Antioxidant vitamin therapy alters burn trauma-mediated cardiac NF-kappa Bactivation and cardiomyocyte cytokine secretion

Background: This study examined the effects of antioxidant vitamins A, C, a nd E on nuclear transcription factor-kappa B (NF-kappaB) nuclear translocat ion, on secretion of inflammatory cytokines by cardiac myocytes, and on car diac function after major burn trauma. Methods: Adult rats were divided into four experimental groups: group I, sh ams; group II, shams given oral antioxidant vitamins (vitamin C, 38 mg/kg; vitamin E, 27 U/kg; vitamin A, 41 U/kg 24 hours before and immediately afte r burn); group III, burns (third-degree scald burn over 40% total body surf ace area) given lactated Ringer's solution (4 mL/kg/% burn); and group IV, burns given lactated Ringer's solution plus vitamins as described above. He arts were collected 4, 8,12, and 24 hours after burn to assay for NF-KB nuc lear translocation, and hearts collected 24 hours after burn were examined for cardiac contractile function or tumor necrosis factor-alpha secretion b y cardiomyocytes. Results: Compared with shams, left ventricular pressure was lower in burns given lactated Ringer's solution (group]III) (88 +/- 3 vs. 64 +/- 5 mm Hg,p < 0.01) as was +dP/dt max (2,190 <plus/minus> 30 vs. 1,321 +/- 122 mm Hg/s ) and -dP/dt max (1,775 +/- 71 vs. 999 +/- 96 mm Hg,p < 0.01). Burn injury in the absence of vitamin therapy (group III) produced cardiac NF-<kappa>B nuclear migration 4 hours after burn and cardiomyocyte secretion of tumor n ecrosis factor-alpha, interleukin-1 beta, and interleukin-6 by 24 hours aft er burn. Antioxidant therapy in burns (group IV) improved cardiac function, producing left ventricular pressure and +/- dP/dt (82 +/- 2 mm Hg, 1,880 /- 44 mm Hg, and 1,570 +/- 46 mm Hg/s) comparable to those measured in sham s. Antioxidant vitamins in burns inhibited NF-KB nuclear migration at all t imes after burn and reduced burn-mediated cytokine secretion by cardiomyocy tes. Conclusion: These data suggest that antioxidant vitamin therapy in burn tra uma provides cardioprotection, at least in part, by inhibiting translocatio n of the transcription factor NF-KB and interrupting cardiac inflammatory c ytokine secretion.