Cereb
ral oxi
dative stress an
d metabolic
dysfunction impe
de neurological recovery from car
diac arrest-resuscitation. Pyruvate, a potent antioxi
dant an
d energy-yiel
ding fuel, has been shown to protect against oxi
dant- an
d ischemia-in
duce
d neuronal
damage. This stu
dy teste
d whether acute pyruvate treatment
during car
diopulmonary resuscitation can prevent neurological
dysfunction an
d cereb
ral injury following car
diac 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.