Correlation Between CSF and Serum S-100 Protein after Cerebral Ischemia in Pigs on Cardiopulmonary Bypass

Abstract

Introduction: One potential marker of central nervous system damage during cardiac surgery is the astroglial protein S-100, which has been shown to increase with the duration of cardiopulmonary bypass (CPB) [1]. However, recovery of the S-100 protein in blood has not been directly correlated with functional or histopathological outcomes after CPB. Part of the diagnostic problem may be related to whether concentration of this protein marker in the serum correlates with cerebrospinal fluid (CSF). In a porcine model of global cerebral ischemia during CPB, we examined the presence of S-100 in the sagittal sinus after bypass and correlated serum and CSF S-100 levels. Methods: In an approved study, sagittal sinus catheters were placed in 40 anesthetized pigs. Animals were cannulated and placed on CPB. Baseline serum S-100 levels from the sagittal sinus were obtained. Electroencephalographic (EEG) signals from scalp needle electrodes assessed the severity of cerebral ischemia. All animals underwent 15 minutes of global cerebral ischemia produced by temporarily ligating the innominate and left subclavian arteries followed by reperfusion. Thirty minutes after discontinuing CPB, a needle was inserted into the cisterna magna to collect CSF; simultaneously, a sample of sagittal sinus blood was aspirated. S-100 protein contents were analyzed using a monoclonal immunoradiometric assay (Sangtec Medical, Sweden). Results: Cerebral ischemia was confirmed by total loss of EEG activity. Sagittal sinus S-100 levels at baseline were 0.09 +/- 0.06 [micro sign]g/L and increased significantly after ischemia (0.24 +/- 0.22 [micro sign]g/L; p<0.05). After bypass, CSF S100 levels were significantly greater than corresponding serum concentrations: 4.35 +/- 3.1 [micro sign]g/L (p<0.05). There was a weak linear correlation (r=0.37) between serum and CSF S-100 concentrations after CPB (p<0.02; Figure 1).Figure 1Discussion: Serum S-100 protein in the sagittal sinus increased significantly after ischemia, confirming the usefulness this assay to detect cerebral ischemic injury during CPB. However, the variable relationship between blood and CSF sites may indicate short-lived, reversible changes in blood-brain barrier permeability after ischemia on CPB. The amount of ischemic cerebral damage as measured by CSF S-100 protein concentration may not be reflected by serum S-100 values.