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J Thorac Cardiovasc Surg 2005;130:1054-1061
© 2005 The American Association for Thoracic Surgery

Surgery for Congenital Heart Disease

Protein oxidation injury occurs during pediatric cardiopulmonary bypass

^a Adolph Basser Cardiac Institute, The Children's Hospital at Westmead, Sydney, Australia
^b Discipline of Pediatrics and Child Health, University of Sydney, Australia
^c The Heart Research Institute, Sydney, Australia
^d Department of Medicine, University of Sydney, Australia.

Received for publication November 29, 2004; revisions received February 15, 2005; accepted for publication March 31, 2005.

^_* Address for reprints: Meredith L. Sheil, MBBS, FACS, Adolph Basser Cardiac Institute, The Children's Hospital at Westmead, Cnr Hawkesbury Rd and Hainsworth St, Locked Bag 4001, Westmead, NSW, Australia 2145. (Email: Meredits{at}chw.edu.au).

OBJECTIVE: Proteins are the major effectors of biological structure and function. Oxidation-induced changes to protein structure can critically impair protein function, with important pathologic consequences. This study was undertaken to examine whether oxidation-induced changes to protein structure occur during pediatric cardiopulmonary bypass and to examine the association with postoperative outcome.

METHODS: Elevation of the 3,4-dihydroxyphenylalanine content of a protein relative to its native tyrosine content indicates structural damage due to oxidation. Protein 3,4-dihydroxyphenylalanine/native tyrosine ratios were measured before surgery and up to 6 hours after institution of cardiopulmonary bypass in 24 children undergoing repair of congenital heart disease, who were prospectively selected to form a cyanotic and comparable acyanotic control group. Results were correlated with perioperative variables and postoperative outcomes.

RESULTS: Elevation of protein 3,4-dihydroxyphenylalanine/tyrosine ratios above baseline (0.48 mmol/mol [SD, 0.11 mmol/mol] vs 0.36 mmol/mol [SD, 0.13 mmol/mol]; P = .001) occurred within 30 minutes of initiating cardiopulmonary bypass in cyanotic but not in acyanotic children and correlated inversely with preoperative arterial oxygen saturation (R = –0.52; P = .03). Protein 3,4-dihydroxyphenylalanine/tyrosine ratios were also increased above baseline at 120 minutes (0.44 mmol/mol [SD, 0.12 mmol/mol]; P = .007) and 180 minutes (0.40 mmol/mol [SD, 0.14 mmol/mol]; P = .01) after the institution of cardiopulmonary bypass in children who underwent prolonged procedures. Elevation of 3,4-dihydroxyphenylalanine/tyrosine during prolonged procedures was associated with postoperative arrhythmias and the need for increased inotropic support (P = .001).

CONCLUSIONS: Oxidative injury to proteins occurs during pediatric cardiopulmonary bypass. Cyanotic children are most at risk, particularly those undergoing prolonged procedures, in whom elevation of the protein 3,4-dihydroxyphenylalanine/tyrosine ratio is associated with increased postoperative morbidity.