TY - JOUR
T1 - Systemic oxidative stress and endothelial dysfunction is associated with an attenuated acute vascular response to inhaled prostanoid in pulmonary artery hypertension patients
AU - Gabrielli, Luigi A.
AU - Castro, Pablo F.
AU - Godoy, Ivan
AU - Mellado, Rosemarie
AU - Bourge, Robert C.
AU - Alcaino, Hernan
AU - Chiong, Mario
AU - Greig, Douglas
AU - Verdejo, Hugo E.
AU - Navarro, Mario
AU - Lopez, Rafael
AU - Toro, Barbra
AU - Quiroga, Clara
AU - Díaz-Araya, Guillermo
AU - Lavandero, Sergio
AU - Garcia, Lorena
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/12/1
Y1 - 2011/12/1
N2 - Background: Systemic endothelial dysfunction and increased oxidative stress have been observed in pulmonary arterial hypertension (PAH). We evaluate whether oxidative stress and endothelial dysfunction are associated with acute pulmonary vascular bed response to an inhaled prostanoid in PAH patients. Methods: Fourteen idiopathic PAH patients and 14 controls were included. Oxidative stress was assessed through plasma malondialdehyde (MDA) levels and xanthine oxidase (XO) and endothelial-bound superoxide dismutase (eSOD) activity. Brachial artery endothelial-dependent flow-mediated vasodilation (FMD) was used to evaluate endothelial function. Hemodynamic response to inhaled iloprost was assessed with transthoracic echocardiography. Results: PAH patients showed impaired FMD (2.8 ± 0.6 vs. 10.7 ± 0.6%, P <.01), increased MDA levels and XO activity (0.6 ± 0.2 vs. 0.3 ± 0.2 μM, P <.01 and 0.04 ± 0.01 vs. 0.03 ± 0.01 U/mL, P =.02, respectively) and decreased eSOD activity (235 ± 23 vs. 461 ± 33 AUC, P <.01). Iloprost improved right cardiac output (3.7 ± 0.6 to 4.1 ± 1.2 L/min, P =.02) and decreased pulmonary vascular resistance (4.1 ± 1.1 to 2.9 ± 0.9 Wood U, P =.01). Changes in right cardiac output after prostanoid inhalation correlated significantly with baseline eSOD activity and FMD (Rho: 0.61, P <.01 and Rho: 0.63, P =.01, respectively). Conclusion: PAH patients show increased systemic oxidative stress and endothelial dysfunction markers. Response to inhaled prostanoid is inversely related to both parameters.
AB - Background: Systemic endothelial dysfunction and increased oxidative stress have been observed in pulmonary arterial hypertension (PAH). We evaluate whether oxidative stress and endothelial dysfunction are associated with acute pulmonary vascular bed response to an inhaled prostanoid in PAH patients. Methods: Fourteen idiopathic PAH patients and 14 controls were included. Oxidative stress was assessed through plasma malondialdehyde (MDA) levels and xanthine oxidase (XO) and endothelial-bound superoxide dismutase (eSOD) activity. Brachial artery endothelial-dependent flow-mediated vasodilation (FMD) was used to evaluate endothelial function. Hemodynamic response to inhaled iloprost was assessed with transthoracic echocardiography. Results: PAH patients showed impaired FMD (2.8 ± 0.6 vs. 10.7 ± 0.6%, P <.01), increased MDA levels and XO activity (0.6 ± 0.2 vs. 0.3 ± 0.2 μM, P <.01 and 0.04 ± 0.01 vs. 0.03 ± 0.01 U/mL, P =.02, respectively) and decreased eSOD activity (235 ± 23 vs. 461 ± 33 AUC, P <.01). Iloprost improved right cardiac output (3.7 ± 0.6 to 4.1 ± 1.2 L/min, P =.02) and decreased pulmonary vascular resistance (4.1 ± 1.1 to 2.9 ± 0.9 Wood U, P =.01). Changes in right cardiac output after prostanoid inhalation correlated significantly with baseline eSOD activity and FMD (Rho: 0.61, P <.01 and Rho: 0.63, P =.01, respectively). Conclusion: PAH patients show increased systemic oxidative stress and endothelial dysfunction markers. Response to inhaled prostanoid is inversely related to both parameters.
KW - endothelial function
KW - endothelial superoxide dismutase
KW - oxidative stress
KW - Pulmonary hypertension
UR - http://www.scopus.com/inward/record.url?scp=84855979023&partnerID=8YFLogxK
U2 - 10.1016/j.cardfail.2011.08.008
DO - 10.1016/j.cardfail.2011.08.008
M3 - Article
C2 - 22123364
AN - SCOPUS:84855979023
SN - 1071-9164
VL - 17
SP - 1012
EP - 1017
JO - Journal of Cardiac Failure
JF - Journal of Cardiac Failure
IS - 12
ER -