Serum Oxidative/anti-oxidative Stress Balance Is Dysregulated in Potentially Pulmonary Hypertensive Patients with Liver Cirrhosis: A Case Control Study
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- Terao Masako
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan Department of Internal Medicine, Fukuyama City Hospital, Japan
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- Takaki Akinobu
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Maruyama Takayuki
- Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Oe Hiroki
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Yasunaka Tetsuya
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Tamaki Naofumi
- Department of Preventive Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan
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- Nakamura Kazufumi
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Tomofuji Takaaki
- Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Yagi Takahito
- Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Sadamori Hiroshi
- Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Umeda Yuzo
- Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Shinoura Susumu
- Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Yoshida Ryuichi
- Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Nouso Kazuhiro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Ekuni Daisuke
- Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Koike Kazuko
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Ikeda Fusao
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Shiraha Hidenori
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Morita Manabu
- Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Ito Hiroshi
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Fujiwara Toshiyoshi
- Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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- Yamamoto Kazuhide
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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Abstract
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.<br> 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 alveolar-arterial 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 OXY-adsorbent 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 cross-sectional study.<br> 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.<br> 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.<br>
Journal
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- Internal Medicine
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Internal Medicine 54 (22), 2815-2826, 2015
The Japanese Society of Internal Medicine