Hypothermia at 10 degrees C reduces neurologic injury after hypothermic circulatory arrest in the pig.
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.
Ananiadou
Olga G
OG
Department of Cardiac Surgery, University Hospital of Ioannina, Ioannina, Greece.
Bibou
Katerina
K
Drossos
George E
GE
Bai
Mary
M
Haj-Yahia
Saleem
S
Charchardi
Antonia
A
Johnson
Elizabeth O
EO
D000818:Animals; D017209:Apoptosis; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002315:Cardiopulmonary Bypass; D050792:Circulatory Arrest, Deep Hypothermia Induced / Q000009:adverse effects*; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D007036:Hypothermia, Induced; D019344:Lactic Acid / Q000097:blood; D008297:Male; D016343:Monitoring, Intraoperative; D012107:Research Design / Q000706:statistics & numerical data; D013194:Staining and Labeling / Q000379:methods; D013552:Swine; D016896:Treatment Outcome
D019344:Lactic Acid