TY - JOUR

T1 - Protein oxidation injury occurs during pediatric cardiopulmonary bypass

AU - Sheil, Meredith L

AU - Luxford, Catherine

AU - Davies, Michael Jonathan

AU - Peat, Jennifer K

AU - Nunn, Graham

AU - Celermajer, David S

PY - 2005/10

Y1 - 2005/10

N2 - 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.

AB - 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.

KW - Adolescent

KW - Cardiopulmonary Bypass

KW - Child

KW - Child, Preschool

KW - Dihydroxyphenylalanine

KW - Female

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Male

KW - Oxidation-Reduction

KW - Postoperative Complications

KW - Prospective Studies

KW - Tyrosine

U2 - 10.1016/j.jtcvs.2005.03.048

DO - 10.1016/j.jtcvs.2005.03.048

M3 - Journal article

C2 - 16214520

VL - 130

SP - 1054

EP - 1061

JO - Journal of Thoracic and Cardiovascular Surgery

JF - Journal of Thoracic and Cardiovascular Surgery

SN - 0022-5223

IS - 4

ER -