AMPA glutamate receptor antagonism reduces neurologic injury after hypothermic circulatory arrest

J. Mark Redmond, Kenton J Zehr, Mary E Blue, Mary S. Lange, A. Marc Gillinov, Juan C Troncoso, Duke E. Cameron, Michael V Johnston, William A Baumgartner

Research output: Contribution to journalArticle

Abstract

Pharmacologic inhibition of the N-methyl-d-aspartate (NMDA) glutamate receptor can reduce the neurologic injury associated with hypothermic circulatory arrest; however, other receptor subtypes, such as the α-amino-3-hydroxy-5-methylisoazole-4-propionic acid/kainate or AMPA/kainate subtype, may predominate in the adult brain. In this experiment, a selective AMPA antagonist, NBQX, was used in a canine survival model of hypothermic circulatory arrest. Twelve male dogs (20 to 25 kg) were placed on closed-chest cardiopulmonary bypass, subjected to 2 hours of hypothermic circulatory arrest at 18°C, and rewarmed on cardiopulmonary bypass. All were mechanically ventilated and monitored for 20 hours before extubation and survived for 3 days. Six dogs received NBQX beginning 2 hours after arrest (3 mg/kg for 3 hours then 1.5 mg/kg for 2 hours). Control dogs received vehicle only. Neurologic recovery was assessed every 12 hours using a species-specific behavior scale that yielded a neurodeficit score ranging from 0 (normal) to 500 (brain dead). After sacrifice at 72 hours, brains were examined by receptor autoradiography and histologically for patterns of selective neuronal necrosis and scored blindly from 0 (normal) to 100 (severe injury). Dogs given NBQX had better neurologic function compared with controls (neurodeficit score, 58.6 ± 15 versus 204 ± 30; p <0.004) and had less neuronal injury (18.2 ± 3 versus 52.5 ± 6; p <0.004). Densitometric receptor autoradiography revealed preservation of neuronal NMDA receptor expression only in dogs given NBQX. These results suggest that antagonism of the non-NMDA glutamate receptor AMPA may be neuroprotective in adults after hypothermic circulatory arrest.

Original languageEnglish (US)
Pages (from-to)579-584
Number of pages6
JournalAnnals of Thoracic Surgery
Volume59
Issue number3
DOIs
StatePublished - 1995

Fingerprint

Nervous System Trauma
AMPA Receptors
Glutamate Receptors
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Dogs
Kainic Acid
Autoradiography
Cardiopulmonary Bypass
Nervous System
Brain Death
Wounds and Injuries
Brain
Canidae
Necrosis
Thorax
2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
aspartic acid receptor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery

Cite this

AMPA glutamate receptor antagonism reduces neurologic injury after hypothermic circulatory arrest. / Mark Redmond, J.; Zehr, Kenton J; Blue, Mary E; Lange, Mary S.; Marc Gillinov, A.; Troncoso, Juan C; Cameron, Duke E.; Johnston, Michael V; Baumgartner, William A.

In: Annals of Thoracic Surgery, Vol. 59, No. 3, 1995, p. 579-584.

Research output: Contribution to journalArticle

Mark Redmond, J. ; Zehr, Kenton J ; Blue, Mary E ; Lange, Mary S. ; Marc Gillinov, A. ; Troncoso, Juan C ; Cameron, Duke E. ; Johnston, Michael V ; Baumgartner, William A. / AMPA glutamate receptor antagonism reduces neurologic injury after hypothermic circulatory arrest. In: Annals of Thoracic Surgery. 1995 ; Vol. 59, No. 3. pp. 579-584.
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