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Controlled Super-Zero Cooling After Volumetric Muscle Loss Injury Improves MRI Metrics of Recovery in a Large Animal Model
Eddy C. Rios
*1, Daniah Al-Nafisee
2, Hiroshi Fujimaki
1, Francisco Batiz-Fabela
1, Mitchell Kennedy
1, Samantha Kroon
1, Monica Royo
1, Maria Bejar-Chapa
1, Bilal M. Chaudhry
1, Giorgio Giatsidis
11Surgery (Division of Plastics), UMass Chan School of Medicine, Worcester, MA; 2Surgery (Division of Plastic Surgery), University of Minnesota, Minneapolis, MN
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 translational swine model of VML (n=15) showed that daily post-injury treatment with controlled cooling fluid (CCF) increased recovery of maximal muscle torque (35±25 vs 12±6% recovery; p=0.00039) and decreased muscle fibrosis infiltration (15±22 vs 29±33%; p=0.044). We therefore hypothesized that in the same swine model of VML, CCF would increase PTM muscle size, decrease accessory muscle (AM) size compensation, and decrease both inflammation and fat fraction.
Methods: Left Peroneus Tertius muscle (PTM) VML injury was surgically induced in female (38-42 kg) Yucatan pigs; animals received no treatment (n=3) or CCF of the PTM (n=2). T1, T2, and Dixon series of Magnetic Resonance Imaging (MRI) were performed on post-injury day 35 (PID35), and all values were standardized against the contralateral PTM or the animal's bodyweight at time of MRI. Image J was used to extract the following primary outcomes: PTM size (cm^3/Kg), AM size (cm^3/Kg), left: right PTM fat fraction ratio, and left: right PTM inflammation ratio.
Results: Compared to controls, CCF-treated animals had significantly increased left PTM size (0.78±0.22 vs 0.36±0.09 cm^3/Kg; p=0.0084), non-significantly decreased left AM size (0.59±0.025 vs 0.70±0.13 cm^3/Kg; p=0.10), and non-significantly increased left: right PTM size ratio (0.88±0.54 vs 0.39±0.18; p=0.054). Animals receiving CCF also had non-significant reductions in left: right PTM fat fraction ratio (0.88±0.10 vs 1.00±0.22; p=0.21) and inflammation ratio (1.09±0.17% vs 1.20±0.28%; p=0.44).
Conclusions: In a translational large animal model, CCF seems to improve muscle size recovery on MRI, possibly mitigating accessory muscle compensation, muscular inflammation, and fat fraction. These results should be validated in a pilot clinical trial of CCF as a post-VML therapy.
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