Plasma adrenomedullin and endothelin-1 concentration during low-dose dobutamine infusion: Relationship between pulmonary uptake and pulmonary vascular pressure/flow characteristics.
OBJECTIVE
To study the role of endothelin (ET-1) and adrenomedullin (AM) on pulmonary vascular pressure/flow characteristic (pulmonary arterial pressure/cardiac output (Pap/CO)) during low-dose dobutamine infusion.


METHODS
Case control study of 14 patients (12 men, 2 women) with severe lung disease (chronic obstructive pulmonary disease, COPD n=5; cystic fibrosis, CF n=9) and 5 control subjects (CTRL, 4 men, 1 woman). ET-1 and AM plasma levels in pulmonary artery (mixed venous blood, ven) and aorta or femoral artery (arterial, art), were measured at baseline and during dobutamine infusion (5-10-15 mcg kg(-1) min(-1)). The Ppa/CO coordinates obtained at baseline and during dobutamina infusion for each patients were used to calculate the Slope and Intercept by linear regression analysis.


RESULTS
Baseline hemodynamics measurements were similar in the three groups with a trend towards a mild elevation in Ppa in CF group (Ppa mm Hg: CTRL 19+/-3.5, COPD 19.4+/-5.5, CF 22.7+/-7.5). Baseline plasma ET-1(ET-1ven pg ml(-1): CTRL 13.9+/-6.7, COPD 20.1+/-14, CF 20.4+/-7.1; ET-1art pg ml(-1): CTRL 16.7+/-6.4, COPD 20.1+/-11.7, CF 18.1+/-3.9) and AM (AMven pg ml(-1): CTRL 15.8+/-5, COPD 31.8+/-17.6, CF 27.7+/-7.6; AMart pg ml(-1): CTRL 15.9+/-1.4, COPD 21.4+/-3.8, CF 27+/-7.6) showed a trend towards higher value among patients' groups compared to the controls. Baseline ET-1 pulmonary gradient did not show significant difference among the three groups as well AM pulmonary gradient. Dobutamine infusion caused a comparable increase of heart rate and CO in the three groups. Mean pulmonary pressure had a trend towards a greater increase in COPD and CF than in controls, consequently, pulmonary Pap/CO relationship showed a steeper slope in patients' groups (Slope mm Hg L(-1) min(-1): CTRL 0.9+/-0.3, COPD 2.1+/-0.8 p<0.02 vs. CTRL, CF 1.9+/-0.9 p<0.03 vs CTRL). During dobutamine plasma ET-1 and AM showed a great individual variability resulting in no significant difference among groups. ET-1 pulmonary gradient showed a trend towards pulmonary uptake in patients' groups (ET-1art-ven pg min(-1): CTRL 2.7+/-2.9, COPD-6.1+/-7.8, CF -4+/-4.8) while AM pulmonary gradient did not show any particular pattern. During dobutamine ET-1 was significantly correlated to Pap/CO characteristics (Slope and ET-1ven, r=-0.59, p<0.05; Slope and ET-1art-ven, r=-0.60, p<0.05; Intercept and ET-1art-ven, r=0.63, p<0.004), and ET-1art-ven was the only independent variable related to Slope and Intercept.


CONCLUSIONS
In patients with moderate pulmonary vascular impairment, ET-1 pulmonary gradient, but not AM pulmonary gradient, is inversely correlated with pulmonary incremental resistance, suggesting a role of ET-1 in the regulation of pulmonary vascular resistance.
Vizza
Carmine Dario
CD
Department of Cardiovascular and Respiratory Sciences, University La Sapienza, Rome, Italy.
Letizia
Claudio
C
Badagliacca
Roberto
R
Sciomer
Susanna
S
Poscia
Roberto
R
Della Rocca
Giorgio
G
Iacoboni
Carlo
C
Leonardo
De Luca
de L
Quattrucci
Serena
S
Dario
Cotesta
C
Luigi
Petramala
P
Fedele
Francesco
F
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D053607:Adrenomedullin / Q000097:blood* / Q000378:metabolism; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D004280:Dobutamine / Q000008:administration & dosage* / Q000378:metabolism; D019332:Endothelin-1 / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008171:Lung Diseases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010455:Peptides / Q000097:blood; D011652:Pulmonary Circulation / Q000187:drug effects*; D012129:Respiratory Function Tests
D000318:Adrenergic beta-Agonists; D019332:Endothelin-1; D010455:Peptides; D053607:Adrenomedullin; D004280:Dobutamine