Implications of heat shock proteins during liver surgery and liver perfusion

Cells primed by sublethal stress transiently overproduce heat shock proteins (HSPs) and thereby develop tolerance to the next lethal stress. This response in organisms is called the stress response and involves the induction of HSPs. To assist the liver in developing tolerance for warm ischemia-reperfusion injury, which sometimes jeopardizes the patients after extended surgery for malignancies with vascular invasion in the liver, basic experiments to activate the stress response using stress preconditioning were performed. Heat shock preconditioning in rat livers has been shown to induce tolerance against warm ischemia-reperfusion injury in normal, fibrotic, and steatotic livers. Ischemic preconditioning using short-term Pringle's maneuver and pharmacological preconditioning using doxorubicin were also effective. In rats, heat shock preconditioning protected livers from free radical injury induced by the oral administration of carbon tetrachloride. The above data were supported by animal survival, suppression of serum transaminase levels, and improved energy status of the liver after intervention. Increased production of HSP72 was observed after preconditioning. In addition, the significance of HSP production as a stress parameter was demonstrated during the reperfusion of congested portal blood to the ischemic liver. The ill effect of congested portal blood could not be detected by conventional parameters but was detected by observing the increase in HSP72 production. Stress preconditioning seems to be a promising strategy to counter the damaging effect of hepatic warm ischemia during liver surgery and liver perfusion.