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J Thorac Cardiovasc Surg 2001;122:979-985
© 2001 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology (CSP)

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

From the First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Received for publication Dec 14, 2000. Revisions requested Jan 22, 2001; revisions received Feb 6, 2001. Accepted for publication May 16, 2001. Address for reprints: Hitoshi Terada, MD, First Department of Surgery, Hamamatsu University School of Medicine, 3600, Handa-cho, Hamamatsu, 431-3192, Japan (E-mail: terada{at}hama-med.ac.jp).

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.

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