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The risk of overt and subtle cerebral injury may be higher in intracardiac operation (ICO) rather than coronary artery bypass grafting (CABG). S-100 protein is a specific astroglial protein whose serum level increases after cerebral injury. Elevated serum levels of S-100 have been detected after adult cardiac operations and correlated with neurologic injury.The level of S-100 protein was measured serially over 24 hours in 40 patients (27 undergoing aortic valve replacement, 9 mitral valve replacement, 4 closure of atrial septal defect) undergoing ICO and 20 patients undergoing CABG.The groups were similar with respect to age and cardiopulmonary bypass times. The S-100 level was not elevated before operation in any patient. Peak S-100 levels were reached at skin closure, when 35 of the ICO patients (88%) and 13 of the CABG patients (65%) had elevated S-100 levels. At skin closure peak S-100 levels were significantly greater in the ICO group (median [interquartile range], 0.76 [0.44-1.16] versus 0.3 [0-0.55] microgram/L; p0.01). At 5 hours S-100 levels were still elevated in 22 patients in the ICO group compared with 1 patient in the CABG group (p0.01), and at 24 hours 17 ICO patients had persistently elevated S-100 levels in comparison with 2 in the CABG group (p0.01). One valve patient had a stroke 24 hours after operation accompanied by a secondary increase in the S-100 level. There was no significant difference in postoperative S-100 levels between 5 patients in the ICO group with a prior history of stroke and those without. The peak S-100 level correlated with patient age (r = 0.59; p0.001) but not with the duration of cardiopulmonary bypass or core temperature during the operation.Intracardiac operation results in a significantly greater elevation in S-100 levels than CABG. Elevated S-100 levels correlate with increasing patient age but not with the duration of cardiopulmonary bypass or intraoperative core temperature. These findings raise the possibility that ICO patients may be more vulnerable to even subtle levels of cerebral injury than CABG patients.