| Improvement of alveolar-capillary membrane diffusing capacity with enalapril in chronic heart failure and counteracting effect of aspirin. | |
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MedLine Citation:
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PMID: 9107182 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 (VO2), and exercise tolerance and reduced the ratio of dead space to tidal volume (VD/VT) and the ventilatory equivalent for carbon dioxide production (VE/VCO2). On enalapril, VO2 (r = .80, P < .0001) and VD/VT (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 VE/VCO2; amelioration in VO2 and VD/VT 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. |
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Authors:
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M Guazzi; G Marenzi; M Alimento; M Contini; P Agostoni |
Publication Detail:
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Type: Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Circulation Volume: 95 ISSN: 0009-7322 ISO Abbreviation: Circulation Publication Date: 1997 Apr |
Date Detail:
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Created Date: 1997-05-13 Completed Date: 1997-05-13 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1930-6 Citation Subset: AIM; IM |
Affiliation:
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Istituto di Cardiologia dell'Università degli Studi, Consiglio Nazionale delle Ricerche, Fondazione "Monzino," I.R.C.C.S., Milan, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Angiotensin-Converting Enzyme Inhibitors / pharmacology*, therapeutic use Aspirin / pharmacology* Blood-Air Barrier / drug effects* Bradykinin / physiology Cyclooxygenase Inhibitors / pharmacology* Diffusion Double-Blind Method Enalapril / antagonists & inhibitors, pharmacology*, therapeutic use Epoprostenol / physiology Exercise Test Female Heart Failure / complications, drug therapy*, metabolism, physiopathology Humans Hydralazine / pharmacology Hypertension / drug therapy, physiopathology Isosorbide Dinitrate / pharmacology Male Middle Aged Peptidyl-Dipeptidase A / physiology Pulmonary Alveoli / blood supply, drug effects*, enzymology Pulmonary Circulation / drug effects* Pulmonary Gas Exchange / drug effects* Respiratory Function Tests |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin-Converting Enzyme Inhibitors; 0/Cyclooxygenase Inhibitors; 35121-78-9/Epoprostenol; 50-78-2/Aspirin; 58-82-2/Bradykinin; 75847-73-3/Enalapril; 86-54-4/Hydralazine; 87-33-2/Isosorbide Dinitrate; EC 3.4.15.1/Peptidyl-Dipeptidase A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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