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Controlled Regional Hypothermia Improves Functional Recovery After Skeletal Muscle Injury in Rats
Bilal Chaudhry, MD; Hiroshi Fujimaki, MD, PhD; Daniah ALNafisee, MD; Eddy Rios, BS; Nicole Ayres, BS; Chen Ryan, BA; Yuying Zhang, BS; Adrienne Conza, BA; Janice F Lalikos, MD; Giorgio Giatsidis, MD, PhD
RESICE (Restorative & Regenerative Surgery Innovation Center, Division of Plastic Surgery, University of Massachusetts Medical School.
Background: Volumetric muscle loss (VML) injury is associated with a majority of the 150,000 open fractures in the U.S annually. Current therapies including physical therapy lead to limited recovery with 50% of patients with severe injuries developing chronic disability. Cooling has been shown to assist in muscle repair by reducing fibrosis and damage secondary to exacerbation of inflammatory response. In a murine model, we hypothesized that controlled regional hypothermia stimulates muscle regeneration and reduces fibrosis, improving recovery following VML. Materials and Methods?? 20 female Sprague Dawley rats were divided into two groups: control and controlled hypothermia (CH). VML injuries were surgically induced in the Tibialis Anterior muscle. Outcomes assessed at 0, 3, 14, and 30 days post-injury included percent recovery of maximum isometric torque (MIT, Nm), fatigue index (%), treadmill endurance (time) and histology (H&E, Masson's trichrome for fibrosis, and CD68 for macrophages). Results?? At 30 days, CH group showed 72.2% ±50.2 recovery in pre-injury MIT versus 42.1%±50.3 in controls (p=.015). Treated group also showed higher resistance to fatigue (71.8%±49.2 vs 45.9 ±48.2; p=.028) and better recovery of pre-injury treadmill endurance (103.9% ±59.3 vs 37.6± 74.7; p=.0004). Histologically, treated muscles showed significantly less fibrosis (49.2%± 12.9 vs 81.4± 14; p= .0026) and macrophage infiltration (13.8%±9.8 vs 69.6%± 44.5 p=.0003). Conclusions?? Our findings suggest that controlled regional hypothermia after VML promotes recovery in rodents. A larger animal model and further analyses will help validate these results and identify biological processes involved.
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