DEFEROXAMINE ATTENUATES ISCHEMIA-INDUCED REPERFUSION INJURY IN THE SKIN AND MUSCLE OF MYOCUTANEOUS FLAPS IN THE PIG

The dose effect of deferoxamine treatment in attenuation of ischemia-i nduced reperfusion injury in the skin and muscle of latissimus dorsi m yocutaneous flaps was studied in pigs weighing 19.7 +/- 0.5 kg. The la tissimus dorsi myocutaneous flaps were subjected to 4, 6, or 8 hours o f warm global ischemia. The length and area of viable and nonviable sk in and muscle were assessed 48 hours after the ischemic insult by usin g the fluorescein and nitroblue tetrazolium dye tests, respectively. I t was observed that perioperative deferoxamine treatment (250 mg/kg IV ) was effective (p < 0.05) in attenuation of ischemia-induced reperfus ion injury in the skin but not in the muscle of latissimus dorsi myocu taneous flaps subjected to 4, 6, or 8 hours (n = 10) of ischemia compa red with the saline-treated control (n = 10). In a separate study, it was observed that preoperative deferoxamine treatment (250 mg/kg per d ay X 2 days, IM) plus perioperative deferoxamine treatment (250 mg/kg IV) was effective (p < 0.05) in attenuation of muscle ischemia-induced reperfusion injury in latissimus dorsi myocutaneous flaps subjected t o 4 hours of ischemia and 48 hours of reperfusion (n = 10) compared wi th the saline-treated control (n = 10). Morphologic studies with light and electron microscopy also provided evidence to indicate that preop erative plus perioperative deferoxamine treatment, but not perioperati ve deferoxamine treatment alone, remarkably reduced ischemia-induced r eperfusion injury in the skeletal muscle of latissimus dorsi myocutane ous flaps compared with the saline-treated control. It is concluded th at deferoxamine is effective in the attenuation of ischemia-induced re perfusion injury in the skin and muscle of pig latissimus dorsi myocut aneous flaps, but a longer period and/or higher dose of deferoxamine t reatment is required for the muscle than for the skin. The pharmacolog ic actions and metabolism of deferoxamine relating to mitigation of is chemia-induced reperfusion injury in the pig skin and muscle are discu ssed.