Reduction of ischemic spinal cord injury by dextrorphan: comparison of several methods of administration

Abstract

Objectives: We investigated the effect of dextrorphan, an N -methyl-D -aspartate receptor antagonist, on the reduction of ischemic spinal cord injury and the safe clamping time after various methods of administration.

Methods: Spinal cord ischemia was induced in New Zealand White rabbits by infrarenal aortic clamping and animals were divided into 5 groups. Group A (n = 15) received simple clamping. Groups B (n = 20) and C (n = 35) received dextrorphan pretreatment (10 mg/kg), followed by continuous intravenous or intra-aortic infusion (1 mg/min), respectively. Group D (n = 25) received the same dextrorphan pretreatment and bolus intra-aortic injection at clamping (1 mg per minute of clamping time). Group E (n = 15) received bolus intrathecal injection of dextrorphan (0.2 mg/kg). Each dextrorphan-treated group had a small group of control animals (n = 5). The neurologic status was assessed by the Johnson score (5 = normal, 0 = paraplegic) 48 hours after unclamping, and animals were put to death for histopathologic examination.

Results: All dextrorphan-treated groups showed better neurologic function than the respective control animals (P <.001 vs groups B, C, and D; P =.014 vs group E). The order of efficacy of dextrorphan (as revealed by the average of neurologic status) was as follows: group C > group D (P =.017, after 50 minutes of clamping), group D > group B (P =.014, after 45 minutes of clamping), and group B > group E (P <.001, after 40 minutes of clamping). Histopathologic findings did not necessarily correspond with hind-limb neurologic function.

Conclusions: Dextrorphan reduced the physical findings associated with ischemic spinal cord injury, and continuous intra-aortic infusion prolonged the safe clamping time significantly more than delivery by other routes.