Secondary Burn Progression Mitigated by an Adenosine 2A Receptor Agonist

Abstract

Background Current burn therapy is largely supportive with limited therapies to curb secondary burn progression. Adenosine 2A receptor (A2AR) agonists have anti-inflammatory effects with decreased inflammatory cell infiltrate and release of pro-inflammatory mediators. Using a porcine comb burn model, we examined whether A2AR agonists could mitigate burn progression. Study Design Eight full-thickness comb burns (4 prongs with 3 spaces per comb) per pig were generated with the following specifications: temperature 115° C, 3 kg force, and 30 second application time. In a randomized fashion, animals (4 per group) were then treated with A2AR agonist (ATL-1223, 3 ng/kg/min, intravenous infusion over 6 hours) or vehicle control. Necrotic interspace development was the primary outcome and additional histologic assessments were conducted. Results Analysis of unburned interspaces (72 per group) revealed that ATL-1223 treatment decreased the rate of necrotic interspace development over the first 4 days following injury (p<0.05). Treatment significantly decreased dermal neutrophil infiltration at 48 hours following burn (14.63±4.30 vs 29.71±10.76 neutrophils/high-power field, p=0.029). Additionally, ATL-1223 treatment was associated with fewer interspaces with evidence of microvascular thrombi through post-burn day 4 (18.8% vs 56.3%, p=0.002). Two weeks following insult, the depth of injury at distinct burn sites (adjacent to interspaces) was significantly reduced by ATL-1223 treatment (2.91±0.47 vs 3.28±0.58 mm, p=0.038). Conclusion This work demonstrates the ability of an A2AR agonist to mitigate burn progression through dampening local inflammatory processes. Extended dosing strategies may yield additional benefit and improve cosmetic outcome in those with severe injury.

Fish Skin Grafts Affect Adenosine and Methionine Metabolism during Burn Wound Healing

“…Adenosine receptor activation has also been shown to reduce neutrophil adhesion, activation, and infiltration [58][59][60]. In burn wounds specifically, Adenosine A 2A receptor agonists have recently been shown to mitigate FT burn wound healing by dampening the inflammatory response in a porcine burn wound model [61]. Adenosine concentrations have also been reported to be elevated in human burn wound blister fluids [62].…”