Caspase inhibition enhances ischemic tolerance of fasciocutaneous flaps

Baran D. Sumer, Brian R. Gastman, Feng Gao, Bruce H. Haughey, Randal C. Paniello, Brian Nussenbaum

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1358-1361
Number of pages4
JournalLaryngoscope
Volume115
Issue number8
DOIs
StatePublished - Aug 2005

Fingerprint

Caspases
Ischemia
Dimethyl Sulfoxide
Caspase Inhibitors
Confidence Intervals
Reperfusion Injury
Apoptosis
Free Radical Scavengers
Intraperitoneal Injections
Reperfusion
Sprague Dawley Rats

Keywords

  • Apoptosis
  • Caspases
  • Dimethylsulfoxide
  • Epigastric flap
  • Ischemia time

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Sumer, B. D., Gastman, B. R., Gao, F., Haughey, B. H., Paniello, R. C., & Nussenbaum, B. (2005). Caspase inhibition enhances ischemic tolerance of fasciocutaneous flaps. Laryngoscope, 115(8), 1358-1361. https://doi.org/10.1097/01.MLG.0000166696.68815.C8

Caspase inhibition enhances ischemic tolerance of fasciocutaneous flaps. / Sumer, Baran D.; Gastman, Brian R.; Gao, Feng; Haughey, Bruce H.; Paniello, Randal C.; Nussenbaum, Brian.

In: Laryngoscope, Vol. 115, No. 8, 08.2005, p. 1358-1361.

Research output: Contribution to journalArticle

Sumer, BD, Gastman, BR, Gao, F, Haughey, BH, Paniello, RC & Nussenbaum, B 2005, 'Caspase inhibition enhances ischemic tolerance of fasciocutaneous flaps', Laryngoscope, vol. 115, no. 8, pp. 1358-1361. https://doi.org/10.1097/01.MLG.0000166696.68815.C8
Sumer, Baran D. ; Gastman, Brian R. ; Gao, Feng ; Haughey, Bruce H. ; Paniello, Randal C. ; Nussenbaum, Brian. / Caspase inhibition enhances ischemic tolerance of fasciocutaneous flaps. In: Laryngoscope. 2005 ; Vol. 115, No. 8. pp. 1358-1361.
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AU - Sumer, Baran D.

AU - Gastman, Brian R.

AU - Gao, Feng

AU - Haughey, Bruce H.

AU - Paniello, Randal C.

AU - Nussenbaum, Brian

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N2 - 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.

AB - 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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KW - Dimethylsulfoxide

KW - Epigastric flap

KW - Ischemia time

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