METABOLIC CHANGES IN A MODEL OF WARM LIVER ISCHEMIA/REPERFUSION INJURY IN RATS

Abstract

Background: Liver ischemia/reperfusion (IR) is characterized by tissue injury associated with metabolic derangements as occurs in Liver transplantation (LT) and hepatic surgery. We hypothesized that a model reproducing whole liver ischemia may allow studying with more accuracy the metabolic derangements that follows particular clinical scenarios like LT. Methods: Eighteen Wistar rats were divided into 3 groups of 6 animals: I) Control: normal rats not subjected to liver resection or IR; II) sham: rats submitted to resection of right and caudate liver lobes; III) Ischemia (IR): rats subjected to 60 min of partial warm liver ischemia of the left lateral and median lobes, followed by resection of non-ischemic lobes at beginning of reperfusion. Four hours after reperfusion rats were anesthetized and submitted to mechanical ventilation. The carotid artery was cannulated and arterial blood was collected for analysis of lactate, potassium, glucose, hemoglobin and liver transaminases. Then animals were killed by exsanguination. Results: The mean weigh of the rats was 229 ± 18 g. AST and ALT were increased in the IR group (6.675 ± 1.687 and 5.793 ± 1.119 U/L) compared to the sham (897 ± 304 and 815 ± 433 U/L) and control groups (99 ± 28 and 64 ± 27 U/L), P< 0.05. Glucose was decreased in the IR group (115 ± 30 mg/dl) compared to the sham (224 ± 101 mg/dL) and control (298 ± 115 mg/dl) groups, P< 0.05. Lactate was increased in the IR group (24.7 ± 10.2 mg/dl) compared to the sham group (14.8 ± 6.3 mg/dL), P< 0.05. There were no differences in potassium and hemoglobin between groups. However the potassium in the IR group tended to be higher than control and sham groups. Conclusions: This experimental model of warm liver I/R showed that after 60 min of ischemia the hepatic metabolism is reduced. There was a decrease of 40% in the glucose and an increase of 60% in lactate serum levels. This impairment of these metabolic variables was associated with an increase in liver transaminases indicating a correlation with the I/R injury. This model may be useful to study the metabolic hepatic disorders that accompanies liver ischemia/reperfusion.