J. S. Brandenburg1, R. M. Clark1, B. B. Coffman4, G. Sharma2, H. J. Hathaway3, E. R. Prossnitz2, T. R. Howdieshell1,3 1University Of New Mexico HSC,Surgery,Albuquerque, NM, USA 2University Of New Mexico HSC,Molecular Medicine,Albuquerque, NM, USA 3University Of New Mexico HSC,Cell Biology,Albuquerque, NM, USA 4University Of New Mexico HSC,Pathology,Albuquerque, NM, USA
Introduction: Sex differences in susceptibility to ischemia/reperfusion injury have been documented in humans. Premenopausal women have a lower risk of ischemic heart disease than age-matched men, whereas after menopause, the risk is similar or even higher in women. However, little is known about the effects of sex on cutaneous wound revascularization.
Methods: A cranial-based, peninsular-shaped myocutaneous flap was surgically created on the dorsum of 10-12 week old male (n=10) and female (n=10) C57BL6 mice. Planimetric analysis of digital photographic images was utilized to determine flap viability. Real-time flap perfusion, ischemia, and functional revascularization was determined by laser speckle contrast imaging (LSCI). Image analysis of CD31-immunostained sections confirmed flap microvascular anatomy, density, and surface area. Values are expressed as means ± SEM. Student’s t test was performed when comparing two groups, and two-way ANOVA used when comparing multiple groups. Statistical significance was accepted at a p value < 0.05.
Results: Flaps created on female mice were engrafted to the recipient site resulting in nearly complete viability at post-operative day 10. In contrast, distal full thickness myocutaneous necrosis was evident at 10 days post-surgery in male mice (percent flap necrosis: female 5.8 ± 0.9% versus male 30.8 ± 4.7%, p < 0.05). Over the 10 day study interval, LSCI documented functional flap revascularization in all regions of interest (ROI) in female mice, but minimal distal flap reperfusion in male mice (day 10 distal ROI perfusion: female 191.5 ± 9.2 PU versus male 138.9 ± 11.7 PU, p < 0.05). Day 10 histologic sections immunostained to detect CD31 confirmed significant increases in distal flap vessel count and vascular surface area in female compared to male mice (vessel count: female 127 ± 12 vessels/mm2 versus male 38 ± 6 vessels/mm2, p < 0.05; vascular surface area: female 7,899 ± 85 µ2/mm2 versus male 2,335 ± 40 µ2/mm2, p < 0.05).
Conclusions: In a graded-ischemia wound healing model, flap revascularization was more effective in female mice. The recognition and identification of sex-specific wound healing differences may lead to a better understanding of the underlying mechanisms of myocutaneous revascularization and drive novel discovery to improve soft tissue wound healing.