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Portopulmonary hypertension (PoPH) is a serious condition without an established treatment. Drugs used to treat pulmonary hypertension may have detrimental effects on portal hypertension. This study was designed to assess in patients with PoPH the acute effects of inhaled iloprost (iILO) on pulmonary and hepatic hemodynamics and to evaluate the clinical outcome after 12 months of treatment. We conducted 2 separate studies. In the first one, 21 patients with PoPH were acutely tested with 2.8 microg of iILO. Pulmonary and hepatic hemodynamics were assessed at the baseline and through 60 minutes after iILO. In the second one, we retrospectively evaluated 12 patients treated with iILO (30 microg/day) for more than 1 year. The 6-minute walk distance (6MWD), functional class (FC), and echocardiogram were analyzed at the baseline and after 12 months of treatment. In the acute study, iILO rapidly reduced pulmonary artery pressure (PAP; -16% + or - 8%, P < 0.001) and pulmonary vascular resistance (-18% + or - 14%, P < 0.001). The cardiac output did not change initially but decreased after 30 minutes. The hepatic venous pressure gradient (HVPG) and hepatic blood flow did not vary through the study. Pulmonary vasodilation induced by iILO was inversely related to HVPG. In the long-term evaluation, iILO improved FC by 1 or more in 7 patients (P = 0.04) and increased 6MWD by 67 + or - 59 m at 12 months (P < 0.001). No change in systolic PAP was observed. Two patients died because of hepatic complications, and 4 additional patients presented clinically significant events that were related to hepatic disease in 2 and worsening of pulmonary hypertension in 2. We conclude that in patients with PoPH, iILO produces rapid and selective pulmonary vasodilation without altering the hepatic hemodynamics. Its long-term use may provide sustained improvements in symptoms and exercise tolerance in some patients with PoPH. A randomized, controlled trial is warranted to establish its clinical role in this serious condition.

The role of acute pulmonary vasodilator testing in portopulmonary hypertension (PoPH), a current contraindication for orthotopic liver transplantation (OLT), has not been thoroughly elucidated. The purpose of this work was to analyze the results of acute vasodilator testing with inhaled nitric oxide (NO), to compare them with intravenous epoprostenol (PGI(2)), and to investigate the acute effects of the oral vasodilator isosorbide-5-mononitrate (Is-5-MN), in patients with PoPH. A total of 19 patients with PoPH (male/female = 9/10) were studied. Pulmonary hemodynamic measurements were performed at baseline and during NO inhalation (40 ppm); additionally, 15 patients were tested with PGI(2) (2-12 mug/kg/minute) and 8 were tested with Is-5-MN (20-40 mg). Inhaled NO reduced pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) by 5.7% and 11.0%, respectively. PGI(2) elicited greater reductions in PAP (11.8%) and PVR (-24.0%), and produced a 28% drop in systemic vascular resistance (SVR) and a 17% increase in the cardiac index (CI). Is-5-MN reduced PAP by 25.6% and PVR by 21.5%, without systemic changes. There was good agreement between the response to PGI(2) and Is-5-MN: 6 patients of the whole series (32%) decreased PAP >20% from baseline, reaching a final value < or = 35 mmHg, the current limit for OLT. In conclusion, acute vasodilator testing has a relevant role in PoPH, as it identifies one-third of patients able to reach a more favorable hemodynamic situation, which can be determinant for their management. For vasodilator testing, PGI(2) is more suitable than NO in PoPH. Is-5-MN exerts a selective effect on pulmonary circulation in patients who had already responded to PGI(2).

Intimal enlargement of pulmonary arteries is an early change in chronic obstructive pulmonary disease (COPD). The cellular and extracellular components that are involved in this enlargement are unknown. The present study was designed to characterize the structural changes occurring in pulmonary muscular arteries in the initial disease stages. Lung specimens from patients with moderate COPD (n=8; forced expiratory volume in one second (FEV1), 66 +/- 10% predicted) and smokers without airflow obstruction (n=7; FEV1, 86 +/- 6% pred), were investigated by histochemistry to characterize extracellular matrix proteins and by immunohistochemistry to identify intrinsic cells of the vascular wall. In both COPD patients and smokers, the majority of cells present in the enlarged intimas were stained by specific smooth muscle cell (SMC) markers. No staining with endothelial or fibroblast markers was shown. A proportion of SMCs did not stain with desmin, suggesting cellular heterogeneity in this population. Elastin was the most abundant extracellular matrix protein and collagen was seen in a lower proportion. The amount of collagen was related to the intimal thickness (p

Lung volume reduction surgery (LVRS) improves lung function, respiratory symptoms, and exercise tolerance in selected patients with chronic obstructive pulmonary disease, who have heterogeneous emphysema. However, the reported effects of LVRS on gas exchange are variable, even when lung function is improved. To clarify how LVRS affects gas exchange in chronic obstructive pulmonary disease, 23 patients were studied before LVRS, 14 of whom were again studied afterwards. We performed measurements of lung mechanics, pulmonary hemodynamics, and ventilation-perfusion (V̇a/Q̇) inequality using the multiple inert-gas elimination technique. LVRS improved arterial Po2 (PaO2) by a mean of 6 Torr ( P = 0.04), with no significant effect on arterial Pco2 (PaCO2), but with great variability in both. Lung mechanical properties improved considerably more than did gas exchange. Post-LVRS PaO2 depended mostly on its pre-LVRS value, whereas improvement in PaO2 was explained mostly by improved V̇a/Q̇ inequality, with lesser contributions from both increased ventilation and higher mixed venous Po2. However, no index of lung mechanical properties correlated with PaO2. Conversely, post-LVRS PaCO2 bore no relationship to its pre-LVRS value, whereas changes in PaCO2 were tightly related ( r2 = 0.96) to variables, reflecting decrease in static lung hyperinflation (intrinsic positive end-expiratory pressure and residual volume/total lung capacity) and increase in airflow potential (tidal volume and maximal inspiratory pressure), but not to V̇a/Q̇ distribution changes. Individual gas exchange responses to LVRS vary greatly, but can be explained by changes in combinations of determining variables that are different for oxygen and carbon dioxide.

Portopulmonary hypertension (PoPH) is a serious condition without an established treatment. Drugs used to treat pulmonary hypertension may have detrimental effects on portal hypertension. This study was designed to assess in patients with PoPH the acute effects of inhaled iloprost (iILO) on pulmonary and hepatic hemodynamics and to evaluate the clinical outcome after 12 months of treatment. We conducted 2 separate studies. In the first one, 21 patients with PoPH were acutely tested with 2.8 microg of iILO. Pulmonary and hepatic hemodynamics were assessed at the baseline and through 60 minutes after iILO. In the second one, we retrospectively evaluated 12 patients treated with iILO (30 microg/day) for more than 1 year. The 6-minute walk distance (6MWD), functional class (FC), and echocardiogram were analyzed at the baseline and after 12 months of treatment. In the acute study, iILO rapidly reduced pulmonary artery pressure (PAP; -16% + or - 8%, P0.001) and pulmonary vascular resistance (-18% + or - 14%, P0.001). The cardiac output did not change initially but decreased after 30 minutes. The hepatic venous pressure gradient (HVPG) and hepatic blood flow did not vary through the study. Pulmonary vasodilation induced by iILO was inversely related to HVPG. In the long-term evaluation, iILO improved FC by 1 or more in 7 patients (P = 0.04) and increased 6MWD by 67 + or - 59 m at 12 months (P0.001). No change in systolic PAP was observed. Two patients died because of hepatic complications, and 4 additional patients presented clinically significant events that were related to hepatic disease in 2 and worsening of pulmonary hypertension in 2. We conclude that in patients with PoPH, iILO produces rapid and selective pulmonary vasodilation without altering the hepatic hemodynamics. Its long-term use may provide sustained improvements in symptoms and exercise tolerance in some patients with PoPH. A randomized, controlled trial is warranted to establish its clinical role in this serious condition.