Morita K, Ihnken K, Buckberg G D, Sherman M P, Young H H, Ignarro L J
Department of Surgery, School of Medicine University of California, Los Angeles 90024.
J Clin Invest. 1994 Jun;93(6):2658-66. doi: 10.1172/JCI117279.
Cardiopulmonary bypass (CPB) is used increasingly to correct cyanotic heart defects during early infancy, but myocardial dysfunction is often seen after surgical repair. This study evaluates whether starting CPB at a conventional, hyperoxic pO2 causes an "unintentional" reoxygenation (ReO2) injury. We subjected 2-wk-old piglets to ventilator hypoxemia (FIO2 approximately 0.06, pO2 approximately 25 mmHg) followed by 5 min of ReO2 on CPB before instituting cardioplegia. CPB was begun in hypoxemic piglets by either abrupt ReO2 at a pO2 of 400 mmHg (standard clinical practice) or by maintaining pO2 approximately 25 mmHg on CPB until controlling ReO2 with blood cardioplegic arrest. The effects of abrupt vs. gradual ReO2 without surgical ischemia (blood cardioplegia) were also compared. Myocardial nitric oxide (NO) production (chemiluminescence measurements of NO2- + NO3-) and conjugated diene (CD) generation (spectrophotometric A233 measurements of lipid extracts) using aortic and coronary sinus blood samples were assessed during cardioplegic induction. 30 min after CPB, left ventricular end-systolic elastance (Ees, catheter conductance method) was used to determine cardiac function. CPB and blood cardioplegic arrest caused no functional or biochemical change in normoxic (control) hearts. Abrupt ReO2 caused a depression of myocardial function (Ees = 25 +/- 5% of control). Functional depression was relatively unaffected by gradual ReO2 without blood cardioplegia (34% recovery of Ees), and abrupt ReO2 immediately before blood cardioplegia caused a 10-fold rise in cardiac NO and CD production, with subsequent depression of myocardial function (Ees 21 +/- 2% of control). In contrast, controlled cardiac ReO2 reduced NO production 94%, CD did not rise, and Ees was 83 +/- 8% of normal. We conclude ReO2 injury is related to increased NO production during abrupt ReO2, nullifies the cardioprotective effects of blood cardioplegia, and that controlled cardiac ReO2 when starting CPB to correct cyanotic heart defects may reduce NO production and improve myocardial status postoperatively.
体外循环（CPB）越来越多地用于纠正婴儿早期的青紫型心脏缺陷，但手术修复后常出现心肌功能障碍。本研究评估在常规高氧pO₂开始体外循环是否会导致“无意的”再氧合（ReO₂）损伤。我们将2周龄仔猪置于呼吸机低氧血症状态（FIO₂约为0.06，pO₂约为25 mmHg），然后在进行心脏停搏之前在体外循环上进行5分钟的再氧合。低氧血症仔猪通过在pO₂为400 mmHg时突然再氧合（标准临床实践）或在体外循环上维持pO₂约25 mmHg直至通过血液心脏停搏控制再氧合来开始体外循环。还比较了无手术缺血（血液心脏停搏）时突然与逐渐再氧合的效果。在心脏停搏诱导期间，使用主动脉和冠状窦血样评估心肌一氧化氮（NO）产生（NO₂⁻ + NO₃⁻的化学发光测量）和共轭二烯（CD）生成（脂质提取物的分光光度法A₂₃₃测量）。体外循环30分钟后，使用左心室收缩末期弹性（Ees，导管电导法）来确定心脏功能。体外循环和血液心脏停搏在常氧（对照）心脏中未引起功能或生化变化。突然再氧合导致心肌功能下降（Ees =对照的25±5%）。无血液心脏停搏的逐渐再氧合对功能下降的影响相对较小（Ees恢复34%），而在血液心脏停搏前立即突然再氧合导致心脏NO和CD产生增加10倍，随后心肌功能下降（Ees为对照的21±2%）。相比之下，控制性心脏再氧合使NO产生减少94%，CD未升高，Ees为正常的83±8%。我们得出结论，再氧合损伤与突然再氧合期间NO产生增加有关，抵消了血液心脏停搏的心脏保护作用，并且在开始体外循环以纠正青紫型心脏缺陷时进行控制性心脏再氧合可能会减少NO产生并改善术后心肌状态。
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