Lipocortin-1 preserves myocardial responsiveness to beta-adrenergic stimulation in rat papillary muscle

1. During septic shock, myocardial contractile dysfunction is accompanied b y 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 papilla ry muscle for 15 h with endotoxin (lipopolysaccharide, LPS) and interferon- gamma (IFN-gamma). 3. Both baseline contractile function and inotropic responsiveness to isopr enaline 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 fu nction induced by LPS plus IFN-gamma. 5. The mechanisms of this protective action need to be explored further, bu t LC-1 may prove to be a novel cardioprotective agent for the management of septic shock.