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AIM: To explore a simple, effective, safe and operable pretreatment for conferring tolerance against ischemiareperfusion (I-R) injury in rat livers.METHODS: Forty-five rats were divided into five groups (each group n = 9). Group C: control group; group G:geranylgeranylacetone (GGA) was administered without heat stress; group 5: local heat stress alone; group WG:GGA plus whole-body heat stress; group SG: GGA administration plus local heat stress. After completion of the I-R procedure, the ischemic-reperfused liver lobes in five groups were resected and tested for heat shock protein (HSP70) by RT-PCR, West blotting analysis and immunohistochemical staining. The blood samples were collected for ALT and AST measurement at the end of occlusion of blood supply, 30 min after reperfusion, 24,48, 72 h after surgery from the inferior vena cava. Survival was monitored for 1 wk.RESULTS: The production of HSP70 after I-R injury increased, the liver enzyme levels after reperfusion decreased rapidly, and the survival rates increased in groups C-SG.CONCLUSION: The combination of GGA plus local somatothermal stimulation is a simple, effective, safe and operable pretreatment to induce HSP70 in patients with liver tumor and cirrhosis before hepatectomy and in donors before harvesting graft for liver transplantation.