Abstract 13053: Dehydroascorbic Acid Therapy Attenuates Septic Cardiomyopathy In Mice
Background: Sepsis induces a complex response to bacterial infection, trauma, burns or abdominal surgery. Septic cardiomyopathy is a well-described complication of septic shock that is characterized by up-regulation of cardio-suppressive chemokines/cytokines. Recent research suggests that vitamin C is protective in sepsis, but its role in septic cardiomyopathy is unknown. Therefore we examined the effect of clinically relevant vitamin C (ascorbic acid, AscA or dehydroascorbic acid, DHA) administration in the setting of lipopolysaccharide (LPS) -associated cardiomyopathy.
Methods and Results: C57BL/6 mice were exposed to LPS (10μg/g of body weight) 30 minutes prior to receiving saline, AscA or DHA (200mg/kg). After 16 hours of LPS exposure hearts were assessed by echocardiography and subsequently harvested for determination of cardiac chemokine/cytokine expression (QPCR) and protein quantification (ELISA, Western Blot). LPS promoted cardiac NFκB activation and neutrophil sequestration, increased myocyte pro-inflammatory chemokine expression (KC, LIX, MCP-1, MIP-2) and impaired left ventricular (LV) function. Unlike AscA, DHA administration prevented NFκB activation, reduced neutrophil sequestration, decreased chemokine expression and restored endothelial nitric oxide synthase activity. DHA treatment in LPS exposed mice prevented the reduction in LV ejection fraction (33.67 ± 2.76 vs 62 ± 5.02, p<0.001), fractional shortening (15.67 ± 1.52 vs 33 ± 3.6, p<0.005), stroke volume (13.33 ± 1.19 vs 27.5 ± 1.64 ml, p<0.001) and cardiac output (3758 ± 349 vs 13740 ± 1607 ml/min, p<0.05). These results indicate a prominent cardio-protective effect for DHA, but not AscA. Further, they are consistent with the known inability of cardiomyocytes to accumulate vitamin C when incubated with AscA.
Conclusions: Dehydroascorbic acid therapy attenuates sepsis-related contractile dysfunction and may represent a novel treatment for septic cardiomyopathy.
- © 2010 by American Heart Association, Inc.