The Sinusoidal Pressure During Ischemia-Reperfusion Injury in Perfused Mouse Liver Pretreated With or Without l -NAME

Background Hepatic ischemia-reperfusion (I/R) is accompanied by liver weight gain and ascites formation possibly caused by an increase in the sinusoidal pressure, a determinant of hepatic transvascular fluid movement. However, changes in the sinusoidal pressure during hepatic I/R in mice are not known. It is also controversial whether nitric oxide (NO) exerts a beneficial or detrimental effect on hepatic I/R injury. We determined the changes in hepatic sinusoidal pressure and liver weight, and the effect of a NO synthase inhibitor, NG -nitro- l -arginine methyl ester ( l -NAME) on I/R injury of isolated mouse liver. Materials and methods Isolated liver from 20 male outbred ddY mice was perfused portally with diluted blood (Hct 3%). After pretreatment with l -NAME (100 μ m ) or d -NAME (100 μ m ), ischemia was induced at room temperature by occlusion of the inflow line of the portal vein for 1 h followed by 1-h reperfusion in a recirculating manner. The sinusoidal pressure was assessed by the double vascular occlusion pressure (Pdo), and pre- and postsinusoidal resistance was determined. Liver injury was assessed by blood levels of alanine aminotransferase (ALT). Results In the d -NAME group ( n = 7), immediately after reperfusion, the portal pressure increased by 2.8 ± 0.1 (SE) mmHg, which was accompanied by an increase in Pdo of 1.5 ± 0.1 mmHg, indicating increases in pre- and postsinusoidal resistance to a similar degree. Then, presinusoidal, but not postsinusoidal, resistance sustained increased until 60 min after reperfusion. Liver weight increased to 0.14 ± 0.04 g/g liver after reperfusion, followed by a gradual return to baseline. Blood ALT levels increased at 60 min after reperfusion. There were no significant differences in changes in the variables between the d - and l -NAME ( n = 7) groups. In the time-matched non- I/R control group ( n = 6), no changes in variables were observed for 2 h. Conclusions Mouse hepatic I/R causes marginal liver weight gain associated with a small and transient increase in the sinusoidal pressure, and nitric oxide does not play any significant roles in this injury.