[A new strategy to establish a hepatopulmonary syndrome model in rats by inducing abdominal compartment syndrome in the presence of cirrhosis].

ABSTRACT

OBJECTIVE: To find a practical method to establish hepatopulmonary syndrome (HPS) in rats for use as an experimental model system. METHODS: Forty male Sprague-Dawley rats were equally divided into a normal group (injected subcutaneously with 3 mL/kg of olive oil for 12 weeks), abdominal compartment syndrome (ACS) group (injected subcutaneously with 3 mL/kg olive oil for 12 weeks, followed by an intraperitoneal injection of 4% succinylated gelatin and maintenance of 20 mmHg abdominal pressure for 3 h), cirrhosis group (injected subcutaneously with 40% carbon tetrachloride (CCl4) in olive oil twice weekly for 12 weeks, with first dose doubled), and an ACS+ cirrhosis (HPS model) group (CCl4-induced, followed by the intraperitoneal injection with succinylated gelatin and 3 h of 20 mmHg abdominal pressure). The mice were sacrificed to perform blood gas analysis and to assess lung pathology. Comparisons between two groups were carried out by non-parametric analysis, and multiple comparisons were carried out by the Kruskal-Wallis H test. RESULTS: Blood gas analyses showed significant differences in the values of pH for the normal group (7.41+/-0.04), the ACS group (7.22+/-0.06), the cirrhosis group (7.53+/-0.04), and the HPS model group (7.47+/-0.02) (P less than 0.05). The ACS group and the HPS model group showed significantly different values of partial pressure of oxygen (PaO2; 58.57+/-5.41 and 58.20+/-3.19 mm Hg) and of alveolar-arterial oxygen difference (AaDO2; 83.86+/-28.49 and 84.80+/-11.82 mm Hg) than the normal group and the cirrhosis group (PaO2 86.67+/-1.37 and 85.00+/-2.53 mm Hg; AaDO2 38.17+/-9.20 and 37.00+/-6.23 mm Hg) (P less than 0.05). Pathological analysis of the lungs from the ACS group revealed widened alveolar septa, different-sized alveolar spaces, reduced lung capacity, edema and hemorrhage in some of the alveolar cavities, and telangiectasia in the alveolar walls. The lungs from the cirrhosis group also showed widened alveolar septa, different-sized alveolar spaces, and reduced lung capacity, but were distinct in the features of inflammatory cell infiltration, and hyperemia in the pulmonary vessels. The lungs from the HPS model group showed all of the features of both the lungs from the ACS and cirrhosis groups, but also showed macrophage accumulation and microthrombi in the pulmonary vessels. CONCLUSION: Inducing ACS in the setting of CCL4-induced cirrhosis in a rat generates pathological features that adequately mirror those of HPS and may represent a useful experimental model for in vivo studies of HPS.