title: Injury pattern of the neonatal brain after hypothermic low-flow cardiopulmonary bypass in a piglet model.
abstract: Low-flow cardiopulmonary bypass (LF-CPB) is a widely used modality in neonatal heart surgery. While facilitating surgical repair, it poses a risk of neurological injury caused by hypoperfusion. In the present study, we characterize the injury pattern and influencing factors in a piglet hypothermic LF-CPB model. Piglets were anesthetized, tracheally intubated, ventilated, and prepared for CPB. After LF-CPB for 150 min at 22 degrees C (brain) using pH-stat strategy, animals were allowed to survive for 2 or 9 days. Neurological status was assessed daily and magnetic resonance imaging scans were performed. Brains were assessed histologically. Functional neurological impairment was seen in 64%, 30%, and 0% of animals 1, 2, and 9 days after CPB, respectively. All animals showed histological brain damage, predominantly in neocortex and hippocampus, less so in basal ganglia, thalamus, white matter, and cerebellum. Cell death appeared as selective neuronal necrosis in the deeper layers in neocortex and CA1-4 sections in hippocampus. Even in a pH-stat strategy, less neocortical and hippocampal damage correlated with higher arterial partial pressure for carbon dioxide. Less hippocampal damage was associated with higher blood glucose levels. Less functional neurological impairment and basal ganglia damage correlated with higher postoperative hematocrit.
  
  
  CONCLUSIONS
  Neuronal injury after hypothermic low-flow cardiopulmonary bypass in a piglet model using pH-stat strategy occurs predominantly in deep neocortex and hippocampus. Factors mitigating injury were higher arterial carbon dioxide, hematocrit, and blood glucose levels.
authors.affiliation: *Department of Anesthesia, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, and Institute of Pediatric Anesthesia, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio; and †Department of Pathology, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Loepke
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Golden
authors.forename: John C
authors.initials: JC
authors.lastname: McCann
authors.forename: C Dean
authors.initials: CD
authors.lastname: Kurth
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001794:Blood Pressure; D001831:Body Temperature; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000473:pathology*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002560:Cerebrovascular Circulation / Q000502:physiology; D006339:Heart Rate; D007036:Hypothermia, Induced; D008279:Magnetic Resonance Imaging; D009460:Neurologic Examination; D017694:Rewarming; D013534:Survival; D013552:Swine