PURPOSE: This study was undertaken to evaluate whether neurologic outcome after aortic cross-clamping in rabbits could be improved with perioperative infusion of the hydroxyl radical scavenger dimethylthiourea and, if so, to determine whether it is effective during the period of ischemia, reperfusion, or both. METHODS: In 41 New Zealand White rabbits, a snare occlusion device was placed at operation around the infrarenal aorta and tunneled into a subcutaneous position. Animals were then allowed to recover and, 48 hours later, randomized into four groups. In each group, the infrarenal aorta was occluded by tightening the snare in the awake animal. In groups 1, 2, and 3, cross-clamp time was 21 minutes. Group 1 (control) animals received saline solution, whereas group 2 (preclamp 21) received dimethylthiourea 750 mg/kg intravenously just before aortic clamping. In group 3 (prerep 21), dimethylthiourea was given just before reperfusion. Group 4 received dimethylthiourea before clamping, with cross-clamp time extended to 31 minutes. A second dose of saline solution or dimethylthiourea was given 12 hours after clamping in controls and the three treatment groups, respectively. Animals were observed for 5 days, and final neurologic recovery was graded by an independent observer. Animals were then killed, and their spinal cords were removed for histologic examination. RESULTS: Complete paraplegia and marked histologic spinal cord injury at 5 days were seen in 91% (10/11) of group 1 (control) animals, whereas all animals in group 2 (preclamp 21) showed neurologic recovery (p < 0.0001). In group 3 (prerep 21), the final paraplegia rate was 50% (5 of 10), in group 4 (preclamp 31), 100% (10 of 10). CONCLUSIONS: Our results suggest that hydroxyl radicals play an important role in ischemia-reperfusion injury of the spinal cord and that treatment with dimethylthiourea can prevent paraplegia after 21 minutes of aortic cross-clamping in rabbits.
PURPOSE: This study was undertaken to evaluate whether neurologic outcome after aortic cross-clamping in rabbits could be improved with perioperative infusion of the hydroxyl radical scavenger dimethylthiourea and, if so, to determine whether it is effective during the period of ischemia, reperfusion, or both. METHODS: In 41 New Zealand White rabbits, a snare occlusion device was placed at operation around the infrarenal aorta and tunneled into a subcutaneous position. Animals were then allowed to recover and, 48 hours later, randomized into four groups. In each group, the infrarenal aorta was occluded by tightening the snare in the awake animal. In groups 1, 2, and 3, cross-clamp time was 21 minutes. Group 1 (control) animals received saline solution, whereas group 2 (preclamp 21) received dimethylthiourea 750 mg/kg intravenously just before aortic clamping. In group 3 (prerep 21), dimethylthiourea was given just before reperfusion. Group 4 received dimethylthiourea before clamping, with cross-clamp time extended to 31 minutes. A second dose of saline solution or dimethylthiourea was given 12 hours after clamping in controls and the three treatment groups, respectively. Animals were observed for 5 days, and final neurologic recovery was graded by an independent observer. Animals were then killed, and their spinal cords were removed for histologic examination. RESULTS: Complete paraplegia and marked histologic spinal cord injury at 5 days were seen in 91% (10/11) of group 1 (control) animals, whereas all animals in group 2 (preclamp 21) showed neurologic recovery (p < 0.0001). In group 3 (prerep 21), the final paraplegia rate was 50% (5 of 10), in group 4 (preclamp 31), 100% (10 of 10). CONCLUSIONS: Our results suggest that hydroxyl radicals play an important role in ischemia-reperfusion injury of the spinal cord and that treatment with dimethylthiourea can prevent paraplegia after 21 minutes of aortic cross-clamping in rabbits.
Authors: Cristiano Spadaccio; Francesco Nappi; Federico De Marco; Pietro Sedati; Fraser W H Sutherland; Massimo Chello; Marcella Trombetta; Alberto Rainer Journal: Drug Target Insights Date: 2016-02-28