Glucocorticoid pretreatment protects cardiac function and induces cardiac heat shock protein 72.
Acute administration of glucocortiocoids reduces inflammation. Increasing knowledge of the mechanisms of action indicate that pretreatment with glucocorticoids could have organ-protective effects. We investigated whether pretreatment 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). Rats were given vehicle or MP-40 mg/kg im as a double injection starting either 24 or 120 h (5 days) before their hearts were excised for Langendorff perfusion (n = 6-11 hearts in each group). MP improved left ventricular function and coronary flow during reperfusion after 30 min of global ischemia and reduced infarct size. Cardiac HSP72 gradually increased in a 24-h time course after MP treatment, and the increase was sustained 5 days afterward (immunoblotting). HSP72 mRNA was either reduced or unchanged, indicating a posttranscriptional regulation. Pretreatment with hydrocortisone or dexamethasone (n = 7-8 hearts of each) similarily increased cardiac HSP72 24 h afterward. This paper demonstrates that glucocorticoids increase cardiac HSP72 and protect organ function against ischemia-reperfusion injury.
Crafoord Laboratory of Experimental Surgery, Karolinska Hospital, S-171 76 Stockholm, Sweden. Guro.Valen@cmm.ki.se
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G
Valen
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Kawakami
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Tähepôld
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Dumitrescu
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Löwbeer
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Vaage
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003402:Creatine Kinase / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005938:Glucocorticoids; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D003907:Dexamethasone; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D006854:Hydrocortisone; D008775:Methylprednisolone