(WHS-P4.03) EVALUATION OF SUBCUTANEOUS COMBINATION IBUPROFEN AND RESOLVIN D2 THERAPY TO MITIGATE BURN PROGRESSION
Friday, May 17, 2024
10:30 AM – 11:30 AM East Coast USA Time
Introduction: Thermal injuries are common to all military conflicts. Difficulties treating partial-thickness burns in the field are further complicated by their propensity to progress/convert to deep-partial or full-thickness burns within the first 24 hours of injury. It is hypothesized that burn conversion (deepening) occurs as a function of irregular perfusion linked to inflammation, which ultimately causes progressive necrosis in the wound. This study hypothesizes that subcutaneous administration of inflammation mitigating Ibuprofen and Resolvin D2, in a porcine model of burn progression, will prevent partial-thickness thermal burns from progressing to deep partial/full-thickness injuries, potentially improving wound healing outcomes. Materials and
Methods: To create partial-thickness burns in isoflurane anesthetized Yorkshire swine (also provided Buprenorphine SR for pain management), a 100°C heated 6 cm diameter brass cylinder was applied to the dorsum, to create ten burns per animal. An N of 6 animals were used; all 6 received the following treatments (2 wounds per treatment/animal): 1. Gauze (standard of care control), 2. Saline (vehicle control) 3. Ibuprofen (0.1 mg/mL) 4. Resolvin (0.05 mg/mL) 5. Combination treatment of Ibuprofen and Resolvin D2 at the same doses. Treatments were injected 3 hours post-injury and once again 24 hours later to simulate a prolonged field care (PFC) scenario. Before the burn injury and at pre-assigned time points post-burn (days 0, 1, 3, 7, 14, 21, and 28), wounds were imaged (Digital, Silhouette, MolecuLight, Moor Laser Doppler Imaging) and biopsies harvested. Half of the biopsy was evaluated histologically by H&E and immunohistochemistry (IHC) to determine the depth (normalized % of dermal depth) of damaged tissue and wound healing over the experimental period. Remaining biopsy samples were preserved for proteomic analysis.
Results: A one-way Analysis of Variance (ANOVA) was employed to determine that, 24 hours after injury, combination therapies of Ibuprofen and Resolvin D2 prevented burns from progressing to deep partial-thickness burns (55.8 ±21.4%) (p < 0.0001), whereas the military standard of care (Gauze) did not (66.6 ±21.9%). In addition, all experimental treatments reduced the lateral size (surface area) of burn injuries compared to Gauze, albeit not to a statistically significant degree.
Conclusions: Therapies already available in the field (Ibuprofen) and those less so (Resolvin D2) have previously displayed the ability to mitigate injury severity by lessening the degree of inflammation. We have shown here that while individual therapies may improve wound healing outcomes compared to the current standard of care, it may be the case that therapies used in concert, delivered directly to the injury, with varying mechanisms of action, can provide even greater efficacy.