Reduced pulmonary clearance of endothelin in congestive heart failure: a marker of secondary pulmonary hypertension.
BACKGROUND
Endothelin-1 (ET-1) levels are elevated in congestive heart failure (CHF) in relation with the severity of pulmonary hypertension. We evaluated whether a reduced pulmonary ET-1 clearance could contribute to this elevation.


RESULTS
We determined pulmonary ET-1 clearance in 24 patients with CHF in relation with hemodynamics, plasma ET-1, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Pulmonary ET-1 extraction, measured by the single bolus indicator-dilution technique, was reduced to 32 +/- 14% in comparison to historic controls (47 +/- 7%). Plasma ET-1 clearance by the lungs (924 +/- 588 mL/min) was also much lower than in controls (1424 +/- 79 mL/min). Clearance correlated inversely with mean pulmonary artery pressure (PAP, r = -.47, P = .017) and pulmonary capillary wedge pressure (r = -.47, P = .017) and positively with the rate of left ventricular (LV) relaxation LV -dP/dt (r = .593, P = .004). After multivariate analysis, only mean PAP and LV -dP/dt were independently correlated with ET-1 clearance (r = -.40, P = .03, and r = .55, P = .005, respectively). Plasma ET-1 levels did not correlate with clearance (r = .038, P = .86), and there was no significant arteriovenous ET-1 gradient. There was a mild nonsignificant correlation between plasma ET-1 and pulmonary artery systolic pressure (r = .38, P = .06), but a strong correlation with right atrial pressure (r = .696, P < .0001) and NT-proBNP levels (r = .51, P = .001), which were maintained after multivariate linear regression (r = .60, P = .001, and r = .32, P = .04, respectively).


CONCLUSIONS
Pulmonary ET-1 clearance is reduced in CHF in relation with the severity of pulmonary hypertension. This reduced clearance does not significantly modulate plasma ET-1 levels. Whether this is only a marker of secondary pulmonary hypertension or could modulate pulmonary vascular tone will require further studies.
Department of Medicine, Montreal Heart Institute, Quebec, Canada.
Cezar
C
Staniloae
Jocelyn
J
Dupuis
Michel
M
White
Gilbert
G
Gosselin
Ihor
I
Dyrda
Marc
M
Bois
Jacques
J
Crépeau
Raoul
R
Bonan
Alexandre
A
Caron
Joël
J
Lavoie
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D019332:Endothelin-1 / Q000097:blood / Q000378:metabolism*; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000209:etiology; D007201:Indicator Dilution Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000097:blood*; D010446:Peptide Fragments / Q000096:biosynthesis / Q000097:blood*; D011498:Protein Precursors / Q000096:biosynthesis / Q000097:blood*; D011652:Pulmonary Circulation; D011669:Pulmonary Wedge Pressure; D012044:Regression Analysis; D016276:Ventricular Function
D015415:Biomarkers; D019332:Endothelin-1; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011498:Protein Precursors; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain