Children undergoing surgical repair of congenital cardiac anomalies are at significant risk of brain injury. In contrast to adults in whom the cause of brain injury during cardiac surgery is most commonly fixed or embolic atherosclerosis, in children the cause is most commonly global hypoxia/ischemia. The first hypothesis to be tested in the proposed study is that global cerebral hypoxia/ischemia results from definable, additive interactions of the extreme manipulations of perfusion parameters that are employed in pediatric cardiac surgery, namely extreme degrees of low perfusion flow, hypothermia, hemodilution and pH shifts, which can result in impaired oxygen delivery to cerebral mitochondria. Near infrared spectroscopy is a mew method of real-time brain monitoring that offers the potential to detect impending critical cerebral hypoxia/ischemia. This technique offers distinct advantages over current indirect methods of monitoring brain function because of its capacity to define successful delivery of oxygen to neuronal mitochondria through assessment of the redox state of cytochrome aa3. This study will define a critical threshold of cytochrome aa3 reduction using standard continuous wave near infrared spectroscopy. This threshold for cerebral injury will be validated using a novel invasive method of near infrared spectroscopy that measures absolute changes in both hemoglobin and mitochondrial oxygenation. After the first phase of the study has defined the critical threshold of injury, the second phase of the study will test the second hypothesis that real time monitoring with near infrared spectroscopy can allow manipulation of perfusion parameters such that neurological injury is avoided. The study will shed light on the mechanisms by which flow rate, temperature, hematocrit and pH interact to determine intraneuronal oxygen delivery. It also will demonstrate the utility of near infrared spectroscopy as a clinical method for avoid brain injury during pediatric cardiac surgery.
| Lu, Zhaohui; Korotcova, Ludmila; Murata, Akira et al. (2014) Aprotinin, but not ?-aminocaproic acid and tranexamic acid, exerts neuroprotection against excitotoxic injury in an in vitro neuronal cell culture model. J Thorac Cardiovasc Surg 147:1939-45 |
| Murata, Akira; Agematsu, Kota; Korotcova, Ludmila et al. (2013) Rodent brain slice model for the study of white matter injury. J Thorac Cardiovasc Surg 146:1526-1533.e1 |
| Ishibashi, Nobuyuki; Scafidi, Joseph; Murata, Akira et al. (2012) White matter protection in congenital heart surgery. Circulation 125:859-71 |
| Okamura, Toru; Ishibashi, Nobuyuki; Kumar, T Susheel et al. (2010) Hypothermic circulatory arrest increases permeability of the blood brain barrier in watershed areas. Ann Thorac Surg 90:2001-8 |
| Singh, R K; Stephens, S; Berl, M M et al. (2010) Prospective study of new-onset seizures presenting as status epilepticus in childhood. Neurology 74:636-42 |
| Ishibashi, Nobuyuki; Iwata, Yusuke; Okamura, Toru et al. (2010) Differential neuronal vulnerability varies according to specific cardiopulmonary bypass insult in a porcine survival model. J Thorac Cardiovasc Surg 140:1408-15.e1-3 |
| Okamura, Toru; Ishibashi, Nobuyuki; Zurakowski, David et al. (2010) Cardiopulmonary bypass increases permeability of the blood-cerebrospinal fluid barrier. Ann Thorac Surg 89:187-94 |
| Iwata, Yusuke; Nicole, Olivier; Okamura, Toru et al. (2010) Aprotinin confers neuroprotection by reducing apoptotic cell death. Asian Cardiovasc Thorac Ann 18:170-3 |
| Iwata, Yusuke; Nicole, Olivier; Zurakowski, David et al. (2010) Ibuprofen for neuroprotection after cerebral ischemia. J Thorac Cardiovasc Surg 139:489-93 |
| Iwata, Yusuke; Okamura, Toru; Ishibashi, Nobuyuki et al. (2009) Optimal dose of aprotinin for neuroprotection and renal function in a piglet survival model. J Thorac Cardiovasc Surg 137:1521-9; discussion 1529 |
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