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J Thorac Cardiovasc Surg 2005;129:1098-1103
© 2005 The American Association for Thoracic Surgery

Surgery for Congenital Heart Disease

Soluble {alpha}2-macroglobulin receptor is increased in endotracheal aspirates from infants and children after cardiopulmonary bypass

Eric A. Williams, MDa, Richard J. Ing, MB, BChb, Justin P. Hart, PhDc, James Jaggers, MDd, Frank H. Kern, MDa,b, Damian M. Craig, MSd, Salvatore V. Pizzo, MD, PhDc,*

a Departments of Pediatrics, Duke University Medical Center, Durham, NC
b Anesthesiology Duke University Medical Center, Durham, NC
c Pathology Duke University Medical Center, Durham, NC
d Surgery Duke University Medical Center, Durham, NC

Received for publication April 22, 2004; revisions received July 7, 2004; accepted for publication August 18, 2004.

* Address for reprints: Salvatore V. Pizzo, MD, PhD, Duke University Medical Center, Box 3712, Durham, NC 27710 (E-mail: willi055{at}mc.duke.edu).

OBJECTIVE: Cytokine dysregulation contributes to the systemic inflammatory response after cardiopulmonary bypass. Clearance of cytokine binding proteins may be important in the resolution of inflammation. Our aim was to determine whether the cytokine binding protein {alpha}2-macroglobulin and its soluble receptor were upregulated in endotracheal aspirates from infants and children undergoing cardiopulmonary bypass.

METHODS: Seventy tracheal aspirates were collected before and after cardiopulmonary bypass from 35 infants and children undergoing surgical correction of congenital heart defects. {alpha}2-Macroglobulin and the soluble {alpha}2-macroglobulin receptor were identified by Western blot. With the use of multi-analyte cytokine profiling, pro-inflammatory and anti-inflammatory cytokines were quantified, normalized to total protein, and expressed as ratios. Paired t tests and Wilcoxon signed-rank tests were performed between prebypass and postbypass samples. Correlations were examined among {alpha}2-macroglobulin, soluble {alpha}2-macroglobulin receptor, cytokine ratios, and the clinical variables of cardiopulmonary bypass, aortic crossclamp, and circulatory arrest times.

RESULTS: {alpha}2-Macroglobulin increased by 50% (mean densitometry increase 82,683 ± 184,594, P = .012), and soluble {alpha}2-macroglobulin receptor increased by 17% (mean densitometry increase 506,148 ± 687,037, P = .0001) after cardiopulmonary bypass. The ratio of interleukin-8/interleukin-4 increased by 136% (P = .0001), and interleukin-8/interleukin-10 increased by 102% (P = .001). The increase in soluble {alpha}2-macroglobulin receptor was positively correlated with the ratios of interleukin-8/interleukin-4 and interleukin-8/interleukin-10. There were no statistically significant positive correlations between the increase in {alpha}2-macroglobulin or soluble {alpha}2-macroglobulin receptor and measured clinical variables.

CONCLUSIONS: We report for the first time the upregulation of {alpha}2-macroglobulin and soluble {alpha}2-macroglobulin receptor in tracheal aspirates after cardiopulmonary bypass in infants and children. Soluble {alpha}2-macroglobulin receptor correlates with increased {alpha}2-macroglobulin and a disproportionate increase in pro-inflammatory to anti-inflammatory cytokine ratios.






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