Abstract 2645: Magnesium Sulfate Administered During Cardiopulmonary Resuscitation and Early Post-resuscitation Phase Improves Cerebral Perfusion and Neurological Outcomes via Akt-eNOS Signaling
Background: Cerebral perfusion is usually compromised after cardiopulmonary resuscitation (CPR), which inevitably prolongs ischemic injury of the brain and worsens neurological outcomes. Magnesium sulfate (MgSO4) has long been used during CPR. Magnesium has also been shown to cause vasodilatation. We therefore investigate the roles of MgSO4 on cerebral perfusion during CPR and early post-resuscitation phase, and its prognostic implications in survival and neurological outcomes.
Methods: Using a rat model of asphyxia cardiac arrest (6 min) and CPR, we administered MgSO4 during CPR (50 mg/kg) and/or the first 2 h post-resuscitation (50 mg/kg/hr). The blood pressure was continuously monitored, with cerebral tissue perfusion measured by OxyFLO detector. The brain was harvested 2 h after CPR. Bax, Bcl-2, and phosphorylation of Akt and endothelium-derived nitric oxide synthase (eNOS) were assessed. In a subgroup with minimal invasive procedures, the survival and neurological outcomes were followed up to 3 days.
Results: Cerebral perfusion was significantly reduced after CPR in the control group. MgSO4 (50 mg/kg) given just during CPR enhanced cerebral perfusion only transiently. If MgSO4 infusion (50 mg/kg/hr) was continued through the first 2 h post-resuscitation, the cerebral perfusion was increased and maintained (P<0.01 vs. control), though the blood pressure was non-significantly lower. This was associated with improved survival (log-rank P<0.05) and neurological scores on day 3 (P<0.05). The Bax/Bcl-2 ratio of the brain 2 h post-CPR was lower in the MgSO4 group. The phosphorylated Akt and eNOS were also increased, suggesting activation of anti-apoptotic signaling via this pathway. Cotreatment with L-NAME (200 μM) abrogated not only the above changes but the enhanced cerebral perfusion. The survival and neurological benefits were also reversed.
Conclusion: MgSO4 employed during CPR and early post-resuscitation phase improves cerebral perfusion and overall prognosis. This is in part mediated by activation of Akt-eNOS signaling leading to anti-apoptotic protection. Since MgSO4 is readily available in daily practice, further translation to clinical study is viable for improving the post-resuscitation care and prognosis of the patients.