Reduction of ischemic spinal cord injury by dextrorphan: comparison of several methods of administration.
OBJECTIVE
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.
Terada
H
H
First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan. terada@hama-med.ac.jp
Kazui
T
T
Takinami
M
M
Yamashita
K
K
Washiyama
N
N
Muhammad
B A
BA
D000818:Animals; D001012:Aorta, Abdominal; D003250:Constriction; D003917:Dextrorphan / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D010264:Paraplegia / Q000517:prevention & control*; D011817:Rabbits; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D020760:Spinal Cord Ischemia / Q000517:prevention & control*; D013997:Time Factors
D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D003917:Dextrorphan