Published in:
01-11-2020 | Motor Evoked Potential | Original Article
Evaluation of spinal cord protective threshold of serum memantine, an NMDA receptor antagonist, in a rabbit model of paraplegia
Published in: Indian Journal of Thoracic and Cardiovascular Surgery | Issue 6/2020
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Purpose
To evaluate the threshold of serum memantine for prevention of spinal cord injury (SCI) in a rabbit paraplegic model.
Methods
Forty-two New Zealand white rabbits were divided into 7 groups. Preoperatively, oral memantine was given starting from 60 mg OD for 7 days in the initial group, then reducing the dose and/or duration to 60 mg OD for 5 days, 30 mg OD for 5 days, 30 mg OD for 3 days, 15 mg OD for 3 days, 30 mg single dose, and 60 mg single dose, in subsequent 6 groups. A paraplegic model was created by clamping both infrarenal aorta and inferior vena cava (IVC) for 45 min. Motor evoked potentials (MEPs), modified Tarlov score (0–5), serum memantine concentration, and histopathology of the spinal cord were evaluated.
Results
Half of all rabbits (21/42) showed spinal protection. Receiver operating characteristic (ROC) curve analysis showed serum level of 4.5 ng/ml as a cutoff value for spinal protection (sensitivity 86%, specificity 62%, area under the curve (AUC) 0.785, P = .002). Sixteen rabbits had serum level ≥ 4.5 ng/ml (group A), with 26 rabbits having < 4.5 ng/ml (group B). Further comparison was done between groups A and B. The mean modified Tarlov score at 6, 24, 48, and 72 h was 4.5 ± 0.9 and 2.4 ± 1.6, in groups A and B, respectively (P < .001). The modified Tarlov score showed positive correlation with serum memantine level (Spearman’s rho = 0.618, P = .01). Results of MEP and histopathology were significantly better for group A.
Conclusions
We showed that memantine is protective against SCI at serum levels ≥ 4.5 ng/ml in a rabbit model; thus, it can be a potential adjunct for spinal protection during thoracic/thoracoabdominal aortic surgeries.