Lipocortin-1 preserves myocardial responsiveness to beta-adrenergic stimulation in rat papillary muscle.
1. During septic shock, myocardial contractile dysfunction is accompanied by the release of cytokines and enhanced production of nitric oxide, and the contractile dysfunction is prevented by glucocorticoids. 2. Myocardial dysfunction was induced in vitro by incubation of rat papillary muscle for 15 h with endotoxin (lipopolysaccharide, LPS) and interferon-gamma (IFN-gamma). 3. Both baseline contractile function and inotropic responsiveness to isoprenaline were markedly reduced by the combination of LPS plus IFN-gamma. 4. Lipocortin-1 (LC-1) is induced by glucocorticoids, and LC-1(2-26), its N-terminal fragment, protected the papillary muscle inotropic responsiveness to isoprenaline, but did not affect the decline in baseline contractile function induced by LPS plus IFN-gamma. 5. The mechanisms of this protective action need to be explored further, but LC-1 may prove to be a novel cardioprotective agent for the management of septic shock.
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Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D017305:Annexin A1 / Q000494:pharmacology*; D066298:In Vitro Techniques; D007371:Interferon-gamma; D007545:Isoproterenol / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000503:physiopathology; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides; D051381:Rats; D017207:Rats, Sprague-Dawley; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000503:physiopathology*
D000318:Adrenergic beta-Agonists; D017305:Annexin A1; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D010455:Peptides; C096153:annexin A1 peptide (2-26); D007371:Interferon-gamma; D007545:Isoproterenol