Elderly patients will increasingly undergo cardiac surgery as the general population of elderly patients with heart disease increases each year. Age is an incremental risk factor for surgical complications in patients who have coronary artery bypass graft (CABG) surgery. Elderly patients appear to be especially at increased risk of suffering cognitive and neuropsychologic dysfunction postoperatively. The mechanism by which this occurs is not known. We propose to test the hypothesis that age-related impairment in cerebral autoregulation causes postoperative cognitive and neuropsychologic dysfunction in cardiac surgical patients. Both types of cerebral autoregulation will be tested: pressure-flow autoregulation and metabolism-flow autoregulation. This is the first prospective study of the postoperative incidence of neuropsychologic dysfunction in the elderly; the incidence of neuropsychologic dysfunction will be determined by neurologic and psychometric testing in 300 CABG patients over three years. The duration of cognitive dysfunction will be determined by serial testing. The hypothesis will be tested using Xe(133) clearance CBF determinations at two different temperatures (i.e., cerebral metabolic conditions) and two different perfusion pressures (i.e., pressure-flow conditions) during cardiopulmonary bypass. Cerebrospinal fluid (CSF) creatine phosphate brain specific isoenzyme and adenylate kinase will be measured at 24 hours after surgery as biochemical markers of ischemic damage postulated to result from impaired autoregulation and inadequate CBF during cardiopulmonary bypass. A comprehensive neuropsychological test battery will be administered on the day prior to surgery and at discharge (7 - 10 days), 6 weeks and 6 months post-CABG. Cardiopulmonary bypass (CPB) is an ideal model for manipulation of cerebral metabolism perfusion pressure and cannot be duplicated in other human experimental settings. Further, CPB is an excellent model for the study of neuropsychologic dysfunction since a relatively high incidence of events can be reproduced. The new knowledge generated in this investigation could lead to implementation of different management principles that could significantly reduce the incidence of this major complication of cardiac surgery in the elderly. Significantly, this will be the first examination in man of the integrity of cerebral blood flow autoregulation of the elderly and will provide new and important information about the physiology of aging.
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