Pyruvate’s Neuroprotection in the Brain Following Cardiac Arrest-Resuscitation

Introduction: Ischemia and reperfusion as a result of cardiac arrest (CA) imposes detrimental injuries to the brain. Previous studies showed that pyruvate, an antioxidant and a cellular metabolite, was associated with upregulation of cellular defense pathways such as hypoxia induced factor 1α (HIF-1α), erythropoietin (EPO), nuclear factor erythroid 2-related factor (Nrf-2) and downregulation of proteins directly involved with apoptosis. Hypothesis: Pyruvate iv infusion during resuscitation preserves neurons and its supportive cells, and thus fosters post-CA neurocognitive recovery in swine. Methods: Yorkshire swine (25-35 kg; n = 18) were subjected to pacing-induced CA, cardiopulmonary resuscitation (CPR) at approximately 100/min at 10-14 min CA, and transthoracic countershocks to restore sinus rhythm. NaCl or Na-pyruvate was infused iv (0.1 mmol/kg/min) during compressions and the first 60 min recovery. At 4 h reperfusion, brain biopsies were freeze-clamped for biochemical analysis and fixed in 10% formalin for immunohistochemistry. Results: At 4h recovery, pyruvate treatment was correlated with an increase trend in hippocampal and cerebellar HIF-1α, EPO, and heme oxygenase-1 (HO-1), a key player in Nrf-2/HO-1 antioxidant pathway. Pyruvate did not affect brain Nrf-2 content among animals subjected to cardiac arrest. Conclusions: Many cellular pathways may contribute to initial brain injury and protection after CA. Further analyses are being conducted to elucidate pyruvate’s neuroprotection effect on the brain after ischemia-reperfusion by CA. NINDS support: R01 NS076975