Hippocampal neuronal death following deep hypothermic circulatory arrest in dogs: involvement of apoptosis.
This study was undertaken to evaluate the histological nature of brain damage caused by deep hypothermic circulatory arrest during cardiopulmonary bypass. Total body cooling to 15 degrees C and rewarming were performed with a conventional cardiopulmonary bypass technique using the femoral artery and vein. Dogs were assigned to one of three groups. In group 1 (n = 4), cardiopulmonary bypass was maintained in a state of deep hypothermia (15 degrees C) for 90 min, group 2 animals (n = 5) underwent 60 min of deep hypothermic circulatory arrest at 15 degrees C, and group 3 (n = 6) underwent 90 min of deep hypothermic circulatory arrest at 15 degrees C. All dogs were killed by perfusion fixation 72 h after cardiopulmonary bypass. The CA1 regions of the hippocampi were examined by light and electron microscopy. Biotinylated dUTP was used for nick-end labeling of apoptotic cells mediated by terminal deoxytransferase. No morphological change was observed in group 1 dogs, and very little in group 2 dogs. More severe neuronal damage was observed in group 3. The nuclei of many cells were shrunken and showed nick-end labeling. Dense chromatin masses were detected electron microscopically in the nuclei of CA1 pyramidal cells. Neuronal cell death observed in CA1 pyramidal cells 72 h after 90 min of deep hypothermic circulatory arrest at 15 degrees C involves apoptosis. Therefore, according to this model, the maximum duration of deep hypothermic circulatory arrest should not be allowed to exceed 60 min.
Kin
H
H
Third Department of Surgery, Iwate Medical University School of Medicine, Morioka, Japan.
Ishibashi
K
K
Nitatori
T
T
Kawazoe
K
K
D000818:Animals; D017209:Apoptosis; D001925:Brain Damage, Chronic / Q000503:physiopathology*; D004285:Dogs; D005069:Evaluation Studies as Topic; D006324:Heart Arrest, Induced; D006624:Hippocampus / Q000473:pathology*; D007036:Hypothermia, Induced; D009474:Neurons / Q000473:pathology; D017966:Pyramidal Cells / Q000473:pathology; D011897:Random Allocation; D013997:Time Factors