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Apolipoprotein E Genotype and S100ß After Cardiac Surgery: Is Inflammation the Link?

Grocott, Hilary P. MD, FRCPC; Mackensen, G Burkhard MD

doi: 10.1213/01.ANE.0000156712.21918.BD
Letters to the Editor: Letters & Announcements

Department of Anesthesiology, Duke University Medical Center, Durham, NC, h.grocott@duke.edu

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To the Editor:

The recent report by Kofke et al. (1) outlining a relationship between apolipoprotein E genotype and serum markers of “cerebral injury” after cardiac surgery raises some interesting issues. At first glance, the hypothesis that biochemical markers of brain injury after cardiac surgery demonstrate larger increases in patients possessing the Apoε4 allele, an allele previously associated with worse neurologic outcome after cardiac surgery, (2) seems logical. However, their explanation that this relationship relates to the increased susceptibility of Apoε4 patients to cerebral ischemia during major vascular and cardiac surgery has some inherent flaws. The weakness in this argument stems from the fact that extracerebral sources for S100β have been identified; mediastinal blood aspirated by cardiotomy suction has been shown to have high concentrations of S100β (3). As a result, the use of the cardiotomy grossly contaminates the blood with S100β, making serum levels an unreliable surrogate of cerebral injury. Furthermore, the recent work by Fazio et al. has largely explained the true reason for the apparent extracerebral source for S100β (4). The commercially available assays used by Kofke et al. and others lack sufficient specificity for S100β, with the S100β signal representing other high molecular proteins (such as heptaglobin precursor I).

However, this does leave the question as to how the authors found this apparent relationship. A potential, although admittedly not exclusive, explanation for this may lie in an enhanced inflammatory response to cardiopulmonary bypass previously demonstrated in Apoε4-positive patients (5). An augmented inflammatory response may lead to increased bleeding (6) and if the Apoε4 patients bled more, they likely would have had more mediastinal and pericardial blood (with high S100β levels) returning to the venous reservoir via the cardiotomy suction and, as a result, have higher blood levels of S100β (7). Therefore, the link between S100β and Apoε4 is most likely unrelated to cerebral injury per se but may represent an indirect link to an enhanced inflammatory response.

Hilary P. Grocott, MD, FRCPC

G. Burkhard Mackensen, MD

Department of Anesthesiology

Duke University Medical Center

Durham, NC

h.grocott@duke.edu

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References

1. Kofke WA, Konitzer P, Meng QC, et al. The effect of apolipoprotein E genotype on neuron-specific enolase and S-100β levels after cardiac surgery. Anesth Analg 2004;99:1323–5.
2. Tardiff B, Newman M, Saunders A, et al. Preliminary report of a genetic basis for cognitive decline after cardiac operations. Ann Thorac Surg 1997;64:715–20.
3. Anderson RE, Hansson LO, Liska J, et al. The effect of cardiotomy suction on the brain injury marker S100β after cardiopulmonary bypass. Ann Thorac Surg 2000;69:847–50.
4. Fazio V, Bhudia SK, Marchi N, et al. Peripheral detection of S100β during cardiothoracic surgery: What are we really measuring? Ann Thorac Surg 2004;78:46–52.
5. Grocott HP, Newman MF, El-Moalem H, et al. Apolipoprotein E genotype differentially influences the proinflammatory and anti-inflammatory response to cardiopulmonary bypass. J Thorac Cardiovasc Surg 2001;122:622–3.
6. Tassani P, Augustin N, Barankay A, et al. High-dose aprotinin modulates the balance between proinflammatory and anti-inflammatory responses during coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2000;14:682–6.
7. Grocott HP, Arrowsmith JE. Serum S100 protein as a marker of cerebral damage during cardiac surgery. Br J Anaesth 2001;86:289–90.
© 2005 International Anesthesia Research Society