Regional patterns of neuronal death after deep hypothermic circulatory arrest in newborn pigs.
OBJECTIVE
Deep hypothermic circulatory arrest (DHCA) widely used during neonatal heart surgery, carries a risk of brain damage. In adult normothermic ischemia, brain cells in certain regions die, some by necrosis and others by apoptosis (programmed cell death). This study characterized regional brain cell death after DHCA in newborn pigs.


METHODS
Eighteen piglets underwent 90 minutes of DHCA and survived 6 hours, 2 days, or 1 week. Six piglets underwent surgery alone or deep hypothermic cardiopulmonary bypass and survived 2 days. Three piglets received no intervention (control). Brain injury was assessed by neurologic and histologic examination and correlated with perioperative factors. Apoptosis and necrosis were identified by light microscopic analysis of cell structure and in situ DNA fragmentation (TUNEL).


RESULTS
All groups subjected to DHCA had brain injury by neurologic and histologic examination, whereas the other groups did not. DHCA damaged neurons in the neocortex and hippocampus and occasionally in the striatum and cerebellum. Damaged neurons in the neocortex were mainly apoptotic and in the hippocampus, a mixture of necrotic and apoptotic neurons. Apoptosis and necrosis were apparent in all DHCA groups even though neurologic deficits improved over the week's survival. Neocortical and hippocampal damage correlated with blood glucose, hematocrit, and arterial PO(2) during and after cardiopulmonary bypass.


CONCLUSIONS
In neonates, neocortical and hippocampal neurons are selectively vulnerable to death after DHCA. Both apoptosis and necrosis contribute to neuronal death, beginning early in reperfusion and continuing for days. These data suggest the need for several neuroprotective strategies tailored to the region and death process, initiated during the operation and continued after the operation.
Kurth
C D
CD
Brain Research Laboratory, Joseph Stokes Research Institute, Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, PA 19104, USA. kurth@email.chop.edu
Priestley
M
M
Golden
J
J
McCann
J
J
Raghupathi
R
R
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001786:Blood Glucose / Q000032:analysis; D001921:Brain / Q000473:pathology*; D002315:Cardiopulmonary Bypass; D016923:Cell Death; D002531:Cerebellum / Q000473:pathology; D003342:Corpus Striatum / Q000473:pathology; D053938:DNA Fragmentation; D006324:Heart Arrest, Induced; D006400:Hematocrit; D006624:Hippocampus / Q000473:pathology; D007036:Hypothermia, Induced; D020287:In Situ Nick-End Labeling; D009336:Necrosis; D019579:Neocortex / Q000473:pathology; D009474:Neurons / Q000166:cytology*; D010100:Oxygen / Q000097:blood; D012044:Regression Analysis; D015424:Reperfusion; D012307:Risk Factors; D015996:Survival Rate; D013552:Swine
D001786:Blood Glucose; D010100:Oxygen