TY - JOUR
T1 - Sex differences in murine myocutaneous flap revascularization
AU - Brandenburg, Jacquelyn S.
AU - Clark, Ross M.
AU - Coffman, Brittany
AU - Sharma, Geetanjali
AU - Hathaway, Helen J.
AU - Prossnitz, Eric R.
AU - Howdieshell, Thomas R.
N1 - Funding Information:
NIH grants: UNM Comprehensive Cancer Center, Grant/Award Number: P30 CA118100; Center of Biomedical Research Excellence in Autophagy, Inflammation, and Metabolism, Grant/Award Number: P20 GM121176; RO1 grants, Grant/Award Numbers: CA163890, CA194496; University of New Mexico Department of Surgery grant (TRH) Funding information
Funding Information:
The authors thank Susan Tigert, research technician of the University of New Mexico Clinical and Translational Science Center (UL1 TR001449) T‐laboratory for technical assistance. The authors were supported by a grant from the University of New Mexico Department of Surgeryt (TRH), the Center of Biomedical Research Excellence in Autophagy, Inflammation, and Metabolism (P20 GM121176), the UNM Comprehensive Cancer Center (P30 CA118100), and NIH R01 grants (CA163890 and CA194496, ERP).
Funding Information:
The authors thank Susan Tigert, research technician of the University of New Mexico Clinical and Translational Science Center (UL1 TR001449) T-laboratory for technical assistance. The authors were supported by a grant from the University of New Mexico Department of Surgeryt (TRH), the Center of Biomedical Research Excellence in Autophagy, Inflammation, and Metabolism (P20 GM121176), the UNM Comprehensive Cancer Center (P30 CA118100), and NIH R01 grants (CA163890 and CA194496, ERP).
Publisher Copyright:
© 2020 by the Wound Healing Society
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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 myocutaneous ischemia/reperfusion. To explore sex differences in wound revascularization, we utilized a murine myocutaneous flap model of graded ischemia. A cranial-based, peninsular-shaped, myocutaneous flap was surgically created on the dorsum of male and female mice. Physiological, pathological, immunohistochemical, and molecular parameters were analyzed. Flaps created on female mice were re-attached 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. Over the 10 day study interval, laser speckle imaging documented functional revascularization in all flap regions in female mice, but minimal distal flap reperfusion in male mice. Day 10 immunostained histologic sections confirmed significant increases in distal flap vessel count and vascular surface area in female compared to male mice. RT-PCR demonstrated significant differences in growth factor and metabolic gene expression between female and male mice at day 10. In conclusion, 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 following tissue transfer for traumatic injury and cancer resection.
AB - 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 myocutaneous ischemia/reperfusion. To explore sex differences in wound revascularization, we utilized a murine myocutaneous flap model of graded ischemia. A cranial-based, peninsular-shaped, myocutaneous flap was surgically created on the dorsum of male and female mice. Physiological, pathological, immunohistochemical, and molecular parameters were analyzed. Flaps created on female mice were re-attached 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. Over the 10 day study interval, laser speckle imaging documented functional revascularization in all flap regions in female mice, but minimal distal flap reperfusion in male mice. Day 10 immunostained histologic sections confirmed significant increases in distal flap vessel count and vascular surface area in female compared to male mice. RT-PCR demonstrated significant differences in growth factor and metabolic gene expression between female and male mice at day 10. In conclusion, 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 following tissue transfer for traumatic injury and cancer resection.
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U2 - 10.1111/wrr.12812
DO - 10.1111/wrr.12812
M3 - Article
C2 - 32428975
AN - SCOPUS:85085018631
SN - 1067-1927
VL - 28
SP - 470
EP - 479
JO - Wound Repair and Regeneration
JF - Wound Repair and Regeneration
IS - 4
ER -