The appearance of S-100 protein in serum during and immediately after cardiopulmonary bypass surgery: A possible marker for cerebral injury

doi:10.1016/S1053-0770(97)90160-9

Journal of Cardiothoracic and Vascular Anesthesia

Volume 11, Issue 6, October 1997, Pages 699-703

https://doi.org/10.1016/S1053-0770(97)90160-9 Get rights and content

Abstract

$Objective:$ To investigate the appearance and elimination of brain-specific S-100 protein in serum during and immediately after cardiopulmonary bypass.

$Design:$ Prospective study.

$Participants:$ Twenty-nine patients undergoing elective cardiac surgery.

$Interventions:$ Twenty-seven patients were operated on for coronary artery disease; two patients had valve replacement. Serial measurements of S-100 in arterial blood during and up to 48 hours after cardiopulmonary bypass were made.

$Measurements and Main Results:$ The perioperative and postoperative course was uneventful in 25 patients, with no clinical signs of neurologic complications. S-100 was not detected before extracorporeal circulation was started. Detectable concentrations (detection limit, 0.2 μg/L) appeared in serum after 10 minutes of perfusion and reached maximum levels, 2.43 ± 0.3 μg/L, at the end of bypass. The levels then declined with elimination t_$12$ of 2.2 hours. Only two patients had detectable concentrations of S-100 48 hours after the end of bypass. In four patients who developed clinical signs of cerebral injury, levels of S-100 were significantly higher at the end of bypass and 24 hours after the end of bypass.

$Conclusions:$ Cardiopulmonary bypass initiates a release of brain-specific S-100 to the systemic circulation. The release and elimination of S-100 seem to follow a reproducible pattern in patients with no signs of cerebral injury. In patients who developed cerebral injury, the concentrations of S-100 in blood were increased, thus suggesting that S-100 may be a usable marker for cerebral injury after extracorporeal circulation.

References (21)

ND Croughwell et al.
Jugular bulb saturation and cognitive dysfunction after cardiopulmonary bypass
Ann Thorac Surg
(1994)
R Donato
Perspectives in S-100 protein biology
Cell Calcium
(1991)
LJ Van Eldik et al.
S100β expression in Alzheimer's disease: Relation to neuropathology in brain regions
Biochim Biophys Acta
(1994)
A Usui et al.
Neural tissue-related proteins (NSE, G₀α, 28-kDa calbindin-D, S100b and CK-BB) in serum and cerebrospinal fluid after cardiac arrest
J Neurol Sci
(1994)
P Johnsson et al.
Cerebral complications after cardiac surgery assessed by S100 and NSE levels in blood
J Cardiothorac Vasc Anesth
(1995)
S Westaby et al.
S100 protein: A serum marker for cerebral injury during cardiopulmonary bypass
Ann Thorac Surg
(1996)
RF Rossi et al.
No flow or low flow?
K Brown et al.
Immunoreactive nervous system specific enolase (14-3-2-protein) in human serum and cerebrospinal fluid
Clin Chem Acta
(1980)
PJ Shaw et al.
Early intellectual dysfunction following coronary bypass surgery
Q J Med
(1986)
H Haimoto et al.
Differential distribution of immunoreactive S100-α and S100-β proteins in normal nonnervous human tissues
Lab Invest
(1987)

There are more references available in the full text version of this article.

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Citation Excerpt :
S100B (unlike other candidate biomarkers discussed) has also been detected in urine [42, 43]. Several studies have indicated that elevated serum S100B levels after cardiac operations with CPB are sensitive and specific for an ischemic stroke [44–46]. However, these studies found an immediate increase rather than the 2- to 3-day peak found in AIS studies, and none found a correlation between the increase and concurrent radiologic findings or neurologic deficit.
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^☆: Supported by grants from Malmö University Hospital and in part by Sangtec Medical AB, Bromma, Sweden.

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Original articleThe appearance of S-100 protein in serum during and immediately after cardiopulmonary bypass surgery: A possible marker for cerebral injury☆

Abstract

Ann Thorac Surg

Cell Calcium

Biochim Biophys Acta

J Neurol Sci

J Cardiothorac Vasc Anesth

Ann Thorac Surg

Clin Chem Acta

Early intellectual dysfunction following coronary bypass surgery

Q J Med

Differential distribution of immunoreactive S100-α and S100-β proteins in normal nonnervous human tissues

Lab Invest

Original article
The appearance of S-100 protein in serum during and immediately after cardiopulmonary bypass surgery: A possible marker for cerebral injury☆