EFFECTS OF 21-AMINOSTEROID U74389F ON SKIN-FLAP SURVIVAL AFTER SECONDARY ISCHEMIA

The effect of 21-aminosteroid, a lazaroid (U74389F), on tissue injury after secondary ischemia was evaluated in 3 x 5 cm island skin flaps i n male Sprague-Dawley rats (n = 30). Primary ischemia was produced by arteriovenous occlusion for 1 hour. Eighteen hours later, secondary is chemia was inflicted by 4-hour venous occlusion. The treatment group r eceived intravenous lazaroid (3 mg/kg) 30 minutes before the start of secondary ischemia. The control group received the same volume of citr ate buffer vehicle using the same route and schedule. Skin-flap surviv al was an all-or-none phenomenon and assessed at 7 days after secondar y ischemia. Malondialdehyde (MDA) content was measured to determine th e occurrence of lipid peroxidation. Myeloperoxidase (MPO) activity was assayed to assess the degree of neutrophil infiltration. Treatment wi th this lazaroid significantly improved the survival rate from 0 perce nt (0 of 13) to 53 percent (9 of 17) (p < 0.01). Malondialdehyde conte nt was 62 +/- 10 (mean +/- SEM, n = 4) pmol/mg dry weight in normal sk in. Malondialdehyde increased by 3 times normal in the flaps destined to survive and by 13 times in the flaps destined to undergo necrosis ( p < 0.001). Myeloperoxidase activity was negligible in normal skin. At the end of secondary ischemia, the flaps destined to survive exhibite d a high myeloperoxidase activity. The flaps destined to necrosis show ed the enzyme activity 2.2 times more than surviving flaps (p < 0.01). The results suggest that the lazaroid U74389F may improve survival by attenuating neutrophil infiltration and by reducing lipid peroxidatio n.