Effect of β2-adrenergic receptor stimulation on lung fluid in stable heart failure patients

Introduction: The purpose of this study was to determine 1) if stable heart-failure patients with reduced ejection fraction (HFrEF) have elevated extravascular lung water (EVLW) versus healthy control subjects, and 2) the effect of acute β2AR agonist inhalation on lung fluid balance. Methods: Twenty-two stable HFrEF patients and 18 age- and sex-matched healthy subjects were studied. Lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary conductance (DmCO), pulmonary capillary blood volume (Vc) (via rebreathe) and lung tissue volume (Vtis) (via computed tomography) were assessed before and within 30 min of administration of nebulized albuterol. EVLW was derived as Vtis – Vc. Results: Pre-albuterol, Vtis and EVLW were greater in HFrEF vs. control (998 ± 200 vs. 884 ± 123 ml, P = 0.041; 943 ± 202 vs. 802 ± 133 ml, P = 0.015, respectively). Albuterol decreased Vtis and EVLW in HFrEF (−4.6 ± 7.8%, P = 0.010; −4.6 ± 8.8%, P = 0.018) and control (−2.8 ± 4.9%, P = 0.029; −3.0 ± 5.7%, P = 0.045). There was an inverse relationship between pre-albuterol values and the pre- to post-albuterol change for EVLW (r2 = −0.264, P = 0.015) and DmCO (r2 = −0.343, P = 0.004) in HFrEF only. Conclusion: Lung fluid is elevated in stable HFrEF patients relative to healthy subjects. Stimulation of the β2ARs may cause fluid removal in HFrEF, especially in patients who exhibit greater evidence for increased lung water at baseline

Modulation of epithelial sodium channel (ENaC) expression in mouse lung infected with Pseudomonas aeruginosa

BACKGROUND: The intratracheal instillation of Pseudomonas aeruginosa entrapped in agar beads in the mouse lung leads to chronic lung infection in susceptible mouse strains. As the infection generates a strong inflammatory response with some lung edema, we tested if it could modulate the expression of genes involved in lung liquid clearance, such as the α, β and γ subunits of the epithelial sodium channel (ENaC) and the catalytic subunit of Na(+)-K(+)-ATPase. METHODS: Pseudomonas aeruginosa entrapped in agar beads were instilled in the lung of resistant (BalB/c) and susceptible (DBA/2, C57BL/6 and A/J) mouse strains. The mRNA expression of ENaC and Na(+)-K(+)-ATPase subunits was tested in the lung by Northern blot following a 3 hours to 14 days infection. RESULTS: The infection of the different mouse strains evoked regulation of α and β ENaC mRNA. Following Pseudomonas instillation, the expression of αENaC mRNA decreased to a median of 43% on days 3 and 7 after infection and was still decreased to a median of 45% 14 days after infection (p < 0.05). The relative expression of βENaC mRNA was transiently increased to a median of 241%, 24 h post-infection before decreasing to a median of 43% and 54% of control on days 3 and 7 post-infection (p < 0.05). No significant modulation of γENaC mRNA was detected although the general pattern of expression of the subunit was similar to α and β subunits. No modulation of α(1)Na(+)-K(+)-ATPase mRNA, the catalytic subunit of the sodium pump, was recorded. The distinctive expression profiles of the three subunits were not different, between the susceptible and resistant mouse strains. CONCLUSIONS: These results show that Pseudomonas infection, by modulating ENaC subunit expression, could influence edema formation and clearance in infected lungs