Hideharu Tanaka

Reduced fluid volume requirement for resuscitation of third-degree burns with high-dose vitamin C

The effects of high-dose vitamin C therapy (170 mg, 340 mg, and 680 mg/kg/day) were evaluated in 70% body surface area third-degree burns in guinea pigs that were resuscitated with 1 ml/kg/%burn Ringers lactate solution. The water content measurements of the burned skin at 24 hours after burn injury in the vitamin C-treated groups were significantly lower than those of the control group (1 ml/kg/%burn) and those of the standard resuscitation group (4 ml/kg/%burn). The cardiac outputs in the group that received 340 mg vitamin C were significantly higher than those of the control group but not significantly different than those of the standard therapy group at 2 hours after burn injury and thereafter. In comparison with the regimen of 340 mg vitamin C, the regimen of 680 mg vitamin C was no more beneficial, and the regimen of 170 mg was less effective. With administration of adjuvant high-dose vitamin C, we were able to reduce the total 24-hour resuscitation volume from 4 ml/kg/%burn to 1 ml/kg/%burn, while a comparable cardiac output was maintained.

Effects of cimetidine on fluid requirement during resuscitation of third-degree burns.

Seventy percent body surface area third-degree burns were produced in four groups of six guinea pigs each, after which all were resuscitated with Ringers lactate solution. Group 1 received 4 ml/kg/%burn. Group 2 received 1 ml/kg/%burn with cimetidine, which was begun at 0.5 hours after burn injury. Group 3 received 1 ml/kg/%burn with cimetidine, which was begun at 1 hour after burn injury. Group 4 received 1 ml/kg/%burn without cimetidine. There were no significant differences among any of the groups in blood pressures or heart rates during the study period. Group 4 showed significantly higher hematocrit values than group 2 at 4 hours after burn injury and thereafter. The cardiac outputs of group 2 were the same statistically as those of group 1. The cardiac outputs of group 3 were significantly lower than those that received cimetidine early (group 2), though still higher than those of the 1 ml control group (group 4) at 4 hours after burn injury and thereafter. At 24 hours after burn injury, the water content of the burned skin of group 2 was significantly lower than that of the other groups. We conclude that in third-degree burns, cimetidine therapy can effectively reduce burn edema and the amount of required resuscitation fluid. Early administration is better than late administration of cimetidine.

Protective effects of a free radical scavenger, MCI‐186, on high‐glucose–induced dysfunction of human dermal microvascular endothelial cells

Functional damage to microvascular endothelial cells by hyperglycemia is thought to be one of the critical risk factors in the impaired wound healing seen with diabetes mellitus. It is also thought that free radical stress plays a significant role in this endothelial cell dysfunction. In the present study, the effect of a free radical scavenger, MCI 186, on the endothelial cell dysfunction of cultured cells induced by high‐glucose conditions was studied. Human dermal microvascular endothelial cells were cultured with high‐glucose medium (50 mM) with or without MCI‐18 6 (10 μM) for 7 days. Fifty mM mannitol was used as an osmotic control in this study. After this treatment, cell proliferation, activation of mitogen‐activated protein kinase (MAPK), the level of apoptosis, and caspase‐3 activation induced by removal of growth factors or tumor necrosis factor‐α treatment were studied. High‐glucose conditions significantly decreased cell proliferation and increased apoptosis levels with the activation of caspase‐3 induced by growth factor removal. The high‐glucose condition significantly activated MAPK. MCI‐186 treatment improved cellular proliferation and reduced apoptosis and caspase‐3 activation induced by high‐glucose conditions. MCI‐186 also inhibited the activation of MAPK. On the other hand, MCI‐186 did not alter the level of apoptosis and caspase‐3 activation induced by TNF‐α treatment. In conclusion, we suggest that MCI‐186 may be beneficial for improving the endothelial cell dysfunction induced by hyperglycemia.