Department of Experimental Anaesthesiology, Chair of Anaesthesiology and Intensive Therapy, Poznan University of Medical Sciences, 14, Sw. Marii Magdaleny st., 61-861, Poznan, Poland.
Department of Animal Physiology and Biochemistry, Poznan University of Life Sciences, 33, Wolynska st., 60-637, Poznan, Poland.
Sci Rep. 2019 Jan 24;9(1):569. doi: 10.1038/s41598-018-37090-9.
Nitric oxide (NO) generation by systemic neonatal neutrophils is not clarified. It is also not known whether local anaesthetics (LAs) transferred to the fetal systemic circulation following maternal epidural blockade may affect this process. In the present study, NO generation was evaluated in neutrophils from cord blood (CB, n = 11) and adult blood (n = 10) following exposure to bupivacaine (0.0005, 0.005, 1 mM), lidocaine (0.002, 0.02, 4 mM) and ropivacaine (0.0007, 0.007, 1.4 mM) using flow cytometry, as well as indirectly by determining nitrite concentrations in cell incubation media. To determine the role of NO synthase (NOS) isoforms in NO generation following exposure to LAs, experiments were repeated in the presence of the NOS inhibitors, N-nitro-L-arginine methyl ester and aminoguanidine; in addition, the expression of NOS isoforms was analysed. CB neutrophils produced less NO than adult neutrophils. LAs, especially ropivacaine and lidocaine, stimulated neutrophil NO generation, but in CB neutrophils this effect was negligible at clinically relevant drug concentrations. A mechanism involving NOS activity was responsible for the observed phenomena. In conclusion, LAs are able to upregulate neutrophil NO production, but in neonates this effect is likely to be clinically insignificant.
尚未阐明新生儿全身中性粒细胞产生一氧化氮（NO）的情况。也不知道母体硬膜外阻滞后转移到胎儿全身循环的局部麻醉剂（LAs）是否会影响这一过程。在本研究中，通过流式细胞术评估了暴露于布比卡因（0.0005、0.005 和 1mM）、利多卡因（0.002、0.02 和 4mM）和罗哌卡因（0.0007、0.007 和 1.4mM）后，脐血（CB，n=11）和成人血液（n=10）中性粒细胞中的 NO 生成情况，以及通过测定细胞孵育介质中硝酸盐浓度间接评估。为了确定一氧化氮合酶（NOS）同工型在暴露于 LAs 后产生 NO 的作用，在存在 NOS 抑制剂 N-硝基-L-精氨酸甲酯和氨基胍的情况下重复了实验；此外，还分析了 NOS 同工型的表达。CB 中性粒细胞产生的 NO 少于成人中性粒细胞。LAs，尤其是罗哌卡因和利多卡因，刺激中性粒细胞产生 NO，但在临床相关药物浓度下，CB 中性粒细胞的这种作用可以忽略不计。涉及 NOS 活性的机制是导致观察到的现象的原因。总之，LAs 能够上调中性粒细胞的 NO 产生，但在新生儿中，这种作用可能在临床上无足轻重。
