HEAT-SHOCK-PROTEIN-70 MESSENGER-RNA REFLECTS THE SEVERITY OF ISCHEMIAHYPOXIA-REPERFUSION INJURY IN THE PERFUSED-RAT-LIVER/

Objectives: To determine whether ischemia-reperfusion and hypoxia-reox ygenation cause cellular damages and stress responses in an isolated p erfused rat liver model. To determine whether the increased synthesis of stress protein messenger RNA reflects cellular injury. Design: Pros pective, controlled study. Setting: Institutional laboratories. Subjec ts: Male Sprague-Dawley rats. Interventions: Isolated rat livers with cell free perfusion were exposed to various periods of ischemia-reperf usion or hypoxia-reoxygenation. Measurements and Main Results: We meas ured hepatic oxygen consumption and alanine aminotransferase leakage f rom liver during perfusion. We analyzed the gene expression of heat sh ock protein 70, a major stress protein, of the liver by Northern blott ing after perfusion. The expression of heat shock protein 70 messenger RNA augmented as the reperfusion period increased. The expression lev el after graded ischemia or hypoxia significantly correlated with the calculated hepatic oxygen debt (r(2) =.737; p < .001; n = 21), or with the accumulated alanine aminotransferase leakage from the liver (r(2) =.509; p <.001; n = 21). Conclusions: These results suggest that the accumulation of heat shock protein 70 messenger RNA reflects the sever ity of ischemia-reperfusion and hypoxia-reoxygenation injuries, and th at a stress response in reperfusion can be triggered without formed el ements of blood.