Experimental evaluation of a model of neonatal hypoxic-ischemic encephalopathy in newborn piglets

Introduction Hypoxic-ischemic encephalopathy is a frequent and unexpected birth complication causing major neurological disorders in newborn infants. Objectives Our goal was to elaborate a standardized protocol of hypoxia-ischemia in piglets for the further evaluation of innovating cardio- and neuroprotective strategies. Method Newborn piglets were anesthetized and submitted to 30 min of hypoxia (FiO 2  = 10%) followed by ischemia induced by 7 minutes of respiratory arrest (HI group). Cardiopulmonary resuscitation was instituted through external cardiac massage and epinephrine administration (4 μg/kg, i.v.). Another group of piglets was submitted to a Sham procedure with neither hypoxia nor ischemia. In both groups, animals were maintained under mechanical ventilation during 6 hours. After weaning, survival and neurological dysfunction were assessed during 7 days. Animals were then euthanized and histologic damage was assessed in the brain (HE and fluorojade-B staining). Results Eight and four animals were submitted to HI or Sham procedure, respectively. In the HI group, a severe bradycardia and hypotension was observed at the end of the ischemic period (mean arterial pressure = 28 ± 2 vs. 59 ± 3 mmHg in HI vs. Sham, respectively; P t  = 30 min post-ischemia in HI vs. Sham, respectively; P Conclusion This model is suitable for the evaluation of new protective therapies after neonatal asphyxia.