Decrease by ACE-inhibition of the excessive alveolar-capillary membrane resistance to gas transfer in chronic heart failure.
In this study the mechanisms were investigated whereby ACE-inhibitors improve pulmonary diffusion for carbon monoxide (DLco) in chronic heart failure. The two subcomponents of DLco are the alveolar-capillary membrane conductance (DM) and the capillary blood volume (VC). Stress failure of the membrane in chronic heart failure provides a mechanism for reduction of DM and, as a consequence, impairment of DLco. In 27 patients with chronic heart failure in NYHA functional class II to III and in 13 age- and sex-matched normal subjects, we evaluated the pulmonary function and determined DM and VC, according to the classic Roughton and Forster method, while they were given placebo, at 48 hours and 8 weeks after starting enalapril treatment (10 mg bid). ACE-inhibition had no effect in controls at both short- and mid-term. In chronic heart failure patients, a reduction in VC (likely consequence of a decrease in capillary pulmonary pressure) was the only change observed at 48 hours. At 8 weeks, DM was greatly increased even when the effective alveolar volume (VA) was accounted for (DM/VA), resulting in a significant improvement in DLco, despite a decrease in VC. The slow onset DM improvement makes it likely that the modulatory effect of ACE-inhibition on the membrane function emerges gradually, suggesting that it is likely dissociated from changes in pulmonary capillary pressure and VC. Thus, derangements of the alveolar-capillary membrane in chronic heart failure increase gas diffusion resistance; ACE-inhibition restores the diffusive properties of the membrane and gas transfer, and protects the lung when the heart is failing.
Istituto di Cardiologia, Università degli Studi, Milano.
M
M
Guazzi
P
P
Agostoni
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015824:Blood-Air Barrier / Q000502:physiology*; D002200:Capillary Resistance; D002908:Chronic Disease; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008168:Lung / Q000502:physiology* / Q000503:physiopathology; D012129:Respiratory Function Tests; D014109:Total Lung Capacity
D000806:Angiotensin-Converting Enzyme Inhibitors