Abstract 201: Neuroprotective Effect of Hypothermic Total Liquid Ventilation in Newborn Piglets Subjected to Neonatal Cardiac Arrest

Abstract

Introduction: Hypothermic total liquid ventilation (TLV) has been shown to be highly protective in adult models of cardiac arrest. Hypothesis: TLV could also provide benefits through ultrafast cooling during neonatal cardiac arrest and subsequent hypoxic-ischemic encephalopathy in piglets. Methods: Newborn piglets were anesthetized and submitted to 30 min of hypoxia (FiO 2 =10%) followed by 7 min of asphyxia. After resucitation, animals underwent either normothermic follow-up (38°C; Control, n=6) or ultra-fast cooling by TLV (TLV, n=6). TLV was implemented during 30 min for cooling induction and hypothermia was further maintained during 3 h using external techniques before rewarming. A third group of piglets was submitted to a Sham procedure (n=4) with neither hypoxia nor ischemia. All groups underwent mechanical ventilation during 6-8 h before awakening. Survival and neurological dysfunction were assessed during 7 days. Animals were then euthanized and histological brain damages were assessed (fluorojade-C staining). Results: After hypoxia-ischemia, Control and TLV animals presented marked metabolic acidosis and lactate levels elevation as compared to Sham (e.g., pH=6.91±0.05, 6.93±0.02 vs 7.33±0.05 at t=30 min after ischemia in Control, TLV and Sham, respectively; p<0.05). Despite a trend toward reduced mortality, survival was not significantly different between TLV and Control groups at the end of the survival follow-up (survival = 0/6, 3/6 and 3/4 in Control, TLV and Sham groups). Nevertheless, neurological dysfunction was significantly reduced in TLV as compared to Control (median scores = 23% vs 87 at day 2, respectively; Sham value = 0%). Blood levels of the brain injury biomarker protein S100B were also reduced at the time of euthanasia in TLV vs Control. Fluoro-jade C staining showed a significantly lower number of degenerating neurons in TLV vs Control (e.g., medians = 17 vs 39 degenerating neurons per field in caudate nucleus, respectively; Sham value = 1). Conclusion: Hypothermic TLV improves neurological recovery in a swine model of neonatal cardiac arrest and hypoxic-ischemic encephalopathy when started early after resuscitation.