Plasma adrenomedullin and endothelin-1 concentration during low-dose dobutamine infusion: Relationship between pulmonary uptake and pulmonary vascular pressure/flow characteristics

Aim: 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 min 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, CIF 20.4 +/- 7.1; ET-1art pg ml(-1): CTRL 16.7 +/- 6.4, COPD 20.1 +/- 11.7, CIF 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, CIF 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 min 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 +/- 12.9, 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-lven, r=-0.59,p < 0.05; Slope and ET-lartven, r=-0.60, p < 0.05; Intercept and ET-lart-ven, r=0.63, p < 0.004), and ET-lart-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. (c) 2006 Elsevier B.V. All rights reserved.