Effects of ischemic pre- and postconditioning on HIF-1α, VEGF and TGF-β expression after warm ischemia and reperfusion in the rat liver

28 rats were randomized into five groups: control; ischemia/reperfusion; ischemic preconditioning (IPC); ischemic postconditioning (IPO); combined IPC and IPO. IPC consisted of 10 min of ischemia and 10 min of reperfusion. IPO consisted of three cycles of 30 sec. reperfusion and 30 sec. of ischemia.HIF-1α mRNA expression was significantly increased after liver ischemia compared to controls (p = 0.010). HIF-1α mRNA expression was significantly lower in groups subjected to IPC or combined IPC and IPO when compared to the ischemia/reperfusion group (p = 0.002). VEGF-A mRNA expression increased in the ischemia/reperfusion or combined IPC and IPO groups when compared to the control group (p < 0.05).Ischemic conditioning seems to prevent HIF-1α mRNA induction in the rat liver after ischemia and reperfusion. This suggests that the protective effects of ischemic conditioning do not involve the HIF-1 system. On the other hand, the magnitude of the HIF-1α response might be a marker for the degree of I/R injuries after liver ischemia. Further studies are needed to clarify this issue.Colorectal cancer is a leading form of cancer in the Western world. Approximately 50% of patients with this disease have, or will eventually develop, liver metastases. Surgical removal of those metastases remains the treatment of choice, with a five year survival rate of 37%-58% after resection [1-3]. Major hemorrhage and blood transfusion during liver resection is related to an increase in morbidity and mortality [4-6]. Vascular clamping is a frequently used method for reducing blood loss [7]. Several studies have shown that the normal livers tolerate periods of continuous warm ischemia up to 90 min and intermittent warm ischemia up to 120 min [8-10].However, ischemia/reperfusion (I/R) injury of the liver is an unfortunate side effect of this method, ranging from slightly elevated liver enzymes to acute liver failure [11]. Ischemic pre- or postconditioning (IPC or IPO), defined as brief periods of