Abstract 2046: Hypercapnic Resuscitation Improves Survival and Neurological Outcomes by Nitric Oxide Synthase-Mediated Enhancement of Brain Perfusion
Neurological injury is one of the major causes of morbidity and mortality following cardiac arrest and cardiopulmonary resuscitation (CPR). Brain perfusion is usually compromised in the post-resuscitation phase, which inevitably lengthens the ischemic insult of the brain. Hypercapnia has been reported to cause cerebral vasodilatation. We therefore sought to study the potentials of hypercapnic resuscitation in improving the brain perfusion as well as survival and neurological prognoses. Using an established rat model of asphyxial cardiac arrest (6 min) and CPR, we employed hypercapnic (5% CO2, 95% O2) ventilation during CPR and the first 2 h post-resuscitation, and compared the brain perfusion with normocapnia (5% N2, 95% O2) control. The blood pressure was continuously monitored, with arterial blood sampled regularly for gas analysis. The tissue perfusion of the brain was measured by OxyLyte 2000E perfusion sensor. In a subgroup the survival and neurological outcomes were monitored up to 3 days. TdT-mediated dUTP nick-ends labeling (TUNEL) stain and Bax/Bcl2 of the brain were assessed as indicators of apoptotic cell death. The PaCO2 was significantly higher (P<0.001) and pH significantly lower (P<0.001) in hypercapnia group during the first 2 h post-resuscitation. No difference was noted in PaO2 or blood pressure. In normocapnia control, the brain perfusion was significantly reduced in the first 30 min post-resuscitation. Hypercapnic ventilation enhanced brain perfusion during this period (P<0.05). The survival and neurological outcomes were also improved (LogRank P<0.05), which was consistent with the decrease in TUNEL stain and Bax/Bcl2. If nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) was cotreated with hypercapnia, the increased brain perfusion and reduced TUNEL and Bax/Bcl2 were reversed. The improved survival and neurological outcomes were also abrogated. Hypercapnic ventilation during CPR and early post-resuscitation phase improves brain perfusion and hence survival and neurological outcomes. This is in part mediated by NO synthase-related vasodilatation.