Pyruvate enhances neurological recovery following cardiopulmonary arrest and resuscitation

Arti B. Sharma, Matthew A. Barlow, Shao Hua Yang, James W. Simpkins, Robert T. Mallet

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Purpose: Cerebral oxidative stress and metabolic dysfunction impede neurological recovery from cardiac arrest-resuscitation. Pyruvate, a potent antioxidant and energy-yielding fuel, has been shown to protect against oxidant- and ischemia-induced neuronal damage. This study tested whether acute pyruvate treatment during cardiopulmonary resuscitation can prevent neurological dysfunction and cerebral injury following cardiac arrest. Methods: Anesthetized, open-chest mongrel dogs underwent 5 min cardiac arrest, 5 min open-chest cardiac compression (OCCC), defibrillation and 3-day recovery. Pyruvate (n = 9) or NaCl volume control (n = 8) were given (0.125 mmol kg-1 min-1 i.v.) throughout OCCC and the first 55 min recovery. Sham dogs (n = 6) underwent surgery and recovery without cardiac arrest-resuscitation. Results: Neurological deficit score (NDS), evaluated at 2-day recovery, was sharply increased in NaCl-treated dogs (10.3 ± 3.5) versus shams (1.2 ± 0.4), but pyruvate treatment mitigated neurological deficit (NDS = 3.3 ± 1.2; P < 0.05 versus NaCl). Brain samples were taken for histological examination and evaluation of inflammation and cell death at 3-day recovery. Loss of pyramidal neurons in the hippocampal CA1 subregion was greater in the NaCl controls than in pyruvate-treated dogs (11.7 ± 2.3% versus 4.3 ± 1.2%; P < 0.05). Cardiac arrest increased caspase-3 activity, matrix metalloproteinase activity, and DNA fragmentation in the CA1 subregion; pyruvate prevented caspase-3 activation and DNA fragmentation, and suppressed matrix metalloproteinase activity. Conclusion: Intravenous pyruvate therapy during cardiopulmonary resuscitation prevents initial oxidative stress and neuronal injury and enhances neurological recovery from cardiac arrest.

Original languageEnglish
Pages (from-to)108-119
Number of pages12
JournalResuscitation
Volume76
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • Brain ischemia
  • Cardiac arrest
  • Cardiopulmonary resuscitation (CPR)
  • Cerebral blood flow
  • Inflammatory response
  • Metabolism
  • Neurological dysfunction
  • Post-resuscitation period

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