Glucosamine modulates sepsis‐induced changes in cardiac performance

Abstract

Recent studies suggest an anti‐inflammatory role for glucosamine (GlcN). We tested the hypothesis that GlcN treatment in septic rats prevents defects in cardiac performance. Cecal ligation and puncture (CLP) or sham surgery was performed in male Sprague‐Dawley rats (250‐300g). CLP rats were further randomized to receive GlcN (0.3 mg/g) or saline by ip injection. Echocardiography was performed prior to and 24 hours post surgery. Cardiac dimensions in sham rats were unchanged over this time. In contrast, there was a 6 fold increase in IVSd and PWd and a 5‐fold reduction in LVEDD and LVESD in CLP rats. GlcN treatment attenuated these responses by approximately 50%. Reductions in end‐diastolic volume (EDV), stroke volume (SV) and cardiac output (CO) in CLP rats were also attenuated by GlcN. Fractional shortening, however, was similar in all groups. These data suggest that impaired cardiac performance in CLP rats is due to a reduction in LV filling rather than to a defect in cardiac function per se. CTD110.6 immunoreactivity, a marker of protein O‐GlcNAcylation, was increased in hearts from GlcN‐treated CLP rats. GlcN treatment also increased survival (93%) in CLP rats at 24 hrs compared to saline‐treated CLP rats (70%). It is proposed that GlcN improves cardiac performance and survival in CLP rats by a mechanism involving an increase in protein O‐GlcNAcylation and inhibition of inflammatory pathways.