Peripheral compartment syndrome (PCS) has a complex etiology, with limited treatment options and high patient morbidity. Animal models of PCS have been hampered by differences in cross-species anatomy, physiology, and the relative rarity of the naturally occurring syndrome in animals. In the present study, the combination of saline infusion with intermittent crushing of skeletal muscle consistently caused increased intracompartmental pressure, hypocalemia, and hypercreatinine-phophokinasemia, signs diagnostic of PCS. This method was used to evaluate both the standard PCS treatment, specifically a fasciotomy, and a regenerative medicine approach for treatment—consisting of a fasciotomy with local administration of a biologic scaffold material composed of porcine small intestinal submucosa extracellular matrix (SIS-ECM). The use of this SIS-ECM scaffold in conjunction with a fasciotomy was associated with myogenesis and constructive tissue remodeling in the SIS-ECM-treated animals. At 1 and 3 months after treatment innervated muscle tissue was present at the site of injury. No myogenesis was present in the fasciotomy only treated animals. RAM11+ macrophages, which are associated with constructive tissue remodeling, were present within the injury site in the SIS-ECM-treated animals at 1 month. The present study provides a reproducible animal model with which to study PCS, and shows the potential of a regenerative medicine approach to PCS treatment.
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References
1.
OwensB.D., KraghJ.F.Jr., MacaitisJ., SvobodaS.J., WenkeJ.C.Characterization of extremity wounds in Operation Iraqi Freedom and Operation Enduring Freedom. J Orthop Trauma, 21:254. 2007.
2.
OwensB.D., KraghJ.F.Jr., WenkeJ.C., MacaitisJ., WadeC.E., HolcombJ.B.Combat wounds in operation Iraqi Freedom and operation Enduring Freedom. J Trauma, 64:295. 2008.
3.
BrownK.V., RamasamyA., TaiN., MacLeodJ., MidwinterM., ClasperJ.C.Complications of extremity vascular injuries in conflict. J Trauma, 66:S145. 2009.
BrancoB.C., InabaK., BarmparasG., SchnurigerB., LustenbergerT., TalvingP., LamL., DemetriadesD.Incidence and predictors for the need for fasciotomy after extremity trauma: a 10-year review in a mature level I trauma centre. Injury, 2010[Epub ahead of print.]10.1016/j.injury.2010.07.243
6.
StarnesB.W., BeekleyA.C., SebestaJ.A., AndersenC.A., RushR.M.Jr.Extremity vascular injuries on the battlefield: tips for surgeons deploying to war. J Trauma, 60:432. 2006.
7.
PaiV.Acute compartment syndrome after rupture of the medial head of gastrocnemius in a child. J Foot Ankle Surg, 46:288. 2007.
FergusonR.E.Jr., PuL.L.Repair of the abdominal donor-site fascial defect with small intestinal submucosa (Surgisis) after TRAM flap breast reconstruction. Ann Plast Surg, 58:95. 2007.
SmithM., HooksV.H., JenkinsB.Patch repair of ileoanal pouch-vaginal fistula with Permacol collagen implant. Am Surg, 73:514. 2007.
15.
TurnerN.J., YatesA.J., WeberD.J., QureshiI.R., Beer StolzD., GilbertT.W., BadylakS.F.Xenogeneic extracellular matrix as an inductive scaffold for regeneration of a functioning musculotendinous junction. Tissue Eng Part A, 16:3309. 2010.
16.
BadylakS., KokiniK., TulliusB., Simmons-ByrdA., MorffR.Morphologic study of small intestinal submucosa as a body wall repair device. J Surg Res, 103:190. 2002.
17.
ClarkeK.M., LantzG.C., SalisburyS.K., BadylakS.F., HilesM.C., VoytikS.L.Intestine submucosa and polypropylene mesh for abdominal wall repair in dogs. J Surg Res, 60:107. 1996.
18.
BrownB.N., ValentinJ.E., Stewart-AkersA.M., McCabeG.P., BadylakS.F.Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component. Biomaterials, 30:1482. 2009.
19.
ValentinJ.E., TurnerN.J., GilbertT.W., BadylakS.F.Functional skeletal muscle formation with a biologic scaffold. Biomaterials, 31:7475. 2010.
AgrawalV., BrownB.N., BeattieA.J., GilbertT.W., BadylakS.F.Evidence of innervation following extracellular matrix scaffold-mediated remodelling of muscular tissues. J Tissue Eng Regen Med, 3:590. 2009.
22.
BeraldoS., DoddsS.R.Lower limb acute compartment syndrome after colorectal surgery in prolonged lithotomy position. Dis Colon Rectum, 49:1772. 2006.
23.
KingT.W., LermanO.Z., CarterJ.J., WarrenS.M.Exertional compartment syndrome of the thigh: a rare diagnosis and literature review. J Emerg Med, 39:e93. 2010.
DalyK., Stewart-AkersA., HaraH., EzzelarabM., LongC., CorderoK., JohnsonS., AyaresD., CooperD., BadylakS.F.Effect of the alphaGal epitope on the response to small intestinal submucosa extracellular matrix in a nonhuman primate model. Tissue Eng Part A, 15:3877. 2009.
29.
MaheshwariR., TaitsmanL.A., BareiD.P.Single-incision fasciotomy for compartmental syndrome of the leg in patients with diaphyseal tibial fractures. J Orthop Trauma, 22:723. 2008.
30.
ValentinJ.E., Stewart-AkersA.M., GilbertT.W., BadylakS.F.Macrophage participation in the degradation and remodeling of extracellular matrix scaffolds. Tissue Eng Part A, 15:1687. 2009.
31.
ArnoldL., HenryA., PoronF., Baba-AmerY., van RooijenN., PlonquetA., GherardiR.K., ChazaudB.Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J Exp Med, 204:1057. 2007.
32.
Bar-AmY., AnugA.M., ShaharR.Femoral compartment syndrome due to haemangiosarcoma in the semimembranosus muscle in a dog. J Small Anim Pract, 47:286. 2006.
33.
RadkeH., SprengD., SigristN., LangJ., BornandV., SchawalderP.Acute compartment syndrome complicating an intramuscular haemangiosarcoma in a dog. J Small Anim Pract, 47:281. 2006.
GershuniD.H., HargensA.R., LieberR.L., O'HaraR.C., JohanssonC.B., AkesonW.H.Decompression of an experimental compartment syndrome in dogs with hyaluronidase. Clin Orthop Relat Res, 197:295. 1985.
36.
RicciM.A., CorbisieroR.M., MohamedF., GrahamA.M., SymesJ.F.Replication of the compartment syndrome in a canine model: experimental evaluation of treatment. J Invest Surg, 3:129. 1990.
37.
BaiY.H., TakemitsuM., AtsutaY., TakemitsuY.Pathology study of rabbit calf muscles after repeated compression. J Orthop Sci, 3:209. 1998.
38.
LiQ., BaiY., XuY., YuH.Autografting satellite cells to repair damaged muscle induced by repeated compression: an animal model. Foot Ankle Int, 31:706. 2010.
39.
VollmarB., WestermannS., MengerM.D.Microvascular response to compartment syndrome-like external pressure elevation: an in vivo fluorescence microscopic study in the hamster striated muscle. J Trauma, 46:91. 1999.
40.
PedowitzR.A., GershuniD.H., SchmidtA.H., FridenJ., RydevikB.L., HargensA.R.Muscle injury induced beneath and distal to a pneumatic tourniquet: a quantitative animal study of effects of tourniquet pressure and duration. J Hand Surg Am, 16:610. 1991.
41.
ValentinJ.E., BadylakJ.S., McCabeG.P., BadylakS.F.Extracellular matrix bioscaffolds for orthopaedic applications. A comparative histologic study. J Bone Joint Surg Am, 88:2673. 2006.
42.
JarvinenM.Healing of a crush injury in rat striated muscle. 2. a histological study of the effect of early mobilization and immobilization on the repair processes. Acta Pathol Microbiol Scand A, 83:269. 1975.
43.
JarvinenM.Healing of a crush injury in rat striated muscle. 3. A micro-angiographical study of the effect of early mobilization and immobilization on capillary ingrowth. Acta Pathol Microbiol Scand A, 84:85. 1976.
44.
JarvinenM.Healing of a crush injury in rat striated muscle. 4. Effect of early mobilization and immobilization on the tensile properties of gastrocnemius muscle. Acta Chir Scand, 142:47. 1976.
45.
BadylakS.F., ValentinJ.E., RavindraA.K., McCabeG.P., Stewart-AkersA.M.Macrophage phenotype as a determinant of biologic scaffold remodeling. Tissue Eng Part A, 14:1835. 2008.
46.
BrennanE.P., TangX.H., Stewart-AkersA.M., GudasL.J., BadylakS.F.Chemoattractant activity of degradation products of fetal and adult skin extracellular matrix for keratinocyte progenitor cells. J Tissue Eng Regen Med, 2:491. 2008.
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