RESUMO
BACKGROUND: We have previously reported that sensory, motor neocortex, and hippocampus are selectively vulnerable to injury in an acute porcine model of HCA at 18 degrees C. This study was undertaken to assess whether further cooling to 10 degrees C can reduce neurological injury during HCA. METHODS: Twelve piglets underwent 75 minutes of HCA at 18 degrees C (n = 6) and 10 degrees C (n = 6). Four served as normal controls. After gradual rewarming and 80 minutes of reperfusion, treatment animals were sacrificed and brains were perfusion-fixed and cryopreserved. Regional patterns of neuronal apoptosis after HCA were characterized by in situ DNA fragmentation using TUNEL histochemistry. Hematoxylin and eosin histology was used to characterize cell damage morphologically. TUNEL-positive cells were scored on a scale of 0 to 5. Grade 0: no TUNEL-positive cells; Grade 1: < 10%; Grade 2: 10% to 25%, Grade 3: 25% to 50%, Grade 4: 50% to 75%; and Grade 5: > 75%. RESULTS: TUNEL-positive cells indicating DNA fragmentation were scored in the motor and sensory neocortex, hippocampus, cerebellum, thalamus, and medulla of animals treated with 18 degrees C and 10 degrees C HCA and were significantly greater than in normal controls. Profound cooling to 10 degrees C resulted in a significant reduction of neuronal injury in the neocortex and hippocampus. CONCLUSIONS: This data support that cerebral protection may be better at very cold temperatures compared to 18 degrees C hypothermia. Regions selectively vulnerable to neuronal injury are offered more neural protection by profound hypothermia. These affects are observed in the acute state, suggesting activation of the apoptotic mechanisms at early stages can be inhibited by profound hypothermia.
Assuntos
Lesões Encefálicas/prevenção & controle , Parada Circulatória Induzida por Hipotermia Profunda/efeitos adversos , Hipotermia Induzida , Animais , Apoptose , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Ponte Cardiopulmonar , Fragmentação do DNA , Modelos Animais de Doenças , Ácido Láctico/sangue , Masculino , Monitorização Intraoperatória , Projetos de Pesquisa/estatística & dados numéricos , Coloração e Rotulagem/métodos , Suínos , Resultado do TratamentoRESUMO
OBJECTIVES: Although deep hypothermic circulatory arrest (HCA) is routinely used to interrupt normal perfusion of the brain and prevent subsequent cerebral ischemic injury during cardiac surgery, it is associated with various forms of neurologic disturbances. Neurologic sequelae after prolonged HCA include motor, memory and cognitive deficits. The present study was designed to assess acute regional neuronal injury after HCA in an animal model. METHODS: Six piglets underwent 75 min of HCA at 18 degrees C. Four piglets served as normal controls. After gradual rewarming and reperfusion, treatment animals were killed and their brains were perfusion-fixed and cryopreserved. Regional patterns of neuronal apoptosis after HCA was characterized by in situ DNA fragmentation using terminal deoxyneucleotidyl-transferase-mediated biotin-dUTP nick end-labeling (TUNEL) histochemistry. Hematoxylin and eosin histology was used to characterize cell damage morphologically. TUNEL-positive cells were scored on a scale of 0 to 5. Grade 0: no TUNEL-positive cells; Grade 1: <10%, Grade 2: 10-25%, Grade 3: 25-50%, Grade 4: 50-75%; and Grade 5: >75%. RESULTS: TUNEL-positive cells indicating DNA-fragmentation were scored in the precentral gyrus (motor neocortex), postcentral gyrus (sensory neocortex), hippocampus, cerebellum, thalamus and ventral medulla of HCA treated animals and were significantly greater than in normal controls (P