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J Thorac Cardiovasc Surg 1999;117:843-844
© 1999 Mosby, Inc.

LETTERS TO THE EDITOR

Serum S-100 protein levels after pediatric cardiac surgery: A possible new marker for postperfusion cerebral injury

Hashim Abdul-Khaliq, MDa, Vlademir Alexi-Meskhishvili, MD, PhD b, Peter E. Lange, MD, PhDa

Clinical Professor EmeritusDepartment of Congenital Heart Disease and Pediatric Cardiologya
Department of Thoracic and Cardiovascular Surgeryb
Deutsches Herzzentrum Berlin
Berlin, Germany

Serum S-100 protein levels after pediatric cardiac surgery: A possible new marker for postperfusion cerebral injury

To the Editors:

We read with great interest the publication of Lindberg and associatesGo 1 in this Journal on the serum S-100 protein levels after pediatric cardiac surgery.

In our institution we have used this marker as a routine biochemical monitoring parameter before and after corrective cardiac operations in infants. We have published several studies concerning the release patterns of S-100 in association with other neurologic monitoring methods, such as near-infrared spectroscopy and transcranial Doppler sonography.

We have also found a close relationship between the age and weight at operation and the measured peak values before and after cardiopulmonary bypass (CPB).Go 2 Our postoperative release patterns in infants and children are similar to those results of Lindberg and colleagues. The postoperative peak values correlated to age (r = –0.77, P < .0001) and weight (r = –0.71, P < .0001) of the studied infants.Go 2

In the study of Lindberg and associates, however, we miss the presence of a control group to show that the protein S-100 levels are not similarly increased after operations without CPB. As appropriate controls, we use infants undergoing corrective surgery for coarctation of the aorta without CPB.

It remains unclear whether these transient elevations of postbypass S-100 values indicate "normal patterns," inasmuch as infants with evident clinical brain injury had much higher levels, more than 2 SD of those without cerebral and neurologic complications (Fig 1). Possible subclinical brain injury associated with transient elevation of the serum levels of protein S-100, therefore, have to be evaluated with the use of additional neurophysiologic methods and neurodevelopmental follow-up studies. Higher serum concentrations than the peak S-100 values in all infants were found in 5 infants with neurologic and cardiac complications (Fig 1Go).



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  		Fig 1. Release patterns of S-100 protein in infants and children with and without neurologic abnormalities. CT, Computed tomography; TOF, tetralogy of Fallot; IVH, intraventricular hemorrhage; d-TGA, dextro-transposition of the great arteries; CAVC, complete atrioventricular canal; CPB, cardiopulmonary bypass; SD, standard deviation.

 
Seizure activity during the early postoperative period has been suggested to have powerful neurologic predictive value in follow-up of infants after corrective surgery in early life.Go 4 This is in agreement with our findings and with the observation of Lindberg in one case in his study, in which a marked increase of the protein S-100 serum levels was found immediately after the onset of seizure activity.Go 1

We also agree with Lindberg and his coauthors' speculation that the possible lack of maturation of the blood-brain barrier may be a factor causing the higher release of protein S-100 in neonates than in infants.Go 2 However, in addition to the inflammatory processes, oxygen-derived free radicals induce endothelial reperfusion injury and may contribute to the alteration of the blood-brain barrier.Go 5 Thus measurement of malondialdehyde, a fragment of lipid peroxidation, in the serum may provide possible information on accentuated structural membrane injuryGo 5 by free radicals.Go Go 5,6

Significant increases of malondialdehyde values, as well as a concomitant significant increase of the serum concentration of the astroglial protein S-100, were found between crossclamping and unclamping of the aorta.Go 6

In conclusion, we found similar age-dependent release patterns of the protein S-100 in neonates and infants in comparison with infants undergoing surgery without CPB. A pathologic mechanism underlying the release of protein S-100 in the serum might be an induced reperfusion injury and possible transient functional and/or structural alteration of the brain-blood barrier.

12/8/95918

References

  1. Lindberg L, Olsson A-K, Anderson K, Jögi P. Serum S-100 protein levels after pediatric cardiac operation: a possible new marker for postperfusion cerebral injury. J Thorac Cardiovasc Surg 1998;116:281-5. [Abstract/Free Full Text]
  2. Abdul-Khaliq H, Uhlig R, Rützler K, Dähnert I, Alexi-Meskhishvili V, Ewaldt E, Hetzer R, et al. The protein S-100: a marker of cerebral injury associated with cardiac surgery in infants? In: Imai Y, Momma K, editors. Proceedings of Second World Congress of Pediatric Cardiology and Cardiac Surgery. Armonk [NY]. Futura; 1998. p. 902-4.
  3. Rützler K, Abdul-Khaliq H, Uhlig R, Dähnert I, Alexi-Meskhishvili V, Abraham K, Hetzer R, et al. Altersabhängigkeit des nachweisbaren Serumproteins S-100 während und nach Korrekturoperation angeborener Herzfehler im Kleinkindesalter. Z Herz Thorax Gefäflchir 1998;12:2-7.
  4. Rappaport LA, Wypij D, Bellringer DC, Helmers SL, Holmes GL, Barnes PD, et al. Relation of seizures after cardiac surgery in early infancy to neurodevelopmental outcome. Circulation 1998;97:773-9. [Abstract/Free Full Text]
  5. Kunstmann S, Mertsch K, Blasig IE, Grune T. High metabolic rates of 4-hydroxynonenal in brain capillary endothelial cells during hypoxia/reoxygenation. Brain Res 1996;740:353-5.[Medline]
  6. Abdul-Khaliq H, Blasig IE, Baur MO, Hohlfeld M, Alexi-Meskhishvili V, Lange PE. Release of the cerebral protein S-100 into blood after reperfusion during cardiac surgery in infants: Is there a relation to oxygen radical–induced lipid peroxidation? J Thorac Cardiovasc Surg. In press.




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