Effects of activated macrophages and fibroblast growth factor on random skin flap survival in swine.
OBJECTIVE
To examine the effect of application of activated autologous macrophages and basic fibroblast growth factor (FGF) on random skin flap survival in swine.


METHODS
A randomized nonblinded controlled trial. According to a standard design, six dorsally based, random-pattern skin flaps were raised in each of 12 Yorkshire pigs.


METHODS
Twenty-five milliliters of blood is harvested from each animal 20 to 24 hours prior to flap creation. Monocytes are isolated, placed in culture medium, and then activated by the addition of platelet-derived growth factor (PDGF) and tissue growth factor beta (TGF-alpha). Following an 18-hour incubation period, the monocytes are decanted and quantified, and their viability confirmed. These cells are then infused into the wound bed of the treatment flaps immediately following flap creation, and FGF is added prior to flap closure. The position of treatment and control flaps is systematically varied with regard to anterior-to-posterior and side-to-side flap positions within each animal. The area of superficial flap necrosis is evaluated on postoperative day 7, digitally scanned, and analyzed using graphics software. Control flaps are elevated similarly, but receive no placebo treatment.


RESULTS
Two-way analysis of variance (ANOVA) demonstrated nonsignificant differences between pig side and anterior, middle, and posterior flap positions within treatment and control flap groups. Using side and position pooled data, a one-way ANOVA showed no statistically significant differences between treatment and control flaps.


CONCLUSIONS
The cellular and biochemical events following creation of a surgical wound are complex and incompletely understood. Our attempt to augment the natural role of the macrophage in wound healing by employing cytokines to activate these cells and to accelerate their arrival by implanting them into the wound bed failed to enhance flap survival. Further study is warranted to ascertain the details of wound healing, particularly with respect to cytokine concentrations and the timing of their roles, if we are to find a clinically applicable means of enhancing flap survival.
Bach
K K
KK
Department of Otolaryngology-Head and Neck Surgery, Naval Medical Center, San Diego, California 92134-5000, USA.
Cupp
C
C
Brewster
D
D
Wester
D
D
Keefe
M
M
D000818:Animals; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006085:Graft Survival / Q000502:physiology*; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D011897:Random Allocation; D013524:Surgical Flaps / Q000502:physiology*; D013552:Swine
D005346:Fibroblast Growth Factors