Improvement of Spinal Cord Electrical Activity with Lazaroid (U74006F) During Operations on the Thoracic Aorta: Evaluation of a Novel Lipid Peroxidation Inhibitor

Abstract

Reperfusion injury may contribute to spinal cord damage after cross-clamping of the thoracic aorta (AXC). Tirilazad (U74006F), a potent free radical scavenger and lipid peroxidation inhibitor, has proven to be beneficial in ischemia/reperfusion models. The authors investigated the efficacy of U74006F in preventing paraplegia following forty-five minutes of normothermic AXC distal to the origin of the left subclavian artery. Thirty-two mongrel dogs were assigned to receiving either vehicle as pretreatment (control, n = 7) or 1.5 mg/kg U74006F (group II, n=7) or 3 mg/kg U74006F (group III, n = 10) infused into the descending aorta distal to the clamp for twenty minutes during reperfusion, or 3 mg/kg U74006F IV as pretreatment twenty-five minutes before the onset of ischemia (group IV, n = 8).

Mean proximal (BPpr) and distal (BP_dx) aortic pressures and somatosensory evoked potentials (SEP) were measured at baseline and at minutes 2, 5, 7, 10, 15, 30, and 45 after AXC. SEP and neurologic outcome (Tarlov criteria) were assessed twenty-four hours postprocedure. There was no difference between BP_px or BP _dx and their counterparts in the U74006F-treated animals and the control. SEP returned faster in all treatment groups when compared with controls. However, the neurologic outcome did not differ among groups. The authors conclude that although U74006F did not improve the neurologic outcome, it had a positive effect on the recovery of electrical activity of the spinal cord following transient ischemia. This suggests that the injury to the spinal cord induced by AXC is caused, in part, during reperfusion.