ABSTRACT
Occlusion of the vascular inflow to the liver is a useful technique in liver surgery; unfortunately, it may influence postoperative liver regeneration. The purpose of this study is to evaluate the effect of hepatic blood inflow occlusion on liver regeneration following partial hepatectomy in normal and thioacetamide induced cirrhosis in a rat model, and to investigate the protective effect of trimetazidine. a known anti-ischemic drug on liver regeneration after hepatectomy with blood inflow occlusion. Sixty male Wistar rats were divided into two groups [30 rats in each, group I and II]. Rats in group [I] represented normal liver; those in group [II] represented a model of induced liver cirrhosis by intraperitoneal injection of thioacetamide, three times per week for 8 consecutive weeks. Animals of each group were subdivided into 2 subgroups [15 rats in each, subgroup Ia, Ib and Ia, IIb]. Animals of subgroups Ib and IIb were pretreated for 7 days before surgery with trimetazidine by intraperitoneal route. All animals were subjected to laparotomy with 30 minutes hepatic blood inflow occlusion, followed by approximately 65% hepatectorny. The rats were allocated to killing on days 1, 2, 7 posthepatectomy. Liver function tests [albumin, alanine amino-transferase [ALT] and bilirubini, percentage of liver weight and proliferating cell nuclear antigen [PCNA] labeling indices were assessed. The postoperative mortality rates were higher among rats with cirrhotic liver subjected to hepatectomy compared to control rats. There was no significant change in serum albumin and ALT between subgroup Ia. Ib with normal liver, however there was significant difference as regard serum albumin and ALT between cirrhotic subgroup IIa, IIb with improved results for subgroup IIb pretreated with trimetazidine. There was no significant difference in serum bilirubin between subgroup Ia and Ib and subgroup IIa and IIb. On comparing normal and cirrhutic rats, subgroup Ia and IIa and hb and IIb there was highly significant decrease of albumin level and highly significant increase in ALT and bilirubin levels in cirrhotic animals compared to control rats. There was significant improvement in hepatic regeneration measured by the percentage of liver weight at the time of killing and PCNA labeling indices between control rats, subgroup Ia and Ib and cirrhotic rats, subgroup IIa and IIb on days 1 and 2 with non-significant difference on day 7. Comparing the regenerative capacities of normal and cirrhotic liver, there was highly significant increase of proliferating cells in control rats and the regeneration of cirrhotic Iiver was delayed than normal liver. Hepatic blood inflow occlusion for thirty minutes before hepatectomy caused an injury in the remnant liver with significantly depressed regenerative capacity and consequent delayed recovery of liver function particularly in cirrhotic rats compared with normal controls. However, pretreatment with [rimetazidine alleviated ischemia-reperfusion injury during liver surgery resulting in improved liver regeneration, function and survival rate