Protein oxidation injury occurs during pediatric cardiopulmonary bypass.
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.
Sheil
Meredith L
ML
Adolph Basser Cardiac Institute, The Children's Hospital at Westmead, Sydney, Australia. Meredits@chw.edu.au
Luxford
Catherine
C
Davies
Michael J
MJ
Peat
Jennifer K
JK
Nunn
Graham
G
Celermajer
David S
DS
D000293:Adolescent; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004295:Dihydroxyphenylalanine / Q000097:blood*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010084:Oxidation-Reduction; D011183:Postoperative Complications / Q000097:blood / Q000453:epidemiology; D011446:Prospective Studies; D014443:Tyrosine / Q000097:blood*
D014443:Tyrosine; D004295:Dihydroxyphenylalanine