Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
Crit Care Med. 2013 Apr;41(4):1069-74. doi: 10.1097/CCM.0b013e3182746704.
Cardiovascular dysfunction occurs in the majority of asphyxiated neonates and has been suggested to be a major cause of neonatal morbidity and mortality. We previously demonstrated that cyclosporine A treatment during resuscitation can significantly improve cardiovascular performance in asphyxiated newborn piglets. However, the mechanisms through which cyclosporine elicits its protective effect in neonates have not yet been fully characterized. We hypothesized that cyclosporine A treatment would attenuate myocardial and cardiac mitochondrial injury during the resuscitation of asphyxiated newborn piglets.
After acute instrumentation, piglets received normocapnic alveolar hypoxia (10% to 15% oxygen) for 2 hours followed by reoxygenation with 100% oxygen (0.5 hr) and then 21% oxygen (3.5 hr). At 4 hours of reoxygenation, plasma troponin level, left ventricle myocardial levels of lipid hydroperoxides, cytochrome-c, and mitochondrial aconitase activity were determined.
Neonatal asphyxia and reoxygenation.
Twenty-four newborn (1-4 days old) piglets.
Piglets were randomized to receive an IV bolus of cyclosporine A (10 mg/kg) or normal saline (placebo, control) at 5 minutes of reoxygenation (n=8/group). Sham-operated piglets (n=8) underwent no asphyxia-reoxygenation.
Asphyxiated piglets treated with cyclosporine had lower plasma troponin and myocardial lipid hydroperoxides levels (vs. controls, both p<0.05, analysis of variance). Cyclosporine treatment also improved mitochondrial aconitase activity and attenuated the rise in cytosol cytochrome-c level (vs. controls, all p<0.05). The improved mitochondrial function significantly correlated with cardiac output (p<0.05, Spearman rank-correlation test).
We demonstrate that the postresuscitation administration of cyclosporine attenuates myocardial and cardiac mitochondrial injury in asphyxiated newborn piglets following resuscitation.
心血管功能障碍发生在大多数窒息的新生儿中，被认为是新生儿发病率和死亡率的主要原因。我们之前的研究表明，复苏过程中给予环孢素 A 治疗可显著改善窒息新生仔猪的心血管功能。然而，环孢素在新生儿中发挥保护作用的机制尚未得到充分阐明。我们假设环孢素 A 治疗可减轻窒息新生仔猪复苏过程中心肌和心脏线粒体损伤。
急性仪器操作后，猪接受正常碳酸肺泡缺氧（10%至 15%氧气）2 小时，然后用 100%氧气（0.5 小时）和 21%氧气（3.5 小时）再氧合。在再氧合 4 小时时，测定血浆肌钙蛋白水平、左心室心肌脂质过氧化物、细胞色素-c 和线粒体 aconitase 活性。
新生儿窒息和再氧合。
24 只新生（1-4 天龄）猪。
猪在再氧合 5 分钟时随机接受环孢素 A（10mg/kg）静脉推注或生理盐水（安慰剂，对照）（n=8/组）。假手术猪（n=8）未进行窒息-再氧合。
接受环孢素治疗的窒息猪的血浆肌钙蛋白和心肌脂质过氧化物水平较低（与对照组相比，均 p<0.05，方差分析）。环孢素治疗还改善了线粒体 aconitase 活性并减轻了胞浆细胞色素-c 水平的升高（与对照组相比，均 p<0.05）。改善的线粒体功能与心输出量显著相关（p<0.05，Spearman 秩相关检验）。
我们证明，复苏后给予环孢素可减轻窒息新生仔猪再氧合后心肌和心脏线粒体损伤。
