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.

Hyperperfusion Syndrome in Small-for-Size Livers

“…In this context, it was reported that the presence of a porto-systemic (portocaval) shunt effectively diminished portal venous pressure resulting in increased survival rates in animal studies [7][8][9] . However, as portal venous blood originates from the lienal and mesenteric veins, we investigated whether simultaneous splenectomy during extended partial hepatectomy might also positively infl uence postoperative smallfor-size syndrome, and thereby postoperative recovery.…”

“…These animals experienced lower AST levels (421 8 36 vs. 574 8 73 U/l) Beside size matching in the transplant situation [6] , other strategies have been described to reduce portal blood fl ow and to overcome postoperative portal hyperperfusion in small-for-size livers following extended liver resection. In this context, it was reported that the presence of a portosystemic (portocaval) shunt effectively diminished portal venous pressure resulting in increased survival rates in animal studies [7][8][9] .…”

90% Hepatectomy with a Porto-hepatic Shunt in a Canine Model: A Feasibility Study

“…Among these, the most important risk factor for liver failure after a major hepatectomy is remnant liver volume (Shirabe et al 1999). High portal and hepatic artery flow to small liver remnants leads to portal congestion, which damages remaining hepatic parenchyma (Bogetti et al 2004;Man et al 2003;Mitsumoto et al 1999). Additionally, increased portal pressure can lead to congestion and edema of the bowel wall, allowing translocation of bacteria and thereby increasing postoperative morbidity and mortality (Mitsumoto et al 1999).…”

“…High portal and hepatic artery flow to small liver remnants leads to portal congestion, which damages remaining hepatic parenchyma (Bogetti et al 2004;Man et al 2003;Mitsumoto et al 1999). Additionally, increased portal pressure can lead to congestion and edema of the bowel wall, allowing translocation of bacteria and thereby increasing postoperative morbidity and mortality (Mitsumoto et al 1999). The abrupt regenerative response of a small remnant liver (Ninomiya et al 2010) could exacerbate these problems, further increasing the risk of liver failure.…”

“…Mitsumoto and coworkers reported significantly improved 7-day survival in canines that underwent 80% hepatectomy with a side-to-side porto-caval shunt that lowered portal venous pressure (Mitsumoto et al 1999). However, when 90% hepatectomy removed all liver except the caudate lobe, no canines survived even with the porto-caval shunt (Mitsumoto et al 1999).…”