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Original Investigation
Jul/Aug 2017

Biochemical Effects of Exercise on a Fasciocutaneous Flap in a Rat Model

Author Affiliations
  • 1Department of Otolaryngology–Head and Neck Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
  • 2Department of Pathology, Anatomy, and Cell Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
JAMA Facial Plast Surg. 2017;19(4):303-310. doi:10.1001/jamafacial.2016.2162
Key Points

Question  What are the clinical and biochemical effects of exercise on the survival of pedicled fasciocutaneous flaps in a rat model?

Findings  In this experimental study comparing pedicled flap survival in 9 sedentary vs 9 voluntarily exercised adult male rats, exercise significantly decreased the amount of flap necrosis. Exercise dose–dependent flap survival correlated with statistically significant increased vascular endothelial growth factor levels and associated biochemical protein expression.

Meaning  Voluntary presurgical exercise increases pedicled fasciocutaneous flap survival in rats.


Importance  An overwhelming amount of data suggest that cardiovascular exercise has a positive effect on the mind and body, although the precise mechanism is not always clear.

Objective  To assess the clinical and biochemical effects of voluntary cardiovascular exercise on pedicled flaps in a rodent model.

Design, Setting, and Participants  Eighteen adult Sprague-Dawley male rats were randomized into a resting animal group (RAG) (n=9) and an exercise animal group (EAG) (n=9) for 14 days (July 23, 2013, through July 30, 2013). A pedicled transposition flap was performed on the ventral surface of the rat, and biopsy specimens were taken from the proximal, middle, and distal portions on postoperative days 0, 2, 5, and 9. Flap survival was analyzed planimetrically, and biopsy specimens were analyzed by hematoxylin-eosin–stained microscopy and immunoblotting. The housing, exercise, surgery, and analysis of the rats were conducted at a single basic science research laboratory at the tertiary care center campus of Thomas Jefferson University in Philadelphia, Pennsylvania.

Exposures  The rats were caged for 14 days or housed in a cage connected to an exercise wheel and pedometer.

Main Outcomes and Measures  Study measures were gross and micrographic necrosis and expression of proteins within cell survival and apoptosis pathways.

Results  A total of 18 rats were studied, 9 in the RAG and 9 in the EAG. the mean (SEM) amount of necrosis in flaps was 41.3% (3%) in the RAG rats and 10.5% (3.5%) in the EAG rats (P < .001). Immunoblotting revealed increased Caspase-9 activity resulting in poly–(adenosine diphosphate–ribose) polymerase 1 cleavage in the RAG vs the EAG, as well as lower phosphorylated protein kinase B (also known as Akt), signal transducer and activator of transcription 3, and total B-cell leukemia/lymphoma 2 protein levels. Throughout the postoperative period, the cumulative vascular endothelial growth factor A levels of the EAG flaps were significantly higher than those of the RAG flaps (2.30 vs 1.25 fold induction [FI], P = .002), with differences of 2.76 vs 1.54 FI in the proximal segment, 2.40 vs 1.20 FI in the middle segment, and 1.90 vs 0.79 FI in the distal segment. A similar response was noted when comparing phosphorylated Akt, with cumulative mean (SEM) p-Akt expression levels of 0.62 (0.04) for RAG and 1.98 (0.09) for EAG (P = .002 between the 2 groups).

Conclusions and Relevance  Voluntary preoperative exercise improves survival in pedicled fasciocutaneous flaps; the EAG rats had less necrosis, decreased apoptotic markers, and increased amounts of vascular endothelial growth factor A and prosurvival proteins. These results have implications to increase flap survival in other mammal populations, such as humans.

Level of Evidence  3.