Heat shock pretreatment protects pulmonary isografts from subsequent ischemia-reperfusion injury

Background: Heat shock has been associated with the acquisition of toleranc e to a wide variety of stressful conditions, including ischemia. This is pa rtly mediated by the production of various heat shock proteins (HSP), inclu ding HSP70. One novel approach to the reduction of ischemia-reperfusion inj ury after lung transplantation is the induction of HSP70 by heat pretreatme nt of the donor. The purpose of this study was to investigate the feasibili ty of this approach in an animal model of lung transplantation. Methods: Animals were divided into six main groups, with groups I to III re presenting transplanted animals: In groups I and II, donor animals were ane sthetized and then underwent heat stress 6 and 12 hours before organ harves t, respectively. Control animals underwent general anesthesia but no heat s tress. After harvest, left lungs from groups I to III were preserved for 18 hours at 4 degrees C and then implanted into isogeneic recipients, which w ere killed 24 hours after reperfusion to assess graft function. Group IV an d V animals underwent heat stress followed by a recovery period of 6 and 12 hours, respectively. Lungs were collected both at the time of harvest (rig ht lungs) and after 18 hours of cold preservation (left lungs). Group VI se rved as nontransplanted controls. Groups TV to VI did not undergo lung tran splantation. Results: At the time of harvest but before implantation, HSP70 was signific antly increased in heat-shocked nontransplanted donor lungs (groups IV and V) compared with group VI controls. After 18 hours of cold preservation, HS P70 levels were higher in group IV compared with group V and group VI contr ols. At 24 hours after reperfusion, mean arterial oxygenation was significa ntly higher in group I compared with group II and group III controls (290.2 5 +/- 24.5 vs 154.5 +/- 23.9 and 119.6 +/- 11.3 mm Hg, respectively; P <.00 1). Myeloperoxidase activity was improved in group I compared with group II I controls (0.048 +/- 0.018 vs 0.137 +/- 0.036 Delta OD/mg/min, respectivel y; P <.05). The wet/dry weight ratio was also improved in group I compared with group III controls (6.2 +/- 0.3 vs. 7.8 +/- 0.4, respectively; P <.05) , Conclusions: Heat pretreatment of the donor 6 hours before harvest results in increased synthesis of HSP70, which offers a dramatic protective effect against subsequent ischemia-reperfusion injury in the lung isograft.