Evaluation of spinal cord protective threshold of serum memantine, an NMDA receptor antagonist, in a rabbit model of par
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ORIGINAL ARTICLE
Evaluation of spinal cord protective threshold of serum memantine, an NMDA receptor antagonist, in a rabbit model of paraplegia Nirmal Panthee 1 & Minoru Ono 1 Hiroshi Suzuki 2
&
Takehito Yamamoto 2 & Masako Ikemura 3 & Tsuruhito Tanaka 1 & Yoshifumi Itoda 1 &
Received: 14 May 2020 / Revised: 21 July 2020 / Accepted: 28 July 2020 # Indian Association of Cardiovascular-Thoracic Surgeons 2020
Abstract 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. Keywords Spinal cord injury . Memantine . Serum level . Thoracic/thoracoabdominal aortic surgeries
Introduction Spinal cord injury (paraplegia/paraparesis) following thoracoabdominal aortic aneurysm (TAAA) repair is a grave complication, with reported incidence ranging from 2 to 32% [1–8]. The higher incidence corresponds to complex repairs (Crawford I and II) in high-risk patients [3]. Compromised
* Minoru Ono [email protected] 1
Department of Cardiac Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
2
Department of Pharmacy, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
3
Department of Neuropathology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
spinal cord perfusion during aortic clamping is unavoidable, therefore, posing a risk of spinal cord injury during TAAA surgery. Other contributing factors for spinal cord injury include failure to
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