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

Kofke, W Andrew MD, MBA; Cheung, Albert MD; Konitzer, Patrick MD

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

Departments of Anesthesia and Neurosurgery, University of Pennsylvania, Philadelphia, PA, andrew.kofke@uphs.upenn.edu

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In Response:

Dr. Grocott’s insights that factors other than neurologic injury could provide alternative explanations for the observed increase in S100β levels in patients with the ApoE4 genotype undergoing cardiac operations are helpful and appreciated. This certainly underscores the need for ongoing research to find a reliable plasma biomarker for brain injury (1) and raises important issues about our interpretations. Despite the limitations of using S100β, with the older assay, as a biomarker for brain injury, the potential neurologic implications of the study cannot be completely discounted.

We reported an observation of a postcardiac surgery association between S100β and the ApoE4 genotype. The possible causes for this, as we suggested, include (but do not prove) neurologic injury. Nonetheless, the possibility of a neurologic contribution to our findings cannot be totally discounted, as this notion is supported by: a) previous observations of worse cognitive outcome after cardiac surgery in ApoE4 positive patients (2), b) observations that postoperative levels of S100β correlate with cognitive outcome after cardiac surgery (3), c) correlating increases in neuron-specific enolase and S100β reported in our study and in previous work (4), and d) increases in neuron-specific enolase and S100β from effluent blood of retrograde-perfused brains of patients undergoing deep hypothermic arrest (4).

Dr. Grocott’s alternative hypothesis that the increased S100β and neuron-specific enolase may have been caused by inflammatory responses to surgery and extracorporeal circulation and that patients with the ApoE4 genotype may exhibit exaggerated inflammatory responses is reasonable and novel. This explanation may also be interpreted as consistent with our conclusion because neurologic injury is often associated with, or pathophysiologically related to, inflammatory processes. Thus, as Dr. Grocott correctly suggests, all of these biomarker correlations really may be nothing more than epiphenomena for more fundamental processes like inflammation or increased bleeding. We hope future work will provide the answer.

W. Andrew Kofke, MD, MBA

Albert Cheung, MD

Patrick Konitzer, MD

Departments of Anesthesia and Neurosurgery

University of Pennsylvania

Philadelphia, PA

andrew.kofke@uphs.upenn.edu

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References

1. Siman R, McIntosh TK, Soltesz KM, et al. Surrogate markers for experimental brain damage in the rat. Program No. 11.3. 2003 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2003. Available at: http://sfn.scholarone.com/itin2003/index.html. Accessed December 1, 2004.
2. Tardiff BE, Newman MF, Saunders AM, et al. Preliminary report of a genetic basis for cognitive decline after cardiac operations. Ann Thorac Surg 1997;64:715–20.
3. Georgiadis D, Berger A, Kowatschev E, et al. Predictive value of S-100beta and Neuron specific enolase serum levels for adverse neurologic outcome after surgery. J Thorac Cardiovasc Surg 2000;119:138–47.
4. Cheung AT, Stecker MM, Weiss SJ, et al. Astrocyte S-100 (S-100) and neuron-specific enolase (NSE) increase during circulatory arrest with retrograde cerebral perfusion (RCP). Anesthesiology 1999;91:A77.
© 2005 International Anesthesia Research Society