Prevention of cardiac dysfunction in septic mice by glucan phosphate through inhibition of cardiac MIF and apoptosis

Myocardial dysfunction is a major consequence of septic shock and contributes to the high mortality of sepsis. Macrophage migration inhibitory factor (MIF) has been indicated as a major triggering factor for cardiac myocyte apoptosis and cardiac dysfunction during septic shock. We have reported that glucan phosphate (GP) significantly increased survival in a murine model of sepsis induced by cecal ligation and puncture (CLP). In the present study, we examined the effect of GP on myocardial function in CLP sepsis. GP was administered to ICR/HSD mice one hr before induction of CLP. Sham surgical operated mice served as control. Cardiac function was significantly decreased six hrs after CLP‐induced sepsis compared with sham control. CLP significantly increased MIF expression by 109.8% in the myocardium and increased cardiac myocyte apoptosis by 7.8 fold compared with sham control. GP administration, however, prevented cardiac dysfunction, reduced CLP‐increased MIF expression by 207.6%, and decreased cardiac myocyte apoptosis by 51.2% compared with untreated CLP mice. GP also prevented the decrease in phospho‐Akt and Bcl‐2 in the myocardium of CLP‐induced septic mice. The results show that both increased MIF expression and cardiac myocyte apoptosis contribute to the cardiac dysfunction in septic shock. Prevention of cardiac dysfunction by GP involves decreases in MIF expression and reduction of cardiac myocyte apoptosis in septic mice.