Ultrafast Cooling Induced by Total Liquid Ventilation Limits Early Oxidative Stress and Blood Brain Barrier Disruption After Cardiac Arrest

Introduction: We previously demonstrated that total liquid ventilation (TLV) with perfluorocarbons can afford ultra-fast cooling and improve outcome after non-shockable cardiac arrest in rabbits. Hypothesis: We determined whether this protection could be linked to an early inhibition of reperfusion injury after cardiac arrest, including oxidative stress and blood brain barrier (BBB) disruption. Methods: Anesthetized rabbits were randomly submitted to 13 min of asphyxia followed by cardiopulmonary resuscitation. Then, they randomly underwent normothermic life support (Control group) or hypothermia induced by either i.v. cold saline (30 ml/kg; CONV group) or TLV (TLV group). In a first set of experiments, reactive oxygen species (ROS) were measured by electron paramagnetic resonance spectroscopy using CMH as spin probe on tissues sampled 30 min after cardiac arrest. In a second set of experiments, BBB integrity was assessed by the administration of Evans blue dye (EBD) 30 min after resuscitation. Brains were sampled 2 h later for morphological examination of EBD leakage. Results: In the TLV group, the target temperature of 32°C was reached within 5-15 min in the entire body. In comparison, 30 min after cardiac arrest, rectal temperature was only 36.1±0.4 °C and 38.2±0.2 °C in the CONV and Control group, respectively. ROS production was significantly decreased in the TLV group in the brain (cortex), heart and kidneys but not in the CONV group as compared to Control (n=8 in each group; Figure). This was accompanied by a significant decrease in EBD leakage extent in TLV as compared to Control and CONV (4.3±0.0%, 26.1±0.1% and 20.8±0.1% of brain volume, respectively; n=5 each). Conclusion: Ultra-fast cooling mitigates early events after cardiac arrest through limitation of ROS production and BBB disruption. This could explain the dramatic effect of ultra-fast cooling as compared to delayed hypothermia after resuscitation.