Caspase Inhibition Enhances Ischemic Tolerance of Fasciocutaneous Flaps

Authors

  • Baran D. Sumer MD,

    1. Department of Otolaryngology—Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri
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  • Brian R. Gastman MD,

    1. Department of Plastic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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  • Feng Gao PhD,

    1. Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, U.S.A.
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  • Bruce H. Haughey MBChB,

    1. Department of Otolaryngology—Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri
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  • Randal C. Paniello MD,

    1. Department of Otolaryngology—Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri
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  • Brian Nussenbaum MD

    Corresponding author
    1. Department of Otolaryngology—Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri
    • Dr. Brian Nussenbaum, Department of Otolaryngology—Head and Neck Surgery, Washington University School of Medicine, 660 South Euclid Ave., Campus Box 8115, St. Louis, MO 63110, U.S.A.
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  • Received Second Prize, Francis Lederer Award, Middle Section Meeting of the Triological Society, January 22, 2005.

    This work was supported by internal funds from the Department of Otolaryngology—Head and Neck Surgery at Washington University School of Medicine.

Abstract

Objectives/Hypothesis: To demonstrate the significance of apoptosis in ischemia-reperfusion injury in revascularized fasciocutaneous flaps and test the hypothesis that pharmacologic inhibition of caspases prolongs the allowable primary ischemia time of these flaps.

Study Design: Animal study using the epigastric flap in adult male Sprague-Dawley rats.

Methods: Fifty-nine rats were treated with the caspase inhibitor (Q-VD-OPH) reconstituted in dimethylsulfoxide (DMSO) (n = 20, 8 mg/kg:0.8 mL/kg), DMSO alone (n = 19, 0.8 mL/kg), or saline (n = 20, 0.8 mL/kg). Treatment was given as a single intraperitoneal injection 30 minutes before starting primary ischemia. Epigastric flaps were subjected to increasing ischemia times followed by reperfusion. The flaps were harvested and analyzed 7 days later, and viability was assessed. Probit statistical analysis was used to determine the critical ischemia time. This was defined as the time point when 50% of the flaps in each group were expected to survive.

Results: The calculated critical ischemia times were 8.92 hours (95% confidence interval 7.19–10.47 h) for the saline group, 16.35 hours (95% confidence interval 11.82–19.89 h) for the DMSO group, and 21.73 hours (95% confidence interval 19.39–25.37 h) for the DMSO with Q-VD-OPH group. These differences were significantly different from each other.

Conclusions: Pretreatment of fasciocutaneous flaps with a free radical scavenger alone or in combination with a caspase inhibitor significantly increases the flap's tolerance of primary ischemia. The added benefit of the caspase inhibitor suggests that apoptosis plays an important role in ischemia-reperfusion injury in soft tissue flaps.

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