The proposed experiment utilizes weanling puppies to assess the cerebral effects of hypothermic circulatory arrest (HCA), a technique frequently required for correction of congenital heart disease in infancy. Despite more than twenty years of clinical use, there is still controversy over the safety of HCA, especially for durations > 60 minutes. The experimental animals will undergo surface and core cooling to an esophageal temperature of 13degreesC, and will be subjected to intervals of HCA ranging from 45 minutes to 2 hours: the control animals will undergo equivalent durations of low-flow cardiopulmonary bypass (CPB). Group I animals will undergo invasive procedures for serial measurements-- before and during cooling, immediately after HCA, and an late as 4 hours after reperfusion-- of cerebral oxygen consumption and glucose utilization; cerebrospinal fluid (CSF) content of lactate and enzymes whose presence is associated with cerebral ischemia; and cerebral blood flow (CBP). All the animals will have monitoring of quantitative electroencephalograms (EEG) during and immediately following the experiment. Group I animals will be sacrificed immediately following the HCA protocol. Group II animals will be followed for 2 weeks after undergoing the same HCA and CPB protocols in order to assess their neurological recovery. The long-term animals will have intraoperative determination of CBP and EEG so that they can be compared with the acute group, but will also have preoperative and serial postoperative EEGs, neurological examinations and behavioral assessments, an well as histopathological examination of their brains after sacrifice. From these experiments, it should be possible to define the safe limits of HCA, and to ascertain which acutely measured reflection of cerebral function is the best prognosticator of long-term neurological recovery. The results of the proposed study will greatly simplify future assessment of strategies to enhance cerebral protection during HCA, and may also prove useful clinically in identifying intraoperatively those patients at highest risk for neurological sequelae following HCA. These experimental results may also lead to better insight into the pathophysiology of cerebral damage during operations involving use of HCA.
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