Moderate systemic hypothermia decreases burn depth progression

Abstract

Background: Therapeutic hypothermia has been proposed to be beneficial in an array of human pathologies including cardiac arrest, stroke, traumatic brain and spinal cord injury, and hemorrhagic shock. Burn depth progression is multifactorial but inflammation plays a large role. Because hypothermia is known to reduce inflammation, we hypothesized that moderate hypothermia will decrease burn depth progression.

Methods: We used a second-degree 15% total body surface area thermal injury model in rats. Burn depth was assessed by histology of biopsy sections. Moderate hypothermia in the range of 31-33°C was applied for 4h immediately after burn and in a delayed fashion, starting 2h after burn. In order to gain insight into the beneficial effects of hypothermia, we analyzed global gene expression in the burned skin.

Results: Immediate hypothermia decreased burn depth progression at 6h post injury, and this protective effect was sustained for at least 24h. Burn depth was 18% lower in rats subjected to immediate hypothermia compared to control rats at both 6 and 24h post injury. Rats in the delayed hypothermia group did not show any significant decrease in burn depth at 6h, but had 23% lower burn depth than controls at 24h. Increased expression of several skin-protective genes such as CCL4, CCL6 and CXCL13 and decreased expression of tissue remodeling genes such as matrix metalloprotease-9 were discovered in the skin biopsy samples of rats subjected to immediate hypothermia.

Conclusions: Systemic hypothermia decreases burn depth progression in a rodent model and up-regulation of skin-protective genes and down-regulation of detrimental tissue remodeling genes by hypothermia may contribute to its beneficial effects.