Burn Wound Excision Drives Acute Hypermetabolism in Mice with Scald Burns

Abstract

Hypermetabolism (elevated resting energy expenditure) is a hallmark of the pathophysiological response to burns. The contribution of wound excision to acute burn-induced hypermetabolism remains unclear. Importantly, while burn wound excision is a standard component of clinical burn care, it is not typically included in rodent models of burn injury. Here, we tested the hypothesis that burn wound excision drives the acute hypermetabolic response to burn trauma. C57BL/6J mice (n=12-18 per group; ~6-weeks old; 50% male) were acclimated to thermoneutral housing (30C) for 6-weeks. All mice underwent baseline body composition scans and metabolic phenotyping to determine total (TEE) and resting energy expenditure (REE). Mice were then randomized to either sham (control), scald burn (burn), wound excision (excision), or scald burn followed by immediate wound excision (burn+excision) groups. Burns and wound excisions involved ~15% of the body surface area. Mice then recovered for 14 days while individually housed in metabolic phenotyping cages. At day 14 post-injury, mice underwent a second body composition scan prior to euthanasia. There were no fatalities in the control or burn groups, whereas 23% (n=7) and 34% (n=11) of mice in the excision and burn+excision groups died or were euthanized during the 14-day recovery period. Male and female mice exhibited broadly similar responses to injury in terms of REE and TEE. Compared to control, REE was greater in burn (47%), excision (102%), and burn+excision groups (136%) during the first week post-injury (P<0.001 for all). Compared to control mice, wound excision (alone or following burns) resulted in a greater acute loss in body mass than burn injury alone. However, this cachectic response was more sustained in male mice compared to females. Similarly, wound excision (alone or following burns) resulted in greater bone mineral content and density loss compared to sham and burn alone in both sexes. Wound excision is a key contributor to the hypermetabolic and cachectic response to burn trauma in mice. We posit that rodent studies aiming to recapitulate burn-induced hypermetabolism and cachexia should include burn wound excision to better model the clinical sequelae to burns.