Multiple pathogenic factor-induced complications of cirrhosis in rats: A new model of hepatopulmonary syndrome with intestinal endotoxemia

Abstract

AIM:To develop and characterize a practical model of Hepatopulmonary syndrome (HPS) in rats. METHODS:The experimental animals were randomized into five feeding groups: (1) control (fed standard diet), (2) control plus intraperitoneal injection with lipopolysaccharide (LPS), (3) cirrhosis (fed a diet of maize flour, lard, cholesterol, and alcohol plus subcutaneously injection with carbon tetrachloride (CCl4) oil solution), (4) cirrhosis plus LPS, and (5) cirrhosis plus glycine and LPS. The blood, liver and lung tissues of rats were sampled for analysis and characterization. Technetium 99m-labeled macroaggregated albumin (Tc99m-MAA) was used to test the dilatation of pulmonary microvasculature. RESULTS:Typical cirrhosis and subsequent hepatopulmonary syndrome was observed in the cirrhosis groups after an 8 wk feeding period. In rats with cirrhosis, there were a decreased PaO2 and PaCO2 in arterial blood, markedly decreased arterial O2 content, a significantly increased alveolar to arterial oxygen gradient, an increased number of bacterial translocated within mesenteric lymph node, a significant higher level of LPS and tumor necrosis factor-α (TNF-α) in plasma, and a significant greater ratio of Tc99m-MAA brain-overlung radioactivity. After LPS administration in rats with cirrhosis, various pathological parameters got worse and pulmonary edema formed. The predisposition of glycine antagonized the effects of LPS and significantly alleviated various pathological alterations. CONCLUSION:The results suggest that: (1) a characteristic rat model of HPS can be non-invasively induced by multiple pathogenic factors including high fat diet, alcohol, cholesterol and CCl4; (2) this model can be used for study of hepatopulmonary syndrome and is clinically relevant; and (3) intestinal endotoxemia (IETM) and its accompanying cytokines, such as TNF-α, exert a crucial role in the pathogenesis of HPS in this model.

The indices of endogenous intoxication in rats with different models of hepatopulmonary syndrome

“…Cholesterol was appended at 0.5% of feeding for the whole experiment. Alcohol was used in the drinking water exclusively (300 mL/L) during the whole experiment 15 .…”

Expression of the 78 kD glucose-regulated protein is induced by endoplasmic reticulum stress in the development of hepatopulmonary syndrome

“…Liver cirrhosis and HPS were induced in these animals as described in our previously published study (Su et al 2010; Zhang et al 2007): rats in the HPS group were fed with a mixture of maize flour, 0.5% cholesterol, and 20% lard (lard used only for the first 2 wk), and they only drank 5%–15% (v/v) ethanol. These animals received subcutaneous injection of carbon tetrachloride (CCl 4 ) solution (0.5 ml/100 g bodyweight) on the first day of experiment and thereafter the CCl 4 solution was injected (0.3 ml/100 g bodyweight) at an interval of three days.…”

Levertransplantasjon i stedet for lungetransplantasjon

“…Økt NO-produksjon i lungekretsløpet kan muligens forklares ved økte konsentrasjoner av endotoksin i blodet fordi en sviktende lever ikke nøytraliserer intestinalt endotoksin pga. portalsystemisk shunting i lever og/eller fordi redusert retikuloendotelial cellefunksjon i lever er redusert ved cirrhose (5 …”