Morita K, Ihnken K, Buckberg G D, Matheis G, Sherman M P, Young H H
Department of Surgery, University of California, Los Angeles School of Medicine 90095-1741, USA.
J Thorac Cardiovasc Surg. 1995 Oct;110(4 Pt 2):1245-54. doi: 10.1016/s0022-5223(95)70011-0.
This study tests the hypothesis that reoxygenation of cyanotic immature hearts when starting cardiopulmonary bypass produces an "unintended" reoxygenation injury that (1) nullifies the cardioprotective effects of blood cardioplegia and (2) is avoidable by adding antioxidants N-(2-mercaptopropionyl)-glycine plus catalase to the cardiopulmonary bypass prime. Twenty immature piglets (2 to 3 weeks) underwent 30 minutes of aortic clamping with a blood cardioplegic solution that was hypocalcemic, alkalotic, hyperosmolar, and enriched with glutamate and aspartate during 1 hour of cardiopulmonary bypass. Of these, six piglets did not undergo hypoxemia (blood cardioplegic control) and 14 others remained hypoxemic (oxygen tension about 25 mm Hg) for up to 2 hours by lowering ventilator fraction of inspired oxygen before reoxygenation on cardiopulmonary bypass. The primary solution of the cardiopulmonary bypass circuit was unchanged in eight piglets (no treatment) and supplemented with the antioxidants N-(2-mercaptopropionyl)-glycine (80 mg/kg) and catalase (5 mg/kg) in six others (N-(2-mercaptopropionyl)-glycine and catalase). Myocardial function (end-systolic elastance), lipid peroxidation (myocardial conjugated diene production), and antioxidant reserve capacity were evaluated. Blood cardioplegic arrest produced no biochemical or functional changes in nonhypoxemic control piglets. Reoxygenation caused an approximate 10-fold increase in conjugated production that persisted throughout cardiopulmonary bypass, lowered antioxidant reserve capacity 86% +/- 12%, and produced profound myocardial dysfunction, because end-systolic elastance recovered only 21% +/- 2%. Supplementation of the cardiopulmonary bypass prime with N-(2-mercaptopropionyl)-glycine and catalase reduced lipid peroxidation, restored antioxidant reserve capacity, and allowed near complete functional recovery (80% +/- 8%).** Lipid peroxidation (conjugated diene) production was lower during warm blood cardioplegic reperfusion than during induction in all reoxygenated hearts, which suggests that blood cardioplegia did not injure reoxygenated myocardium. We conclude that reoxygenation of the hypoxemic immature heart causes cardiac functional and antioxidant damage that nullifies the cardioprotective effects of blood cardioplegia that can be avoided by supplementation of the cardiopulmonary bypass prime with antioxidants (*p < 0.05 vs blood cardioplegic control; **p < 0.05 vs reoxygenation).
在开始体外循环时，青紫未成熟心脏的复氧会产生一种“意外的”复氧损伤，这种损伤（1）会抵消血液停搏液的心脏保护作用，（2）通过在体外循环预充液中添加抗氧化剂N-（2-巯基丙酰基）-甘氨酸加过氧化氢酶可避免。20只未成熟仔猪（2至3周龄）在体外循环1小时期间，用一种低钙、碱性、高渗且富含谷氨酸和天冬氨酸的血液停搏液进行了30分钟的主动脉钳夹。其中，6只仔猪未经历低氧血症（血液停搏液对照），另外14只在体外循环复氧前通过降低呼吸机吸入氧分数，保持低氧血症状态（氧分压约25 mmHg）长达2小时。8只仔猪的体外循环回路主溶液未改变（未治疗），另外6只在体外循环回路主溶液中添加了抗氧化剂N-（2-巯基丙酰基）-甘氨酸（80 mg/kg）和过氧化氢酶（5 mg/kg）（N-（2-巯基丙酰基）-甘氨酸和过氧化氢酶）。评估了心肌功能（收缩末期弹性）、脂质过氧化（心肌共轭二烯生成）和抗氧化储备能力。血液停搏液心脏停搏在非低氧血症对照仔猪中未引起生化或功能变化。复氧导致共轭生成增加约10倍，在整个体外循环过程中持续存在，使抗氧化储备能力降低86%±12%，并导致严重的心肌功能障碍（收缩末期弹性仅恢复21%±2%）。在体外循环预充液中添加N-（2-巯基丙酰基）-甘氨酸和过氧化氢酶可减少脂质过氧化，恢复抗氧化储备能力，并使功能近乎完全恢复（80%±8%）。**在所有复氧心脏中，温血停搏液再灌注期间的脂质过氧化（共轭二烯）生成低于诱导期间，这表明血液停搏液不会损伤复氧心肌。我们得出结论，低氧未成熟心脏的复氧会导致心脏功能和抗氧化损伤，从而抵消血液停搏液的心脏保护作用，通过在体外循环预充液中添加抗氧化剂可避免这种情况（*与血液停搏液对照相比，p<0.05；**与复氧相比，p<0.05）。
