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 heat (heat shock preconditioning) provides a cytoprotective effect on oxidative 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 of the liver, was investigated by using intravital fluorescence microscopy. In Sprague-Dawley rats, normothermic ischemia was induced by totally clamping the hepatoduodenal ligament for 20 min, followed by 120 min of reperfusion. 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 postischemic decrease in sinusoidal perfusion rate and sinusoidal diameter, and the postischemic increase in the number of stagnant leukocytes in sinusoids and adherent leukocytes in postsinusoidal venules were significantly attenuated in the heat shock-treated animals. Furthermore, liver enzyme release (glutamate pyruvate transaminase and alpha-glutathione S-transferase) was significantly reduced and postischemic deterioration of bile production was attenuated. The 7-day survival rate after 20-minute ischemia was significantly improved from 50% to 80% (heat shock-nontreated group vs. heat shock-treated group, P < 0.05). These results indicate that heat shock preconditioning attenuates ischemia/reperfusion-induced hepatic injury by preventing postischemic microvascular disturbances, and that its protective effect is circumstantially associated with the concomitant induction of heat shock protein 70.
Terajima
H
H
Institute for Surgical Research, Klinikum Grosshadern Ludwig-Maximilians University, Munich, Germany.
Kondo
T
T
Enders
G
G
Hammer
C
C
Thiery
J
J
Yamamoto
Y
Y
Yamaoka
Y
Y
Messmer
K
K
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism; D001794:Blood Pressure; D005982:Glutathione Transferase / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008833:Microcirculation; D008856:Microscopy, Fluorescence / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control; D015996:Survival Rate; D013696:Temperature
D018840:HSP70 Heat-Shock Proteins; D005982:Glutathione Transferase; D000410:Alanine Transaminase