Paraplegia prevention by oral pretreatment with memantine in a rabbit model

• Published in: The Journal of thoracic and cardiovascular surgery Vol. 148; no. 4; pp. 1732 - 1738
• Main Authors: Panthee, Nirmal, MBBS, Ono, Minoru, MD, PhD, Morota, Tetsuro, MD, PhD, Tanaka, Tsuruhito, MD, Itoda, Yoshifumi, MD, PhD, Ikemura, Masako, MD, PhD, Yamamoto, Takehito, PhD, Suzuki, Hiroshi, PhD, Saito, Aya, MD, PhD, Motomura, Noboru, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2014
• Subjects: Administration, Oral; Animals; Aorta, Abdominal; Cardiothoracic Surgery; Constriction; Evoked Potentials, Motor; Memantine - administration & dosage; Memantine - pharmacology; Paraplegia - pathology; Paraplegia - prevention & control; Rabbits; Spinal Cord Ischemia - pathology; Spinal Cord Ischemia - prevention & control; AMPA; 26; N-methyl- d-aspartate; TAAA; α-amino-3-hydroxy-5-methyl-4-isoxazole proprionate; inferior vena cava; motor evoked potential; CSF; cerebrospinal fluid; IVC; NMDA; MEP; thoracoabdominal aortic aneurysm
• ISSN: 0022-5223; 1097-685X
• DOI: 10.1016/j.jtcvs.2014.04.043

Objective To evaluate the role of memantine ( N -methyl- d -aspartate receptor antagonist) pretreatment for the prevention of spinal cord ischemia after infrarenal aortic clamping in a rabbit model. Methods Thirty New Zealand White rabbits were divided into 5 different groups of 6 rabbits. Groups 60-7 and 60-5 received oral memantine 60 mg once a day for 7 and 5 days, respectively, and groups 30-5 and 30-3 received oral memantine 30 mg once a day for 5 and 3 days, respectively, all before surgery. Group C (control) received normal feeds without memantine. A paraplegic model was created by clamping both the aorta and the inferior vena cava infrarenally and just proximal to their bifurcations for 45 minutes. The modified Tarlov score, motor evoked potential (MEP), serum memantine concentration, and histopathology of the spinal cord were evaluated. Results The mean modified Tarlov scores were 4.2 ± 1.3, 4.3 ± 1.0, 4.2 ± 1.3, 4.3 ± 1.2, and 0.8 ± 1.6 in groups 60-7, 60-5, 30-5, 30-3, and C, respectively at 6, 24, 48, and 72 hours ( P  < .009 for individual groups vs control). Percentage amplitude loss of MEP by the end of surgery was 29.5% ± 46.3%, 11.9% ± 28.0%, 30.0% ± 46.8%, 16.7% ± 40.8%, and 81.8% ± 40.3% for the 5 groups, respectively ( P  = .049). After declamping, MEP reappeared in 83%, 100%, 83%, 83%, and 33% of cases in the 5 groups, respectively ( P  = .073). The serum memantine level was similar in the 4 memantine groups. Spinal cords were normal in most of the rabbits in groups 60-7, 60-5, 30-5, and 30-3, but severely ischemic in most of the rabbits in group C ( P  = .041). Conclusions Oral memantine pretreatment is protective against spinal cord ischemia, and can be an additional strategy for the prevention of paraplegia during thoracoabdominal aortic surgeries.