Combination therapy for salvaging a failing, experimental skin flap
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Updated: Nov 4, 2026
Murine Full-thickness Skin Transplantation
Published on: January 2, 2017
D K Shah1, W X Zhang, D L Forman
1Department of Otolaryngology, Head and Neck Surgery, Mount Sinai Medical Center, New York, New York 10029, USA.
Abstract:
The failing free flap remains a major problem for the reconstructive surgeon. Many and varied pharmacologic agents have been utilized to reverse the effects of ischemia in these flaps. Treatments have been aimed at inhibiting presumed causative factors in the no-reflow phenomenon. Therapy has generally been single in nature and designed to affect only one of these presumed factors. In this study, several pharmacologic agents were utilized individually or in combination therapy as postischemic washouts, in an effort to attack the multiple causative factors in the no-reflow phenomenon and to improve flap survival in a rat abdominal skin flap model. The treatment agents included lactated Ringer's, superoxide dismutase, and urokinase, with each used independently as a postischemic perfusion washout. Combination therapy utilized an initial postischemic perfusion with urokinase, followed by a second perfusion washout with superoxide dismutase. After 18 hr of primary ischemia, there was increased flap survival in the animals undergoing perfusion washout with either superoxide dismutase alone or with combined urokinase and superoxide dismutase washouts, compared to all other treatments (p < 0.001). It was found that flaps undergoing combined urokinase and superoxide dismutase postischemic perfusion washouts demonstrated significantly improved survival after 20 hr of primary ischemia, compared to all other therapies (p < 0.05). By demonstrating improved survival when a thrombolytic agent is used in conjunction with an oxygen free radical scavenger, these findings may have implications in the treatment of clinically failing free flaps.
Insights
Combination therapy using urokinase and superoxide dismutase significantly improved free flap survival in a rat model. This approach targets multiple factors contributing to ischemia-reperfusion injury, offering potential for clinical applications in reconstructive surgery.
Area of Science:
- Reconstructive Surgery
- Ischemia-Reperfusion Injury
- Pharmacologic Interventions
Background:
- Failing free flaps are a significant challenge in reconstructive surgery.
- Existing treatments often address single factors of the no-reflow phenomenon.
- The no-reflow phenomenon, a consequence of ischemia, impairs flap survival.
Purpose of the Study:
- To evaluate the efficacy of individual and combination pharmacologic agents as postischemic perfusion washouts.
- To improve free flap survival by addressing multiple causative factors of the no-reflow phenomenon.
- To investigate the impact of superoxide dismutase and urokinase in a rat abdominal skin flap model.
Main Methods:
- Utilized a rat abdominal skin flap model to simulate free flap ischemia.
- Administered postischemic perfusion washouts with lactated Ringer's, superoxide dismutase, and urokinase individually.
- Implemented combination therapy with urokinase followed by superoxide dismutase washout.
Main Results:
- Superoxide dismutase alone and combined urokinase/superoxide dismutase washouts increased flap survival after 18 hours of ischemia (p < 0.001).
- Combined urokinase and superoxide dismutase washouts significantly improved flap survival after 20 hours of ischemia (p < 0.05).
- Combination therapy demonstrated superior outcomes compared to single-agent treatments.
Conclusions:
- Combining a thrombolytic agent (urokinase) with an oxygen free radical scavenger (superoxide dismutase) enhances postischemic free flap survival.
- This multi-targeted approach holds promise for treating clinically failing free flaps.
- The findings suggest a novel therapeutic strategy for mitigating ischemia-reperfusion injury in reconstructive surgery.
