Increased intracerebral excitatory amino acids and nitric oxide after hypothermic circulatory arrest

Elaine E. Tseng, Malcolm V Brock, Christopher C. Kwon, Madhu Annanata, Mary S. Lange, Juan C Troncoso, Michael V Johnston, William A Baumgartner

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Abstract

Background. Prolonged hypothermic circulatory arrest (HCA) results in neurologic injury, but the mechanism of this injury is unknown. This study was undertaken to measure quantitatively intracerebral excitatory amino acids and citrulline, an equal coproduct of nitric oxide, during HCA. We hypothesized that HCA resulted in higher levels of glutamate, aspartate, glycine, causing increased intracellular calcium, and therefore, nitric oxide and citrulline. Methods. Ten dogs underwent intracerebral microdialysis and 2 hours of HCA at 18°C. Effluent was analyzed by high performance liquid chromatography with electrochemical detection. Five clogs each were sacrificed at 8 and 20 hours after HCA. Neuronal apoptosis was scored from 0 (no injury) to 100 (severe injury). Results. Time course of HCA was divided into six periods. Peak levels of amino acids in each period were compared with those at baseline. Glutamate, coagonist glycine, and citrulline, an equal coproduct of nitric oxide, increased significantly over baseline during HCA, cardiopulmonary bypass, and 2 to 8 hours after HCA. Aspartate increased significantly during HCA and 8 to 20 hours after HCA. Apoptosis score was 65.56 ± 5.67 at 8 hours and 30.63 ± 14.96 at 20 hours after HCA. Conclusions. Our results provide direct evidence that HCA causes increased intracerebral glutamate and aspartate, along with coagonist glycine. We conclude that HCA causes glutamate excitotoxicity with subsequent nitric oxide production resulting in neurologic injury, which begins during arrest and continues until 20 hours after hypothermic circulation arrest. To provide effective cerebral protection, pharmacologic strategies to reduce glutamate excitotoxicity require intervention beyond the initial ischemic insult.

Original languageEnglish (US)
Pages (from-to)371-376
Number of pages6
JournalAnnals of Thoracic Surgery
Volume67
Issue number2
DOIs
Publication statusPublished - Feb 1999

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

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