Apoptotic Activity is Increased in Brain Cortex Infarct after Hypothermic Circulatory Arrest in a Porcine Model

Abstract

Objective : It has been shown that apoptosis contributes to neuronal cell death after ischemia, and we evaluated the degree of apoptotic activity occurring in brain cortex of pigs after hypothermic circulatory arrest (HCA). Design : Thirty-one pigs underwent 75 min of HCA at 20°C. Histological examination of the brain was performed, and slides of brain cortex were evaluated for apoptotic activity by the TUNEL method. Results : Ten animals died during the first postoperative day and 21 survived until the seventh postoperative day. Brain cortex infarcts were found in animals that survived 7 days and these were included in this study. The median histopathological score among animals that died on the first postoperative day was 3.0 (range, 2-4), whereas it was 4.0 (range, 2-4) among survivors ( p = 0.019). The apoptotic index was particularly high in the area of the infarct, whereas only a few TUNEL-stained cells were observed in noninfarcted areas. The apoptotic index was nil in all pigs that died in the first postoperative period, whereas it was 2.0 (range, 0-6) among the animals that survived until the seventh postoperative day ( p < 0.0001). Conclusion : The apoptotic index was significantly increased in brain cortex infarcts of animals that survived 7 days after HCA, whereas only a few apoptotic cells were observed in noninfarcted areas of these animals as well as in animals that died on the first postoperative day. Further studies are required to elucidate the timing of development of brain infarction after HCA and whether neuroprotective strategies targeting the apoptotic process may mitigate brain damage.