Reduction of hepatic microcirculatory failure caused by normothermic ischemia/reperfusion-induced injury by means of heat shock preconditioning

Transient sublethal hyperthermia and the recovery from this exposure to hea t (heat shock preconditioning) provides a cytoprotective effect on oxidativ e insults through an intracellular protective response, heat shock response . The impact of heat shock preconditioning on hepatic microvascular failure , which is a causative determinant of ischemia/reperfusion-induced injury o f the liver, was investigated by using intravital fluorescence microscopy. In Sprague-Dawley rats, normothermic ischemia was induced by totally clampi ng the hepatoduodenal ligament for 20 min, followed by 120 min of reperfusi on. Heat shock preconditioning was performed by whole-body hyperthermia (42 degrees C for 15 min) and subsequent 48 h recovery. In accordance with the prominent induction of heat shock protein 70 in the liver tissue, the post ischemic decrease in sinusoidal perfusion rate and sinusoidal diameter, and the postischemic increase in the number of stagnant leukocytes in sinusoid s and adherent leukocytes in postsinusoidal venules were significantly atte nuated in the heat shock-treated animals. Furthermore, liver enzyme release (glutamate pyruvate transaminase and cc-glutathione S-transferase) was sig nificantly reduced and postischemic deterioration of bile production was at tenuated. The 7-day survival rate after 20-minute ischemia was significantl y improved from 50% to 80% (heat shock-nontreated group vs. heat shock-trea ted group, P < 0.05). These results indicate that heat shock preconditionin g attenuates ischemia/reperfusion-induced hepatic injury by preventing post ischemic microvascular disturbances, and that its protective effect is circ umstantially associated with the concomitant induction of heat shock protei n 70.