Plasma beta-endorphin and adenosine concentration in pulmonary hypertension.

To determine whether beta-endorphin plays a role in the regulation of pulmonary vascular tone in patients with pulmonary hypertension, we investigated the relations between hemodynamics and beta-endorphin and adenosine concentrations in 3 clinical situations: (1) normal hemodynamics (7 subjects, mean pulmonary artery [PA] pressure 18.5 +/- 1 mm Hg); (2) moderate pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD) (8 patients, mean PA pressure 31 +/- 3 mm Hg); and (3) severe primary pulmonary hypertension (PPH) (8 patients, mean PA pressure 70 +/-5 mm Hg). Plasma beta-endorphin and adenosine were measured in a distal PA and in the femoral artery in room air and during oxygen inhalation. Beta-endorphin levels were similar in the pulmonary and systemic circulations. No difference was observed between patients with COPD and PPH, but relative to controls, both had significantly higher beta-endorphin levels. Pulmonary adenosine was significantly lower in patients with pulmonary hypertension than in controls (-60% in COPD [p <0.005] and -70% in PPH [p <0.001]). Pure oxygen administration significantly decreased adenosine and beta-endorphin levels, much more so in patients with COPD and PPH. We found a negative correlation between beta-endorphin and adenosine concentrations (r = -0.751, p <0.001): the higher the adenosine, the lower the beta-endorphin level. These observations suggest that because adenosine release by pulmonary vascular endothelium is reduced in pulmonary hypertension, the resulting worsened hypoperfusion and tissue oxygenation may cause increased beta-endorphin release.

Adenosine plasma concentration in pulmonary hypertension.

OBJECTIVE: In this study, we sought to appreciate the role of adenosine in the regulation of pulmonary vascular tone, especially in the case of clinical pulmonary hypertension, by investigating the relationship between endogenous plasma adenosine levels and pulmonary artery vasoconstriction. METHODS: Adenosine plasma concentrations, were measured simultaneously in the distal right pulmonary artery and in the femoral artery, both at steady state (room air) and during pure oxygen inhalation. Three clinical situations were considered: (1) normal hemodynamics [7 control subjects, mean pulmonary artery pressure (MPAP) = 18.5 +/- 1 mm Hg], (2) moderate pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD), (8 patients, MPAP = 31 +/- 3 mm Hg), (3) severe primary pulmonary hypertension (PPH), (8 patients, MPAP = 70 +/- 5 mm Hg). RESULTS: In every instance, adenosine evaluated by HPLC was higher in the pulmonary than in the systemic circulation. For room air, adenosine plasma concentrations were significantly lower in COPD (0.49 +/- 0.16 mumol l-1) and PPH patients (0.45 +/- 0.14 mumol l-1) than in controls (1.26 +/- 0.12 mumol l-1). During O2 administration, adenosine plasma concentrations all decreased but more so in COPD and PPH patients. The significant correlations between adenosine plasma concentrations and both pulmonary vascular resistance and PvO2, in controls, were not found in COPD or PPH patients. CONCLUSION: The adenosine plasma concentrations in the pulmonary circulation of PPH and COPD patients are low, and may contribute to pulmonary artery hypertension.

Hemodynamic effects of bilevel nasal positive airway pressure ventilation in patients with heart failure.

AIMS: Benefits of nasal continuous positive airway pressure (CPAP) in patients presenting with chronic heart failure (CHF) are controversial. The purpose of this study was to compare the hemodynamic effects of CPAP and bilevel positive airway pressure (BiPAP) in patients with or without CHF. METHODS AND RESULTS: Twenty patients with CHF and 7 with normal left ventricular function underwent cardiac catheterization. Measurements were made before and after three 20-min periods of BiPAP: expiratory positive airway pressure (EPAP) = 8 cm H2O and inspiratory positive airway pressure (IPAP) = 12 cm H2O, EPAP = 10 cm H2O and IPAP = 15 cm H2O, and CPAP = EPAP = IPAP = 10 cm H2O administered in random order. Positive pressure ventilation decreased cardiac output (CO) and stroke volume. No change was observed in either pulmonary or systemic arterial pressure. There was no difference in the hemodynamic effects of the three ventilation settings. Only mean pulmonary wedge pressure (MPWP) and heart rate were lower with CPAP than with BiPAP. CO decreased only in patients with low MPWP (

Effect of almitrine bismesylate on pulmonary vasoreactivity to hypoxia in chronic obstructive pulmonary disease.

The aim of this double-blind, placebo-controlled study was to determine whether acute administration of almitrine enhances hypoxic pulmonary vasoconstriction in patients with chronic obstructive pulmonary disease (COPD). Haemodynamics and blood gases were studied at various inspiratory fractional concentrations of oxygen (FIO2): 0.15, 0.21, 0.30 and 1.0, randomly administered for 20 min periods under constant infusion of either placebo or almitrine (8 micrograms.kg-1.min-1) in 20 patients with COPD. The almitrine group exhibited a significant increase in mean pulmonary artery pressure, pulmonary vascular resistance and arterial oxygen tension (PaO2) at FIO2 0.15, 0.21 and 0.30. During hypoxia, the increase in mean pulmonary pressure and pulmonary vascular resistance was three times greater in the almitrine group than the placebo group. No significant difference in cardiac output and systemic haemodynamics was found. These results suggest that almitrine at the dose used, enhances pulmonary vasoconstriction in COPD patients.

Long-term treatment of chronic obstructive lung disease by Nifedipine: an 18-month haemodynamic study.

This long-term controlled study was undertaken to assess the haemodynamic effects of chronic administration of Nifedipine (N). Twenty patients suffering from pulmonary hypertension secondary to chronic obstructive lung disease were divided into two groups. One group (treatment group) was instructed to take 30 mg of N daily and the other (control group) did not take N. Haemodynamic measurements were recorded before and after an 18-month observation period. For patients in the treatment group, Nifedipine was stopped 24 h prior to the second investigation. Acute response to a single dose of Nifedipine (10 mg sublingually) was also evaluated in all patients during the first and second investigations in order to estimate a possible tachyphylaxis. No significant modification in heart rate, mean pulmonary pressure, mean arterial pressure or blood gases was observed. Conversely, a 10% decrease in cardiac output (p less than 0.05) occurred in the control group. Pulmonary vascular response to acute administration of Nifedipine was the same in both groups before and after the observation period. These results suggest that while long-term administration of Nifedipine to patients with chronic obstructive lung disease does not improve pulmonary pressure, it may prevent a decrease in cardiac output. No tachyphylaxis was noted.