Endothelin-1 and asymmetric dimethylarginine in children with left-to-right shunt after intracardiac repair.
BACKGROUND
Endothelin-1 (ET-1) is an endogenous vasoconstrictive peptide hormone and asymmetric dimethylarginine (ADMA) acts as an endogenous inhibitor of nitric oxide synthase. We hypothesized that both could contribute to pulmonary hypertension in patients with left-to-right shunt after intracardiac repair.


METHODS
We prospectively analyzed ET-1 and ADMA plasma levels in 31 patients (m = 16; f = 15) at an age of 0.6 [0.2-27] years (median [range]) with left-to-right shunt (ASD II: n = 12; VSD: n = 11; AVSD: n = 8) presenting with a Qp/Qs of 2.7 [1.4-6.3] and a pulmonary arterial mean pressure (PAP) of 23 [13-57] mmHg. Blood specimens were taken prior to cardiopulmonary bypass (CPB), after weaning from CPB and at 3, 6, 12 and 24 h after CPB.


RESULTS
12/31 patients were found to have pulmonary hypertension prior to intracardiac repair and 11/12 patients showed persistent pulmonary hypertension during the first 24 h after CPB. Patients with pulmonary hypertension at 12 h after CPB showed significant higher plasma ET-1 compared with patients with normal PAP (1.4 [0-7.9] versus 0.5 [0-2.5] pg/ml; P = 0.048 (Mann-Whitney)). Plasma ADMA decreased from 1.3 [0.75-2.3] micromol/l before CPB to 0.7 [0.4-2.1] micromol/l at 12 h (P < 0.05). However patients with pulmonary hypertension did not show different ADMA plasma levels.


CONCLUSIONS
Increased plasma ET-1 but not inhibition of nitric oxide synthase by ADMA is associated with pulmonary hypertension after intracardiac repair.
Loukanov
Tsvetomir
T
Dept. of Cardiac Surgery, University Medical Center, University of Heidelberg, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany.
Arnold
Raoul
R
Gross
Jasmin
J
Sebening
Christian
C
Klimpel
Homa
H
Eichhorn
Joachim
J
Hoss
Katharina
K
Ulmer
Herbert E
HE
Kark
Matthias
M
Gorenflo
Matthias
M
D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002315:Cardiopulmonary Bypass; D002648:Child; D002675:Child, Preschool; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood*; D007223:Infant; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000097:blood; D000073718:Pancreatitis-Associated Proteins; D011183:Postoperative Complications / Q000097:blood*; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D019332:Endothelin-1; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase