Hippocampal neuronal death following deep hypothermic circulatory arrest in dogs: involvement of apoptosis

This study was undertaken to evaluate the histological nature of brain dama ge caused by deep hypothermic circulatory arrest during cardiopulmonary byp ass. 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), cardi opulmonary 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 hypothermi c 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 kille d by perfusion fixation 72 h after cardiopulmonary bypass. The CA1 regions of the hippocampi were examined by light and electron microscopy. Biotinyla ted dUTP was used for nick-end labeling of apoptotic cells mediated by term inal 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 lab eling. Dense chromatin masses were detected electron microscopically in the nuclei of CA1 pyramidal cells. Neuronal cell death observed in CA1 pyramid al cells 72 h after 90 min of deep hypothermic circulatory arrest at 15 deg rees C involves apoptosis. Therefore, according to this model, the maximum duration of deep hypothermic circulatory arrest should not be allowed to ex ceed 60 min. (C) 1999 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved.