From the Department of Medicine, Montreal Heart Institute, Montreal,
Quebec, Canada.
Correspondence to Dr Jocelyn Dupuis, Department of Medicine, Montreal Heart Institute, Research Center, 5000 Belanger St E, Montreal, Quebec, Canada, H1T 1C8. E-mail dupuisj{at}icm.umontreal.ca
Background—The pulmonary
vascular bed is a major site for endothelin-1 (ET-1) clearance. A
reduced clearance could contribute to the increase in circulating ET-1
levels found in heart failure (HF). We therefore evaluated the effect
of HF on pulmonary ET-1 clearance and on plasma ET-1
concentrations.
Methods and Results—Rats with myocardial infarction (n=24) were
compared with sham-operated rats (n=22). The lungs were isolated and
perfused at a constant flow rate of 10 mL/min. Pulmonary ET-1
clearance was measured by the single-bolus indicator-dilution technique
with 125I-labeled ET-1. Infarct rats developed HF with mild
pulmonary hypertension. ET-1 extraction was reduced by HF from
63±1.5% to 41±4.5% (mean±SEM, P<0.001). Mixed
venous (MV) and aortic ET-1 levels doubled with HF. There was a plasma
ET-1 gradient across the lungs of sham rats (MV-aortic levels,
0.21±0.12 pg/mL) but not in lungs of HF rats (0.01±0.17 pg/mL).
Plasma ET-1 levels correlated closely and inversely with ET-1
extraction (P<0.001).
Conclusions—HF is associated with reduced pulmonary ET-1
clearance that contributes to the increase in circulating levels.
© 1998 American Heart Association, Inc.
Basic Science Reports
Reduced Pulmonary Clearance of Endothelin-1 Contributes to the Increase of Circulating Levels in Heart Failure Secondary to Myocardial Infarction
Key Words: endothelin • heart failure • pulmonary heart disease • myocardial infarction • lung
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