Hypoxic-ischemic brain injury in infants with congenital heart disease dying after cardiac surgery
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Cardiac surgery for congenital heart disease is performed increasingly earlier in infancy, including in the neonatal period. With increased survival of infants, there is growing concern about the long-term neurological sequelae of hypoxic-ischemic injury due to congenital heart disease itself prior to surgery, corrective surgery with the use of low-flow cardiopulmonary bypass (CPB) and/or deep hypothermic circulatory arrest (DHCA), and/or unstable hemodynamic factors postoperatively. In analyzing the neuropathology of 38 infants dying after cardiac surgery, we tested a set of questions related to the severity and patterns of brain injury, CPB, DHCA, and age of the infants at the time of surgery. In all infants dying after cardiac surgery, irrespective of the modality, cerebral white matter damage [periventricular leukomalacia (PVL) or diffuse white matter gliosis] was the most significant lesion in terms of severity and incidence, followed by a spectrum of gray matter lesions. There was no significant association between the duration of deep hypothermic circulatory arrest and the degree of severity of overall brain injury, and the pattern of brain injury was similar irrespective of the modality of cardiac surgery. There was no significant association between the age at the time of surgery (neonatal versus postneonatal) and the severity of overall brain injury. The patterns of brain injury were not age-related in the limited time-frame analyzed, except that infants who developed acute PVL after both closed and DHCA/CPB surgery (14/38 infants, 34%) were significantly younger at death (median age 13.0 days) compared to unaffected infants (median age at death 42.5 days) (P=0.031). This observation suggests that neonatal (<30 postnatal days), but not postneonatal (>30 postnatal days), brains are at risk for acute PVL, and likely reflects the vulnerability of immature (pre-myelinating) white matter to hypoxia-ischemia.
KeywordsDeep hypothermic circulatory arrest Infantile posterior column degeneration Inferior olivary gliosis Neonatal stroke Periventricular leukomalacia
Dr. Ashok Panigrahy was a Howard Hughes medical student research fellow at the time of this study. We acknowledge the input of Dr. Eva Chillenden in the initial phases of the work. We appreciate the helpful comments of Dr. Joseph J. Volpe, and the assistance of Mr. Richard A. Belliveau in manuscript preparation. This work was supported by NIH P30 HD-33703, and Children’s Hospital Mental Retardation Center Grant (P30-HD18655).
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