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-induced reperfusion injury in the skin and muscle of latissimus dorsi myocutaneous flaps was studied in pigs weighing 19.7 +/- 0.5 kg. The latissimus dorsi myocutaneous flaps were subjected to 4, 6, or 8 hours of warm global ischemia. The length and area of viable and nonviable skin and muscle were assessed 48 hours after the ischemic insult by using the fluorescein and nitroblue tetrazolium dye tests, respectively. It was observed that perioperative deferoxamine treatment (250 mg/kg IV) was effective (p < 0.05) in attenuation of ischemia-induced reperfusion injury in the skin but not in the muscle of latissimus dorsi myocutaneous flaps subjected to 4, 6, or 8 hours (n = 10) of ischemia compared with the saline-treated control (n = 10). In a separate study, it was observed that preoperative deferoxamine treatment (250 mg/kg per day 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 to 4 hours of ischemia and 48 hours of reperfusion (n = 10) compared with the saline treated control (n = 10). Morphologic studies with light and electron microscopy also provided evidence to indicate that preoperative plus perioperative deferoxamine treatment, but not perioperative deferoxamine treatment alone, remarkably reduced ischemia-induced reperfusion injury in the skeletal muscle of latissimus dorsi myocutaneous flaps compared with the saline-treated control. It is concluded that deferoxamine is effective in the attenuation of ischemia-induced reperfusion injury in the skin and muscle of pig latissimus dorsi myocutaneous flaps, but a longer period and/or higher dose of deferoxamine treatment is required for the muscle than for the skin. The pharmacologic actions and metabolism of deferoxamine relating to mitigation of ischemia-induced reperfusion injury in the pig skin and muscle are discussed.
Division of Surgical Research, Hospital for Sick Children, Toronto, Ontario, Canada.
S F
SF
Morris
C Y
CY
Pang
N M
NM
Lofchy
G
G
Davidson
W K
WK
Lindsay
R M
RM
Zuker
B
B
Boyd
D000818:Animals; D001706:Biopsy; D003676:Deferoxamine / Q000627:therapeutic use*; D008297:Male; D008854:Microscopy, Electron; D009132:Muscles / Q000098:blood supply / Q000473:pathology; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D012867:Skin / Q000098:blood supply / Q000473:pathology; D013524:Surgical Flaps / Q000473:pathology*; D013552:Swine
D003676:Deferoxamine