Lee Tze-fun, Tymafichuk Corinne N, Schulz Richard, Cheung Po-Yin
Department of Pediatrics, University of Alberta, NICU Royal Alexandra Hospital, Edmonton, Alberta T5H 3V9, Canada.
Intensive Care Med. 2009 Sep;35(9):1628-35. doi: 10.1007/s00134-009-1553-x. Epub 2009 Jun 24.
Significant improvement in myocardial recovery has been shown previously with interventions to decrease reactive oxygen species after ischemia/hypoxia. We investigated whether co-administration of N-acetylcysteine (NAC, a scavenger for reactive oxygen species) and N (G)-monomethyl-L: -arginine (L-NMMA, a non-selective nitric oxide synthase inhibitor) results in better hemodynamic recovery.
Controlled, block-randomized study.
University research laboratory.
Mixed breed piglets (1-4d, 1.6-2.4 kg).
Acutely instrumented piglets received normocapnic alveolar hypoxia (10-15% oxygen) for 2 h followed by reoxygenation with 100% oxygen (1 h) then 21% oxygen (3 h). After reoxygenation, hypoxic-reoxygenated piglets were given either saline (controls), NAC [30 mg/kg bolus + 20 mg/(kg h) infusion], NMMA [0.1 mg/kg bolus + 0.1 mg/(kg h) infusion] or NAC + L-NMMA via intravenous infusion in a blinded, randomized fashion (n = 8/group). Sham-operated piglets had no hypoxia-reoxygenation (n = 5).
Both cardiac index and stroke volume of hypoxia-reoxygenation controls remained depressed during reoxygenation (vs. normoxic baseline, p < 0.05). Post-resuscitation treatment with L-NMMA alone did not improve systemic hemodynamic recovery, but caused pulmonary hypertension (vs. controls). In contrast, treating the piglets with either NAC or NAC + L-NMMA improved cardiac index and stroke volume, with no effect on heart rate and blood pressure (vs. controls). These treatments also decreased various oxidative stress markers in myocardial tissues (vs. controls). However, there was no significant difference between NAC- and NAC + L-NMMA groups in all examined parameters.
Post-resuscitation administration of NAC improved cardiac function and reduced oxidative stress in newborn pigs with hypoxia-reoxygenation insult. Low-dose, non-selective inhibitor of nitric oxide synthase activity did not provide any further beneficial effect.
先前的研究表明，通过干预措施减少缺血/缺氧后的活性氧，心肌恢复有显著改善。我们研究了联合使用N-乙酰半胱氨酸（NAC，一种活性氧清除剂）和N（G）-单甲基-L-精氨酸（L-NMMA，一种非选择性一氧化氮合酶抑制剂）是否能带来更好的血流动力学恢复。
对照、区组随机研究。
大学研究实验室。
杂种仔猪（1 - 4日龄，体重1.6 - 2.4千克）。
对急性植入仪器的仔猪进行常碳酸血症性肺泡缺氧（10 - 15%氧气）2小时，随后用100%氧气复氧1小时，再用21%氧气复氧3小时。复氧后，对缺氧复氧仔猪以盲法、随机方式静脉输注生理盐水（对照组）、NAC[30毫克/千克推注 + 20毫克/（千克·小时）输注]、L-NMMA[0.1毫克/千克推注 + 0.1毫克/（千克·小时）输注]或NAC + L-NMMA（每组n = 8）。假手术仔猪未进行缺氧复氧（n = 5）。
缺氧复氧对照组在复氧期间心脏指数和每搏输出量均持续降低（与正常氧合基线相比，p < 0.05）。单独使用L-NMMA进行复苏后治疗并未改善全身血流动力学恢复，但导致了肺动脉高压（与对照组相比）。相比之下，用NAC或NAC + L-NMMA治疗仔猪可改善心脏指数和每搏输出量，对心率和血压无影响（与对照组相比）。这些治疗还降低了心肌组织中的各种氧化应激标志物（与对照组相比）。然而，NAC组和NAC + L-NMMA组在所有检测参数上均无显著差异。
对缺氧复氧损伤的新生仔猪进行复苏后给予NAC可改善心脏功能并降低氧化应激。低剂量、非选择性一氧化氮合酶活性抑制剂未提供任何进一步的有益效果。
