Aprotinin reduces injury of the spinal cord in transient ischemia

OBJECTIVE: The protective effect of aprotinin, which is a protease inhibitor, was assessed in a rabbit spinal cord ischemia model. DESIGN: Randomized, controlled, prospective study. SETTING: University research laboratory. SUBJECTS: New Zealand white rabbits (36) of both sexes. METHODS: In 24 animals, ischemia was induced with midline laparotomy and clamping the aorta just distal to left renal artery and proximal to aortic bifurcation for 20 min. Aprotinin was given 30000 KIU as a short intravenous injection after anesthesia, and was followed by 10000 KIU/h by continuous infusion in group 1 (n = 12). Similar volume of saline solution was used in control group of animals (group 2, n = 12). Group 3 of animals (sham group, n = 12) were anesthetized and subjected to laparotomy without aortic occlusion. Physiological parameters and somatosensory evoked-potentials (SEP) were monitored in animals before ischemia, during ischemia and in the first 60 min of reperfusion. Their neurological outcome was clinically evaluated up to 48 h postischemia. Their motor function was scored, and the intergroup differences were compared. The animals were sacrificed after two days of postischemia. Their spinal cord, abdominal aorta, and its branches were processed for histopathological examination. RESULTS: In group 3, SEP amplitudes did not change during the procedures, and all animals recovered without neurologic deficits. At the end of ischemic period, the average amplitude was reduced to 53+/-7% of the baseline in all ischemic animals. This was followed by a gradual return to 89+/-8 and 81+/-13% of the initial amplitude after 60 min of reperfusion in group 1 and group 2 correspondingly (P > 0.05). The average motor function score was significantly higher in group 1 than group 2 at 24 and 48 h after the ischemic insult (P < 0.05). Histological observations were clearly correlated with the neurological findings. CONCLUSION: The results suggest that aprotinin reduces spinal cord injury and preserves neurologic function in transient spinal cord ischemia in rabbits.