Endothelin-1 across the lung circulation in patients with pulmonary arterial hypertension and influence of epoprostenol infusion.
BACKGROUND
The endothelin-1 (ET-1) system plays a pathophysiologic role in patients with pulmonary arterial hypertension (PAH). Results from previous studies assessing the transpulmonary gradient of ET-1 have been inconsistent. The influence of an intravenous epoprostenol infusion on the transpulmonary ET-1 gradient is unknown.


METHODS
In a prospective investigation, serum concentrations of ET-1 were measured in 39 consecutive patients (31 women; mean age, 20-77 years) with pulmonary hypertension (33 with PAH) and compared with 20 controls. The effect of intravenous epoprostenol administration on the transpulmonary gradient of ET-1 was analyzed in 13 patients with pulmonary hypertension. Blood samples were taken simultaneously from the pulmonary artery and radial artery.


RESULTS
The serum levels of ET-1 were significantly higher in the arterial (3.9 +/- 1.28 vs 2.53 +/- 0.24 pg/ml, p < 0.001) and mixed venous blood samples (3.9 +/- 1.21 vs 2.52 +/- 0.29 pg/ml, p < 0.001) in patients with pulmonary hypertension than in controls. The arterial/venous ratio of ET-1 in patients (1.0 +/- 0.1) and in the control group (1.0 +/- 0.05) was similar (p = 0.79). During intravenous epoprostenol infusion, there were no changes in the mean transpulmonary ET-1 gradient (0.98 +/- 0.07 vs 0.96 +/- 0.09, p = 0.52), despite significant hemodynamic changes.


CONCLUSIONS
The ET-1 radial artery/pulmonary artery ratio of unity indicates a balanced release and clearance of ET-1 across the lung circulation in controls and in patients with different forms of pulmonary hypertension. ET-1 levels across the pulmonary circulation did not change during epoprostenol infusion.
Selimovic
Nedim
N
Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden. nedim.selimovic@vgregion.se
Andersson
Bert
B
Bergh
Claes-Håkan
CH
Sakiniene
Egidija
E
Carlsten
Hans
H
Rundqvist
Bengt
B
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D019332:Endothelin-1 / Q000097:blood*; D011464:Epoprostenol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011651:Pulmonary Artery; D011652:Pulmonary Circulation; D017534:Radial Artery; D055815:Young Adult
D000959:Antihypertensive Agents; D019332:Endothelin-1; D011464:Epoprostenol