that dyspnoea perception might be different in COPD patients with FE (≥2 exacerbations or 1 hospitalisation due to AECOPD in the previous year) or IE (≤1 exacerbation in the previous year), AECOPD being defined by the institution antibiotics and/or steroids treatment, or hospital admission. Objective To test the hypothesis that dyspnoea perception is increased in FE and/or decreased in IE with COPD. Methods We compared the perception of dyspnoea (Borg scale), mouth occlusion pressure 0.1 s after the onset of inspiration (P0.1) and ventilatory response to hypercapnia (ΔVE/ΔPETCO2) in 34 clinically stable COPD patients with FE (n=14) or IE (n=20), with similar age, gender, body mass index and degree of airflow limitation. As a reference, we studied a group of age-matched healthy volunteers (n=10) with normal spirometry. Results At rest, P0.1 was higher in FE than IE and controls (p<0.01). Compared with controls, the ventilatory response to hypercapnia was equally blunted both in FE and IE (p<0.001). Despite similar spirometry, during rebreathing peak Borg score and ΔBorg were higher (p<0.01) in FE and lower (p<0.01) in IE, than in controls. Conclusions Dyspnoea perception during CO2 rebreathing is enhanced in FE and blunted in IE. These differences may contribute to the differential rate of reported exacerbations in FE and IE. Trial registration number NCT02113839.