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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.
SUBMITTER: Sharma AB
PROVIDER: S-EPMC2737333 | biostudies-literature | 2008 Jan
REPOSITORIES: biostudies-literature
Resuscitation 20070706 1
<h4>Purpose</h4>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.<h4>Methods</h4>Anesthetized, open-chest mongrel dogs underw ...[more]