Effects of high-dose vitamin c administration on bacterial translocation and lung neutrophil sequestration in burned mice

Severe burn injury produces shock and induces acute gastrointestinal derangements that may disrupt mucosal integrity and facilitate bacterial translocation (BT) to mesenteric lymph nodes, accompanied by endotoxemia. Antioxidant treatments may be beneficial after shock by acting as scavenger agents for highly reactive oxygen intermediates. We studied the effects of high dosages of vitamin C, a water-soluble antioxidant, on the incidence of BT and on levels of lung myeloperoxidase in burned mice. Myeloperoxidase is primarily found in neutrophils, and levels of myeloperoxidase in tissues reflect neutrophil sequestration. The doses of vitamin C used were equivalent on a weight basis to 1 gm/hr administered to humans over a 24-hour period, doses that have shown efficacy in improvement of resuscitation in other experimental burn models and currently are being used in clinical trials in patients with burns. Mice were anesthetized and received 32% total body surface area, full-thickness burn injury to the dorsum, followed by injection of 1 ml of Ringer’s lactate (RL) for resuscitation. Mice were divided into three groups: (1) unburned, received anesthesia and RL injections; (2) burned, received vitamin C (14 mg/kg/hr) in 1 ml RL by intraperitoneal injection immediately after burn and via subcutaneous injection (0.5 ml) at 6 and 12 hours after burn; (3) burned, received identical injections of RL alone (control animals). Mesenteric lymph nodes were removed by use of sterile technique at 24 hours after burn and cultured; any growth was considered evidence of BT. The incidence of BT in burned mice was not altered by administration of vitamin C (normal, 10% BT; burn, 41.37% BT; burn + vitamin C, 45.83% BT). Similarly, burned animals that received vitamin C or RL alone did not differ in the levels of myeloperoxidase in the lungs (normal, 0.015 ± 0.003 U/gm; burn, 0.2231 ± 0.029 U/gm; burn + vitamin C, 0.281 ± 0.041 U/gm). The inclusion of high dosages of vitamin C in the initial resuscitation fluid followed by two dosages after burn injury did not decrease the incidence of BT at 24 hours after burn; in addition, the amount of lung myeloperoxidase was not altered. Measurement of venous blood gases at 12 hours after burn demonstrated severe metabolic acidosis in burned mice, with no difference between burn groups treated with vitamin C and untreated mice. This murine model of controlled burn injury did not demonstrate physiologic improvement after treatment with high-dose vitamin C.