蛋白质氧化损伤发生在小儿体外循环期间。

Protein oxidation injury occurs during pediatric cardiopulmonary bypass.

作者信息

Sheil Meredith L, Luxford Catherine, Davies Michael J, Peat Jennifer K, Nunn Graham, Celermajer David S

机构信息

Adolph Basser Cardiac Institute, The Children's Hospital at Westmead, Sydney, Australia.

出版信息

J Thorac Cardiovasc Surg. 2005 Oct;130(4):1054-61. doi: 10.1016/j.jtcvs.2005.03.048.

DOI:10.1016/j.jtcvs.2005.03.048

PMID:16214520

Abstract

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.

摘要

目的

蛋白质是生物结构和功能的主要效应分子。氧化诱导的蛋白质结构变化会严重损害蛋白质功能，并产生重要的病理后果。本研究旨在探讨小儿体外循环期间是否会发生氧化诱导的蛋白质结构变化，并研究其与术后结局的相关性。

方法

蛋白质中3,4-二羟基苯丙氨酸含量相对于其天然酪氨酸含量的升高表明存在氧化导致的结构损伤。在24例接受先天性心脏病修复手术的儿童中，前瞻性地选择形成一个青紫组和一个可比的非青紫对照组，于手术前及开始体外循环后长达6小时测量蛋白质3,4-二羟基苯丙氨酸/天然酪氨酸比值。结果与围手术期变量和术后结局相关。

结果

青紫组儿童在开始体外循环后30分钟内蛋白质3,4-二羟基苯丙氨酸/酪氨酸比值高于基线水平（0.48 mmol/mol [标准差，0.11 mmol/mol] 对 0.36 mmol/mol [标准差，0.13 mmol/mol]；P = 0.001），而非青紫组儿童未出现此情况，且该比值与术前动脉血氧饱和度呈负相关（R = -0.52；P = 0.03）。在接受长时间手术的儿童中，体外循环开始后120分钟（0.44 mmol/mol [标准差，0.12 mmol/mol]；P = 0.007）和180分钟（0.40 mmol/mol [标准差，0.14 mmol/mol]；P = 0.01）时，蛋白质3,4-二羟基苯丙氨酸/酪氨酸比值也高于基线水平。长时间手术期间3,4-二羟基苯丙氨酸/酪氨酸比值升高与术后心律失常以及需要增加正性肌力支持相关（P = 0.001）。