Beneficial effect of pentoxifylline on microvesicular steatotic livers submitted to a prolonged cold ischemia

The deleterious effect of steatosis on transplanted livers is mainly related to a microcirculation impairment. We investigated the effect of preservation duration on the recovery of isolated perfused rat steatotic livers and tested the effect of pentoxifylline (PTX), known to have a beneficial effect on hepatic microcirculation.

Fatty rat livers were obtained using a diet able to induce an 80% to 100% microvesicular steatosis within 7 days. We studied the effect of the duration of preservation (12 hr, 18 hr, and 24 hr) on fatty and normal isolated perfused rat liver. PTX was added to University of Wisconsin solution during cold storage (30 mM/kg of weight) and at reperfusion (3 mM) (n=5 livers in each group). Lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, bile production, and vascular resistance were evaluated. The liver injury at the end of perfusion was assessed by optical and electron microscopy.

For a 24-hr preservation period, fatty livers demonstrated increased enzymatic release (aspartate aminotransferase: 42+/-16 vs. 17+/-5 IU/L/g of liver, P<0.005; alanine aminotransferase: 32+/-13 vs. 13+/-3 IU/L/g of liver, P<0.005; lactate dehydrogenase: 1,207+/-497 vs. 291+/-195 IU/L/g of liver, P<0.001). Vascular resistance (0.32 vs. 0.15 cm H(2)O/min/mL, P<0.0005) and bile output (67+/-24 vs. 141+/-61 mg/g of liver, P<0.05) were decreased. Peliosis appeared after an 18-hr preservation period for fatty livers compared with a 24-hr preservation period for controls. All these negative effects were suppressed by PTX.

Diffuse microvesicular steatosis became deleterious only after long preservation times (24 hr). PTX prevented this effect.