TY - JOUR
T1 - Serum oxidative/anti-oxidative stress balance is dysregulated in potentially pulmonary hypertensive patients with liver cirrhosis
T2 - A case control study
AU - Terao, Masako
AU - Takaki, Akinobu
AU - Maruyama, Takayuki
AU - Oe, Hiroki
AU - Yasunaka, Tetsuya
AU - Tamaki, Naofumi
AU - Nakamura, Kazufumi
AU - Tomofuji, Takaaki
AU - Yagi, Takahito
AU - Sadamori, Hiroshi
AU - Umeda, Yuzo
AU - Shinoura, Susumu
AU - Yoshida, Ryuichi
AU - Nouso, Kazuhiro
AU - Ekuni, Daisuke
AU - Koike, Kazuko
AU - Ikeda, Fusao
AU - Shiraha, Hidenori
AU - Morita, Manabu
AU - Ito, Hiroshi
AU - Fujiwara, Toshiyoshi
AU - Yamamoto, Kazuhide
N1 - Publisher Copyright:
© 2015 The Japanese Society of Internal Medicine.
PY - 2015/11/15
Y1 - 2015/11/15
N2 - Objective Hepatopulmonary syndrome (HPS) is characterized by vascular dilatation and hyperdynamic circulation, while portopulmonary hypertension (POPH) is characterized by vasoconstriction with fibrous obliteration of the vascular bed. Vasoactive molecules such as nitric oxide (NO) are candidate factors for cirrhotic complications associated with these diseases. However, oxidative stress balance is not well characterized in HPS and POPH. The present objective is to investigate the oxidative stress and anti-oxidative stress balance and NO pathway balance in patients with potential HPS and POPH. Methods We recruited patients with decompensated cirrhosis (n=69) admitted to our hospital as liver transplantation candidates. Patients exhibiting partial pressure of oxygen lower than 80 mmHg and alveolararterial oxygen gradient (AaDO2) ≥15 mmHg were categorized as potentially having HPS (23 of 69 patients). Patients exhibiting a tricuspid regurgitation pressure gradient ≥25 mmHg were categorized as potentially having POPH (29 of 61 patients). Serum reactive oxygen metabolites were measured and anti-oxidative OXYadsorbent test (OXY) were performed, and the balance of these tests was defined as the oxidative index. The correlation between these values and the clinical characteristics of the patients were assessed in a crosssectional study. Results Potential HPS patients exhibited no correlation with oxidative stress markers. Potential POPH patients exhibited lower OXY (p=0.037) and higher oxidative index values (p=0.001). Additionally, the vascular NO synthase enzyme inhibiting protein, asymmetric dimethylarginine, was higher in potential POPH patients (p=0.049). The potential POPH patients exhibited elevated AaDO2, suggesting the presence of pulmonary shunting. Conclusion Potential POPH patients exhibited elevated oxidative stress with decreased anti-oxidative function accompanied by inhibited NO production. Anti-oxidants represent a candidate treatment for potential POPH patients.
AB - Objective Hepatopulmonary syndrome (HPS) is characterized by vascular dilatation and hyperdynamic circulation, while portopulmonary hypertension (POPH) is characterized by vasoconstriction with fibrous obliteration of the vascular bed. Vasoactive molecules such as nitric oxide (NO) are candidate factors for cirrhotic complications associated with these diseases. However, oxidative stress balance is not well characterized in HPS and POPH. The present objective is to investigate the oxidative stress and anti-oxidative stress balance and NO pathway balance in patients with potential HPS and POPH. Methods We recruited patients with decompensated cirrhosis (n=69) admitted to our hospital as liver transplantation candidates. Patients exhibiting partial pressure of oxygen lower than 80 mmHg and alveolararterial oxygen gradient (AaDO2) ≥15 mmHg were categorized as potentially having HPS (23 of 69 patients). Patients exhibiting a tricuspid regurgitation pressure gradient ≥25 mmHg were categorized as potentially having POPH (29 of 61 patients). Serum reactive oxygen metabolites were measured and anti-oxidative OXYadsorbent test (OXY) were performed, and the balance of these tests was defined as the oxidative index. The correlation between these values and the clinical characteristics of the patients were assessed in a crosssectional study. Results Potential HPS patients exhibited no correlation with oxidative stress markers. Potential POPH patients exhibited lower OXY (p=0.037) and higher oxidative index values (p=0.001). Additionally, the vascular NO synthase enzyme inhibiting protein, asymmetric dimethylarginine, was higher in potential POPH patients (p=0.049). The potential POPH patients exhibited elevated AaDO2, suggesting the presence of pulmonary shunting. Conclusion Potential POPH patients exhibited elevated oxidative stress with decreased anti-oxidative function accompanied by inhibited NO production. Anti-oxidants represent a candidate treatment for potential POPH patients.
KW - Hepatopulmonary syndrome
KW - Liver cirrhosis
KW - Oxidative stress
KW - Portopulmonary syndrome
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U2 - 10.2169/internalmedicine.54.4889
DO - 10.2169/internalmedicine.54.4889
M3 - Article
C2 - 26567993
AN - SCOPUS:84947125016
SN - 0918-2918
VL - 54
SP - 2815
EP - 2826
JO - Internal Medicine
JF - Internal Medicine
IS - 22
ER -