FK506 with Portal Decompression Exerts Beneficial Effects following Extended Hepatectomy in Dogs

Abstract

The present study was designed to elucidate the effectiveness of portal decompression and FK506 (FK) pretreatment in extended hepatectomy in dogs. In the first set of experiment the effect of portal decompression was evaluated in two groups of dogs which underwent extended hepatectomies (80%) with or without (control) a side-to-side portacaval shunt. The presence of the shunt significantly (p < 0.05) improved the 7-day survival of the animals (57.1%) when compared with those of the control group (28.6%) and eventually the portal pressure was significantly lower and mean arterial pressure was significantly higher in the shunt group (p < 0.05). Moreover, the animals with lower portal pressure (≤220 mm of saline) had a significantly improved 7-day survival rate than those with higher portal pressure (p < 0.001). To evaluate the role of FK pretreatment in extended hepatectomy, a more severe model of 90% hepatectomy was used in four different groups: portacaval shunt, shunt and FK pretreatment, FK pretreatment, and hepatectomy only (control). Although the shunt improved the survival rate in the 80% hepatectomy model, neither shunt (8.3%) nor FK pretreatment (0%) independently improved the survival of the animals when the hepatectomy was extended to 90%. FK pretreatment significantly improved the survival (33.3%, p < 0.05) and hepatic functions of the animals only in the presence of a shunt. Also hepatic microcirculation measured with a laser Doppler flowmeter was significantly better in the remnant liver of all treated groups than in the control group (p < 0.01). In conclusion, extended hepatectomy (90%) could be performed in otherwise normal liver after FK pretreatment and a side-to-side portacaval shunt, which improve the regenerative response in a stable hemodynamic animal.