MICROTROMBOSI SINUSOIDALE EPATICA INDOTTA DAL LIPOPOLISACCARIDE: RUOLO PROTETTIVO DELLA SIMVASTATINA IN UN MODELLO MURINO DI ENDOTOSSIEMIA

Background:Liver dysfunction is one of the earliest high-risk markers for multi-organ failure (MOF) in patients with sepsis. In a recent study, using a murine model, we demonstrated that lipopolysaccharide (LPS) injection provokes hepatic microvascular dysfunction, associated with marked endothelitis in perisinusoidal areas. Furthermore, endothelial dysfunction drives vascular derangement and organ failure associated with sepsis. However, the consequences of sepsis on liver sinusoidal endothelial function are unknown. Statins might improve microvascular dysfunction in sepsis. The present study explores liver vascular abnormalities and the effects of statins in a rat model of endotoxemia. Methods: For this purpose, lipopolysaccharide (LPS) or saline was given to: (1) rats treated with placebo; (2) rats treated with simvastatin (25 mg/kg, orally), given at 3 and 23 hours after LPS/saline challenge; (3) rats treated with simvastatin (25 mg/kg/24 h, orally) from 3 days before LPS/saline injection. Liver microvascular function was assessed by molecular studies and liver function tests. Results: At 24 h, LPS induced liver endothelial dysfunction, as shown by a decreased of thrombomodulin and a increase of fibrin. Treatment with simvastatin from 3 days before LPS prevented the increase of fibrin. Conclusions: LPS administration induces intrahepatic endothelial dysfunction that might be prevented by simvastatin, suggesting that statins might have potential for liver protection during endotoxemia.