The N-methyl-D -aspartate antagonist memantine has no neuroprotective effect during hypothermic circulatory arrest: A study in the chronic porcine model

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The Journal of Thoracic and Cardiovascular Surgery

Discussion The Journal of Thoracic and Cardiovascular Surgery

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The N-methyl-D -aspartate antagonist memantine has no neuroprotective effect during hypothermic circulatory arrest: A study in the chronic porcine model Jussi Rimpiläinen, MDa, Matti Pokela, MSa, Kai Kiviluoma, MD, PhDb, Vilho Vainionpää, MD, PhDb, Jorma Hirvonen, MD, PhDc, Pasi Ohtonen, MSca, Ville Jäntti, MD, PhDd, Vesa Anttila, MDa, Hanna Heinonen, MDd, Tatu Juvonen, MD, PhDa The Journal of Thoracic and Cardiovascular Surgery Volume 121, Issue 5, Pages 957-970 (May 2001) DOI: 10.1067/mtc.2001.112934 Copyright © 2001 American Association for Thoracic Surgery Terms and Conditions

Fig. 1 Epidural temperatures of 20 pigs receiving either memantine (5 mg/kg) or placebo before a 75-minute period of HCA. Values are shown as medians with interquartile ranges. The Journal of Thoracic and Cardiovascular Surgery 2001 121, 957-970DOI: (10.1067/mtc.2001.112934) Copyright © 2001 American Association for Thoracic Surgery Terms and Conditions

Fig. 2 EEG burst recovery of 20 pigs receiving either memantine (5 mg/kg) or placebo before a 75-minute period of HCA. The Journal of Thoracic and Cardiovascular Surgery 2001 121, 957-970DOI: (10.1067/mtc.2001.112934) Copyright © 2001 American Association for Thoracic Surgery Terms and Conditions

Fig. 3 Daily scores indicating behavioral recovery among 20 pigs receiving either memantine (5 mg/kg) or placebo before a 75-minute period of HCA. A score of 8 or 9 indicates essentially complete recovery, lower scores indicate substantial impairment, and 0 indicates coma or death. The Journal of Thoracic and Cardiovascular Surgery 2001 121, 957-970DOI: (10.1067/mtc.2001.112934) Copyright © 2001 American Association for Thoracic Surgery Terms and Conditions

Fig. 4 A, A 7-day-old local necrosis (infarction) in the frontal cortex in a memantine-treated pig. The arrow depicts a zone of new capillaries at the border of the necrosis. In the lesion (center of figure) neurons are not seen and glial cells and macrophages are accumulated in this area. The finding was classified as a third-degree lesion. B, A similar local necrosis as above in the frontal cortex of a control pig. The arrow depicts new capillaries. Gliosis and macrophages are also seen. C, A staining from hippocampus indicates that injured neurons have turned red, but surviving neurons have normal color. Edema is seen around the small vessels. The finding was classified as a first-degree lesion. D, Hemorrhage in medulla oblongata, classified as a second-degree lesion in our scale. A few injured red neurons are seen around the bleeding. (A, B, C, and D, Hematoxylin and eosin stain, original magnification 60×.) The Journal of Thoracic and Cardiovascular Surgery 2001 121, 957-970DOI: (10.1067/mtc.2001.112934) Copyright © 2001 American Association for Thoracic Surgery Terms and Conditions

Fig. 5 Total histopathologic scores among 20 pigs receiving either memantine (5 mg/kg) or placebo before a 75-minute period of HCA. The total histopathologic score was calculated by adding the quantitative assessment of histopathologic findings in the investigated regions of the brain for each of the animals. The Journal of Thoracic and Cardiovascular Surgery 2001 121, 957-970DOI: (10.1067/mtc.2001.112934) Copyright © 2001 American Association for Thoracic Surgery Terms and Conditions

Fig. 6 Intracerebral concentrations of lactate, glycerol, glutamate, and glucose of 20 pigs, either memantine (5 mg/kg) or placebo, before a 75-minute period of HCA. Values are shown as medians. The Journal of Thoracic and Cardiovascular Surgery 2001 121, 957-970DOI: (10.1067/mtc.2001.112934) Copyright © 2001 American Association for Thoracic Surgery Terms and Conditions

Fig. 7 Correlation between glutamate levels and EEG burst recovery 3 hours after the start of rewarming of 20 pigs undergoing a 75-minute period of HCA. The Journal of Thoracic and Cardiovascular Surgery 2001 121, 957-970DOI: (10.1067/mtc.2001.112934) Copyright © 2001 American Association for Thoracic Surgery Terms and Conditions

Fig. 8 Correlation between highest individual glutamate value and histopathologic score of 20 pigs undergoing a 75-minute period of HCA. The Journal of Thoracic and Cardiovascular Surgery 2001 121, 957-970DOI: (10.1067/mtc.2001.112934) Copyright © 2001 American Association for Thoracic Surgery Terms and Conditions