Improvement of Alveolar–Capillary Membrane Diffusing Capacity With Enalapril in Chronic Heart Failure and Counteracting Effect of Aspirin

Abstract

Background KII ACE, the enzyme that converts angiotensin I and inactivates bradykinin, is highly concentrated in the lungs; its blockade reduces exposure to angiotensin II and enhances exposure to prostaglandins generated by local kinin hyperconcentration. Our hypothesis is that ACE inhibitors improve pulmonary function in chronic heart failure (CHF) by readjusting lung vessel tone and permeability or alveolar–capillary 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 placebo, enalapril (10 mg BID), enalapril plus aspirin (325 mg/d), or aspirin, in random order and double blind, for 15 days each. In CHF, enalapril increased pulmonary carbon monoxide diffusion (DLCO), oxygen consumption (V̇ o 2 ), and exercise tolerance and reduced the ratio of dead space to tidal volume (V d /V t ) and the ventilatory equivalent for carbon dioxide production V̇ e /V̇ co 2 ). On enalapril, V̇ o 2 ( r =.80, P <.0001) and V d /V t ( r =−.69, P =.003) changes from placebo correlated with those in DLCO. These effects were inhibited by aspirin and were absent in control subjects. In 8 additional patients, hydralazine–isosorbide dinitrate, as an alternative treatment for reducing pulmonary capillary wedge pressure (PCWP) and increasing exercise capacity, were more effective than enalapril for the PCWP but did not affect DLCO and V̇ e /V̇ co 2 ; amelioration in V̇ o 2 and V d /V t was unrelated to DLCO and was not modified by aspirin. Conclusions ACE inhibition improved pulmonary diffusion in CHF. Hydralazine–isosorbide dinitrate failed to provide this result. Counteraction by aspirin, a prostaglandin inhibitor, bespeaks prostaglandin participation while on enalapril that might readjust capillary permeability or alveolar–capillary membrane diffusion.