title: Hepatopulmonary syndrome: the role of intra-abdominal hypertension and a novel mouse model.
abstract: OBJECTIVE
  Hepatopulmonary syndrome (HPS) is considered as a triad of chronic liver disease, pulmonary vascular ectasia and severe hypoxemia. The study aims to investigate the pathological mechanism of intra-abdominal pressure (IAP) in HPS and establish a novel mouse model.
  
  
  METHODS
  Fifty male ICR mice were randomly divided into experimental and control group, receiving subcutaneous injection of carbon tetrachloride and water, respectively. Mice in experimental group were then divided into 4 sub-groups with the intraperitoneal injection of different volume of albumin to form different IAP (0, 5, 10 and 20 cmH2O). All the mice were then sacrificed 24 hours later and blood gas analysis was conducted. In addition, liver and lung histopathology was also examined.
  
  
  RESULTS
  Blood gas analysis in different IAP suggested the respiratory alkalosis. Arterial partial pressure of oxygen significantly decreased in the IAP=10 cmH2O (68.13 ± 3.56, P<0.01) and 20 cmH2O (66.00 ± 3.78, P<0.01). Alveolar-arterial oxygen pressure difference increased markedly in the IAP=10 cmH2O (54.60 ± 6.80, P<0.001) and 20 cmH2O (57.04 ± 5.60, P<0.001). According to lung histopathology, macrophages were found to accumulate in the alveolar spaces and the widened alveolar walls were detected. In addition, there was visible blood stasis in the alveolar walls and numerous red blood cells extravasated into air space in the IAP=10 and 20 cmH2O.
  
  
  CONCLUSIONS
  Our study suggested that intra-abdominal hypertension was a significant pathological mechanism of HPS. Meanwhile, we have established a novel mouse model that will now be optimized with further investigation of the mechanism and therapeutic targets of HPS.
authors.affiliation: Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Zhaojie
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Qi
authors.affiliation: Division of Hepatobiliary Surgery, 302 Hospital of Chinese People's Liberation Army Beijing 100039, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Xu
authors.affiliation: Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Shenglan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Yizhong
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Wanrong
authors.initials: W
authors.lastname: Ma
authors.affiliation: Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Mingxin
authors.initials: M
authors.lastname: Xu
authors.affiliation: Division of Gastroenterology and Hepatology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Yang
mesh_terms: D000418:Albumins; D000472:Alkalosis, Respiratory / Q000097:blood / Q000209:etiology; D000818:Animals; D001784:Blood Gas Analysis; D002251:Carbon Tetrachloride; D020065:Hepatopulmonary Syndrome / Q000097:blood / Q000209:etiology* / Q000473:pathology; D059325:Intra-Abdominal Hypertension / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D000418:Albumins; D002251:Carbon Tetrachloride; D010100:Oxygen
keywords: Hepatopulmonary syndrome; abdominal compartment syndrome; animal model; intra-abdominal hypertension