Sage Michaël, See Wendy, Nault Stéphanie, Morin Christophe, Michalski Christina, Chabot Benoit, Marouan Sofia, Lavoie Pascal M, Micheau Philippe, Praud Jean-Paul, Fortin-Pellerin Étienne
Department of Pharmacology-Physiology, Université de Sherbrooke, Sherbrooke, QC, Canada.
BC Children's Hospital Research Institute, The University of British Columbia, Vancouver, BC, Canada.
Front Physiol. 2020 Jun 18;11:603. doi: 10.3389/fphys.2020.00603. eCollection 2020.
Animal experiments suggest that total liquid ventilation (TLV) induces less ventilator-induced lung injury (VILI) than conventional mechanical gas ventilation. However, TLV parameters that optimally minimize VILI in newborns remain unknown. Our objective was to compare lung inflammation between low (L-V) and high (H-V) liquid tidal volume and evaluate impacts on the weaning process. Sixteen anesthetized and paralyzed newborn lambs were randomized in an L-V group (initial tidal volume of 10 mL/kg at 10/min) and an H-V group (initial tidal volume of 20 mL/kg at 5/min). Five unventilated newborn lambs served as controls. After 4 h of TLV in the supine position, the lambs were weaned in the prone position for another 4 h. The levels of respiratory support needed during the 4 h post-TLV were compared. The anterior and posterior lung regions were assessed by a histological score and real-time quantitative PCR for , , and plus 12 other exploratory VILI-associated genes. All but one lamb were successfully extubated within 2 h post-TLV (72 ± 26 min vs. 63 ± 25 min, = 0.5) with similar FiO at 4 h post-TLV (27 ± 6% vs. 33 ± 7%, = 0.3) between the L-V and H-V lambs. No significant differences were measured in histological inflammation scores between L-V and H-V lambs, although lambs in both groups exhibited slightly higher scores than the control lambs. The L-V group displayed higher mRNA expression than the H-V group in both anterior (2.8 ± 1.5-fold increase vs. 1.3 ± 0.4-fold increase, = 0.02) and posterior lung regions (3.0 ± 1.0-fold change increase vs. 1.1 ± 0.3-fold increase, = 0.002), respectively. No significant differences were found in and expression levels. Gene expression changes overall indicated that L-V was associated with a qualitatively distinct inflammatory gene expression profiles compared to H-V, which may indicate different clinical effects. In light of these findings, further mechanistic studies are warranted. In conclusion, we found no advantage of lower tidal volume use, which was in fact associated with a slightly unfavorable pattern of inflammatory gene expression.
动物实验表明，与传统机械气体通气相比，全液体通气（TLV）引起的呼吸机诱导性肺损伤（VILI）更少。然而，能使新生儿VILI降至最低的最佳TLV参数仍不清楚。我们的目的是比较低（L-V）和高（H-V）液体潮气量时的肺部炎症，并评估其对撤机过程的影响。将16只麻醉并麻痹的新生羔羊随机分为L-V组（初始潮气量为10 mL/kg，频率为10次/分钟）和H-V组（初始潮气量为20 mL/kg，频率为5次/分钟）。5只未通气的新生羔羊作为对照。仰卧位进行4小时TLV后，羔羊转为俯卧位再进行4小时撤机。比较TLV后4小时所需的呼吸支持水平。通过组织学评分以及对 、 和 加上其他12个与VILI相关的探索性基因进行实时定量PCR，评估肺的前后区域。除一只羔羊外，所有羔羊在TLV后2小时内成功拔管（72±26分钟对63±25分钟，P = 0.5），L-V组和H-V组羔羊在TLV后4小时的FiO 相似（27±6%对33±7%，P = 0.3）。L-V组和H-V组羔羊的组织学炎症评分无显著差异，尽管两组羔羊的评分均略高于对照羔羊。L-V组在前肺区域（增加2.8±1.5倍对增加1.3±0.4倍，P = 0.02）和后肺区域（变化增加3.0±1.0倍对增加1.1±0.3倍，P = 0.002）的 mRNA表达均高于H-V组。 和 的表达水平无显著差异。总体基因表达变化表明，与H-V相比，L-V与性质不同的炎症基因表达谱相关，这可能表明临床效果不同。鉴于这些发现，有必要进行进一步的机制研究。总之，我们发现较低潮气量并无优势，实际上它与炎症基因表达的轻微不利模式相关。
