naloxone and Myocarditis

Little is known about effects of naloxone, an opiate receptor antagonist, upon experimental autoimmune myocarditis (EAM) in mice. The aim of the present study was to test the effects of naloxone upon EAM in mice. Four-week-old C57BL/6 mice were injected with porcine cardiac myosin. Naloxone 1 mg/kg/day was given intraperitoneally daily on days 0 to 21 in experiment I (acute stage) and on days 21 to 42 in experiment II (chronic stage). For the analysis of endogenous opiate and neurohumoral system, plasma beta-endorphin and cytokines were measured. The cytotoxic activity of lymphocytes was determined by Cr-release assay. Naloxone reversed hypotension produced by massive myocardial injury in experiment I. In experiment I, the severity of cardiac pathology and inflammatory cytokines were decreased in the naloxone-treated group associated with higher beta-endorphin level compared with the untreated group. In addition, naloxone induced a shift from Th1 cytokine toward Th2 cytokine balance. Thus, cytotoxic activities of lymphocytes against EL-4 tumor cells were lower in the treated group than in the untreated group in experiment I, but not in experiment II. Naloxone is beneficial for heart failure caused by EAM in the acute stage, but not in the chronic stage, due to decreasing cytotoxic activities of lymphocytes and to its neurohumoral modulating effects.

Topics: Acute Disease; Animals; Autoimmune Diseases; beta-Endorphin; Cell Line, Tumor; Cytokines; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Disease Models, Animal; Erythrocytes; Mice; Mice, Inbred C57BL; Myocarditis; Myocardium; Naloxone; Narcotic Antagonists; Radioimmunoassay

The aim was to test the therapeutic efficacy of naloxone, an opiate receptor antagonist, upon murine coxsackievirus B3 myocarditis with the analysis of neurohumoral kinetics.. Two week old C3H/He mice were inoculated with 10(3) plaque forming units of coxsackie B3 virus. Naloxone, 1 mg.kg-1.d-1, was given intraperitoneally daily on days 0-14 in experiment I, and on days 14-28 in experiment II. The treated groups were compared to infected controls in each experiment. For the analysis of the endogenous opiate and neurohumoral system, plasma beta endorphin and catecholamines were measured.. In experiment I, survival rate did not differ significantly between naloxone treated and untreated groups (11/15 v 8/15, p = NS). Pathological scores (infiltration and necrosis), myocardial virus titres, and plasma beta endorphin and catecholamine concentrations did not differ significantly between the two groups. In experiment II, survival rate (13/16 v 6/14, P < 0.05) was higher and cardiac pathology was less severe, with a lower incidence of congestive heart failure, in naloxone than in controls groups. In addition, beta endorphin and noradrenaline were significantly increased in the naloxone group compared to the control.. The endogenous opiate system is activated in congestive heart failure caused by severe myocardial damage in murine coxsackie B3 myocarditis, where an associated limitation of the sympathetic system may be present. Naloxone is beneficial in congestive heart failure caused by coxsackie B3 myocarditis because of its neurohumoral modulating effect.

Topics: Animals; beta-Endorphin; Coxsackievirus Infections; Heart Failure; Male; Mice; Mice, Inbred C3H; Myocarditis; Myocardium; Naloxone; Norepinephrine; Survival Rate