The effect of muscle flap transposition to the fracture site on TNFalpha levels during fracture healing.
The trauma and sepsis that follow open fractures and wounds may lead to the production of various cytokines. Understanding wound healing requires a direct knowledge of the specific cytokines and the respective wound fluid levels that are present at the wound site. An animal model was designed that mimics the open fracture and the clinical repair of the human, high-energy open fracture. Canine right tibiae were fractured with a penetrating, captive-bolt device, then repaired in a standard clinical fashion using an interlocking intramedullary nail. Before primary wound closure, microdialysis probes were placed at the fracture site and in a muscle located at a contralateral site. Canines received one of the following experimental protocols: (1) tibial fracture (n = 5); (2) tibial fracture plus Staphylococcus aureus inoculation at the fracture site (n = 5); and (3) tibial fracture, S. aureus inoculation, and a rotational gastrocnemius muscle flap (n = 5). Microdialysis fluid samples were collected intermittently for 7 days. Tumor necrosis factor alpha (TNFalpha) levels at the fracture site were significantly elevated 3 to 34-fold (p<0.02), as compared with respective serum levels at all time points for all treatment groups. Fracture site TNFalpha levels were elevated (p<0.02) in days 1 through 6, as compared with the baseline and contralateral in all treatment groups. At days 1 through 6, the TNFalpha levels of the muscle flap group fracture site were significantly decreased by approximately 50 percent (p<0.05), as compared with the fractures without muscle flaps and regardless of additional S. aureus inoculation. On day 7, fracture site TNFalpha levels in all animal groups were similar, yet remained well above those of baseline TNFalpha. These results demonstrate that S. aureus does not further elevate TNFalpha levels in the presence of an open fracture and that a muscle flap reduces pro-inflammatory TNFalpha levels during early wound healing. This experimental model allows for the characterization of specific biological signals and cellular pathways that are influenced by bacterial infection and surgical closure. These data provide a scientific framework on which to judge or validate therapeutic regimens for open-fracture wound healing.
Brown
S A
SA
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. brown065@mc.duke.edu
Mayberry
A J
AJ
Mathy
J A
JA
Phillips
T M
TM
Klitzman
B
B
Levin
L S
LS
D000818:Animals; D004285:Dogs; D005594:Fracture Fixation, Intramedullary; D017102:Fracture Healing; D005597:Fractures, Open / Q000150:complications / Q000378:metabolism*; D017551:Microdialysis; D013203:Staphylococcal Infections / Q000150:complications; D013524:Surgical Flaps; D013978:Tibial Fractures / Q000378:metabolism / Q000601:surgery; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014946:Wound Infection / Q000150:complications
D014409:Tumor Necrosis Factor-alpha