Effects of the lazaroid U74389G (21 aminosteroid) on skeletal muscle reperfusion injury in rabbits

The purpose of this experiment was to evaluate the effects of the aminosteroid U74389G on skeletal muscle reperfusion injury in rabbits. In 24 white New Zealand rabbits (weighing 7.0-8.0 lb), the rectus femoris muscle on both sides was completely isolated on a single vascular pedicle (artery and vein) and a major accessory vein. All muscles were weighed using a suspension spring balance and then underwent 4 hours of normothermic ischemia followed by 24 hours of reperfusion. Muscle ischemia was induced by the application of atraumatic vascular clamps to the vascular pedicles. Complete muscle ischemia and reperfusion were documented by a laser flow meter. The animals were divided into three groups; Group I (n = 8) served as control, Group II (n = 8) received an IV bolus of U74389G (1.5 mg/kg) five minutes prior to ischemia, Group III (n = 8) was given the same dose of lazaroid five minutes prior to reperfusion. Muscle biopsies were obtained before ischemia and after reperfusion for quantification of myeloperoxidase (MPO) activity. At the completion of reperfusion, the muscles were excised, weighed and cut into slices along the longitudinal axis and then incubated for 30 minutes in 0.05% nitroblue tetrazolium. Areas of necrosis were determined by computerized planimetry. The following results indicate that reperfusion muscle necrosis in rabbits is significantly decreased by the administration of the lazaroid U74389G. Leukocyte sequestration was not affected by the lazaroid administration. These beneficial effects were observed whether the lazaroid was administered prior to ischemia or prior to reperfusion and were independent of leukocyte sequestration.