Brain injury in canine models of cardiac surgery.
Neuropathology and neurologic impairment were characterized in a clinically relevant canine model of hypothermic (18°C) circulatory arrest (HCA) and cardiopulmonary bypass (CPB). Adult dogs underwent 2 hours of HCA (n = 39), 1 hour of HCA (n = 20), or standard CPB (n = 22) and survived 2, 8, 24, or 72 hours. Neurologic impairment and neuropathology were much more severe after 2-hour HCA than after 1-hour HCA or CPB; histopathology and neurologic deficit scores were significantly correlated. Apoptosis developed as early as 2 hours after injury and was most severe in the granule cells of the hippocampal dentate gyrus. Necrosis evolved more slowly and was most severe in amygdala and pyramidal neurons in the cornu ammonis hippocampus. Neuronal injury was minimal up to 24 hours after 1-hour HCA, but 1 dog that survived to 72 hours showed substantial necrosis in the hippocampus, suggesting that, with longer survival time, the injury was worse. Although neuronal injury was minimal after CPB, we observed rare apoptotic and necrotic neurons in hippocampi and caudate nuclei. These results have important implications for CPB in humans and may help explain the subtle cognitive changes experienced by patients after CPB.
From the Hugo W. Moser Research Institute at Kennedy Krieger (MEB, MAW, MSL, MVJ), Departments of Neurology (MEB, MAW, MVJ, JCT), Neuroscience (MEB, MAW), Pediatrics (MVJ), and Divisions of Neuropathology (JCT) and Cardiac Surgery (CAB, TJG, GJA, KAH, MJ, JB, WAB), The Johns Hopkins Medical Institutions, Baltimore, Maryland; and Perdana University Graduate School of Medicine, Kuala Lumpur, Malaysia (SM).
Mary E
ME
Blue
Mary Ann
MA
Wilson
Claude A
CA
Beaty
Timothy J
TJ
George
George J
GJ
Arnaoutakis
Kara A
KA
Haggerty
Melissa
M
Jones
Jeffrey
J
Brawn
Shaliza
S
Manmohan
Mary S
MS
Lange
Michael V
MV
Johnston
William A
WA
Baumgartner
Juan C
JC
Troncoso
D000818:Animals; D001930:Brain Injuries / Q000175:diagnosis* / Q000209:etiology*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D004195:Disease Models, Animal; D004285:Dogs; D008297:Male