Pyruvate enhances neurological recovery following cardiopulmonary arrest and resuscitation.

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