IMPROVEMENT OF ALVEOLAR-CAPILLARY MEMBRANE DIFFUSING-CAPACITY WITH ENALAPRIL IN CHRONIC HEART-FAILURE AND COUNTERACTING EFFECT OF ASPIRIN

Background KII ACE, the enzyme that converts angiotensin I and inactiv ates bradykinin, is highly concentrated in the lungs; its blockade red uces exposure to angiotensin II and enhances expo sure to prostaglandi ns generated by local kinin hyperconcentration. Our hypothesis is that ACE inhibitors Improve pulmonary function in chronic heart failure (C HF) by readjusting lung vessel tone and permeability or alveolar-capil lary membrane diffusion. Methods and Results In 16 CHF patients and 16 normal volunteers or mild untreated hypertensives, pulmonary function and exercise tests with respiratory gas analysis were assessed on pla cebo, enalapril (10 mg BID), enalapril plus aspirin (325 mg/d), or asp irin, in random order and double blind, for 15 days each. In CHF, enal april increased pulmonary carbon monoxide diffusion (DLCO), oxygen con sumption (V) over dot O-2), and exercise tolerance and reduced the rat io of dead space to tidal volume (VD/VT) and the ventilatory equivalen t for carbon dioxide production ((V) over dot E/(V) over dot CO2). On enalapril (V) over dot O-2 (r=.80, P<.0001) and VD/VT (r=-.69, P=.003) changes from placebo correlated with those in DLCO. These effects wer e inhibited by aspirin and were absent in control subjects. In 8 addit ional patients, hydralazine-isosorbide dinitrate, as an alternative tr eatment for reducing pulmonary capillary wedge pressure (PCWP) and inc reasing exercise capacity, were more effective than enalapril for the PCWP but did not affect DLCO and (V) over dot E/(V) over dot CO2; amel ioration in (V) over dot O-2 and VD/VT was unrelated to DLCO and was n ot modified by aspirin. Conclusions ACE inhibition improved pulmonary diffusion in CHF. Hydralazine-isosorbide dinitrate failed to provide t his result. Counteraction by aspirin, a prostaglandin inhibitor, bespe aks prostaglandin participation while on enalapril that might readjust capillary permeability or alveolar-capillary membrane diffusion.