Systemic Oxidative Stress and Endothelial Dysfunction is Associated With an Attenuated Acute Vascular Response to Inhaled Prostanoid in Pulmonary Artery Hypertension Patients

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• 作者：Luigi A. Gabrielli MD¹ ; Pablo F. Castro MD¹ ;   ; ^{pcastro@med.puc.cl} ; Ivan Godoy MD¹ ; Rosemarie Mellado PhD² ; Robert C. Bourge MD³ ; Hernan Alcaino MSc⁴ ; Mario Chiong PhD⁵ ; Douglas Greig MD¹ ; Hugo E. Verdejo MD¹ ;   ; ⁵ ; Mario Navarro MSc⁵ ; Rafael Lopez MSc⁵ ; Barbra Toro MSc⁵ ; Clara Quiroga PhD⁵ ; Guillermo Dí ; az-Araya PhD⁵ ; Sergio Lavandero PhD⁵ ;   ; ⁶ ;   ; ⁷ ; Lorena Garcia PhD⁵ ;   ; ^{logarcia@uchile.cl}
• 关键词：Pulmonary hypertension ; endothelial function ; oxidative stress ; endothelial superoxide dismutase
• 刊名：Journal of Cardiac Failure
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：17
• 期：12
• 页码：1012-1017
• 全文大小：214 K

文摘

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 ¡À 0.6 vs. 10.7 ¡À 0.6 % , P < .01), increased MDA levels and XO activity (0.6 ¡À 0.2 vs. 0.3 ¡À 0.2 ¦ÌM, P < .01 and 0.04 ¡À 0.01 vs. 0.03 ¡À 0.01 U/mL, P?= .02, respectively) and decreased eSOD activity (235 ¡À 23 vs. 461 ¡À 33 AUC, P < .01). Iloprost improved right cardiac output (3.7 ¡À 0.6 to 4.1 ¡À 1.2 L/min, P?= .02) and decreased pulmonary vascular resistance (4.1 ¡À 1.1 to 2.9 ¡À 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.