Glucocorticoid pretreatment protects cardiac function and induces cardiac heat shock protein 72

Acute administration of glucocortiocoids reduces inflammation. Increasing k nowledge of the mechanisms of action indicate that pretreatment with glucoc orticoids could have organ-protective effects. We investigated whether pret reatment with methylprednisolone (MP) protected the heart against ischemia- reperfusion dysfunction, and we hypothetized that this protection might be due to induction of the cardioprotective heat shock protein 72 (HSP72). Rat s were given vehicle or MP-40 mg/kg im as a double injection starting eithe r 24 or 120 h (5 days) before their hearts were excised for Langendorff per fusion (n = 6-11 hearts in each group). MP improved left ventricular functi on and coronary flow during reperfusion after 30 min of global ischemia and reduced infarct size. Cardiac HSP72 gradually increased in a 24-h time cou rse after MP treatment, and the increase was sustained 5 days afterward (im munoblotting). HSP72 mRNA was either reduced or unchanged, indicating a pos ttranscriptional regulation. Pretreatment with hydrocortisone or dexamethas one (n = 7-8 hearts of each) similarily increased cardiac HSP72 24 h afterw ard. This paper demonstrates that glucocorticoids increase cardiac HSP72 an d protect organ function against ischemia-reperfusion injury.