[Acetylsalicylic acid antagonism vs ACE inhibitor in congestive heart failure as shown by a diminished respiratory and exercise capacity].
Our hypothesis is that regulation of the lung vessel tone and microvascular permeability may be disrupted in chronic heart failure (CHF) and angiotensin converting enzyme (ACE) inhibition may contribute to their readjustment. This hypothesis is based on the fact that KII-ACE, the same enzyme that converts angiotensin I and inactivates bradykinin, is highly concentrated in the luminal surface of the lung vessels and its blockade in CHF may reduce their exposure to an excess of angiotensin II and augment the action of prostaglandins and nitric oxide (NO) deriving from local kinin hyperconcentration. We probed whether ACE-inhibitors influence the pulmonary function; this is peculiar of CHF; they act as KII- or ACE-blockers. Aspirin was utilized as a prostaglandin synthesis inhibitor. We investigated 16 CHF patients and 16 age- and sex-matched normal volunteers or mild untreated hypertensives. All were non-smokers, not taking ACE-inhibitors, aspirin or other cyclooxygenase inhibitors. Pulmonary function tests, exercise testing with respiratory gases and echocardiography were performed in the run-in and repeated at the end of placebo, enalapril (10 mg t.i.d.), enalapril plus aspirin (325 mg/day) and aspirin given in random order and double-blind fashion for 15 days each. Enalapril, as compared to placebo, caused an increase in mean voluntary ventilation (MVV) and alveolar-capillary diffusing capacity for carbon monoxide (DLCO) in CHF, that were counteracted by the addition of aspirin. Aspirin alone was not effective. Enalapril and aspirin were ineffective on the pulmonary function of controls. As to the functional capacity, enalapril increased exercise tolerance time, oxygen consumption (VO2p), minute ventilation (VEp) tidal volume (VTp) and reduced the ratio of volume of dead space gas (VDp) to VTp (VD/VTp), at peak exercise in CHF patients. These effects all were inhibited by the combination of aspirin and were not observed in controls. In CHF VO2p changes from placebo correlated with those in DLCO (r = 0.80, p < 0.0001) and not with those in ejection fraction. This correlation was abolished by aspirin and was not seen in controls. Variations in VD/VTp in CHF patients while on enalapril were related to those in DLCO (r = -0.69, p = 0.003). In CHF the ventilatory equivalent for carbon dioxide production per minute at 1 liter was diminished with enalapril and not in combination with aspirin. Derangements related to CHF are the substrate for benefits of ACE-inhibition on pulmonary function and exercise capacity. Pulmonary diffusion limitation is an important mediator of exercise impairment and its improvement with enalapril goes in parallel with VD/VT, MVV, VT, VE to VCO2 relationship and not with ejection fraction. These patterns reflect changes occurring within the lung that are not related to left ventricular function. The counteracting influence of aspirin on these affects bespeaks a substantial participation of prostaglandins that might readjust capillary permeability and lung interstitial fluid content or alveolar capillary membrane diffusing capacity.
Guazzi
M
M
Istituto di Cardiologia, Università degli Studi, Milano.
Lauri
G
G
Melzi
G
G
Cattadori
G
G
Agostoni
P
P
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000627:therapeutic use*; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006334:Heart Function Tests / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D012119:Respiration / Q000187:drug effects*; D012129:Respiratory Function Tests / Q000706:statistics & numerical data
D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D004656:Enalapril; D001241:Aspirin
Antagonismo di acido acetilsalicilico vs ACE-inibitore nell'insufficienza cardiaca congestizia rivelato da una diminuita capacità respiratoria e di esercizio.