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Controlled Super-Zero Cooling After Volumetric Muscle Loss Injury Improves Functional Recovery in a Large Animal Model.
Eddy C. Rios
*, Daniah Al-Nafisee, Hiroshi Fujimaki, Francisco Batiz-Fabela, Mitchell Kennedy, Samantha Kroon, Monica Royo, Bilal M. Chaudhry, Giorgio Giatsidis
Division of Plastic Surgery, UMass Chan School of Medicine, Worcester, MA
Background: Over 40,000 traumatic volumetric muscle loss (VML) injuries occur annually in the US. Even ~20% muscle loss causes disproportionate lasting strength deficits of 30-90%. The current gold standard, physical therapy, only achieves partial functional recovery of 17-58%. Our prior murine model of VML showed that optimized post-injury treatment with controlled cooling (CC) improved recovery of baseline maximal muscle torque (MMT; +30%) and resistance to fatigue (RF; +66%). We hypothesized CC would have similar results in a large animal model of VML.
Methods: Left Peroneus Tertius muscle (PTM) VML injury was surgically induced in female (38-42 kg) Yucatan pigs; animals received no treatment (n=10) or CC of the PTM (n=5). Outcomes included post-injury day 35 (PID35) recovery of pre-injury MMT, PID35 strength in newton-centimeters per gram of PTM (ncm/g), PID35 recovery of pre-injury RF, and recovery of baseline activity levels (step count). PID35 muscle histology stains were also performed to assess % fibrosis infiltration (Masson's Trichrome).
Results: Compared to controls, CC-treated animals had significantly improved recovery of pre-injury MMT (35±25% vs 12±6%; p=0.00039), PID35 PTM strength per gram (3.7±4.7 ncm/g vs 1.5±1.4 ncm/g; p=0.017), and recovery of RF (38±24% vs 18±14%; p=0.0011). CC non-significantly improved recovery of activity level (123±174% vs 67±62%; p=0.12) and significantly decreased fibrosis infiltration (15±22% vs 29±23%; p=0.044).
Conclusions: In a translational large animal model, CC seems to promote functional recovery and modulate post-injury fibrosis. These results should be validated with further molecular analyses before a pilot clinical trial.
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