From the Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (N.S.F., C.S.S., F.F.C., N.N.R., M.V.S.F., J.A.M., R.L.B.-M., P.L.S., P.R.M.R.) the Department of Physiology and Pharmacology, Biomedical Institute, Fluminense Federal University, Niteroi, Brazil (N.N.R.) the Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil (V.L.C.) the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy (P.P.) Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Martino, Genoa, Italy (P.P.) Regions Hospital and University of Minnesota, Minneapolis/Saint Paul, Minnesota (J.J.M.).
Anesthesiology. 2019 May;130(5):767-777. doi: 10.1097/ALN.0000000000002630.
This study hypothesized that, in experimental mild acute respiratory distress syndrome, lung damage caused by high tidal volume (VT) could be attenuated if VT increased slowly enough to progressively reduce mechanical heterogeneity and to allow the epithelial and endothelial cells, as well as the extracellular matrix of the lung to adapt. For this purpose, different strategies of approaching maximal VT were tested.
Sixty-four Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, animals were randomly assigned to receive mechanical ventilation with VT = 6 ml/kg for 2 h (control); VT = 6 ml/kg during hour 1 followed by an abrupt increase to VT = 22 ml/kg during hour 2 (no adaptation time); VT = 6 ml/kg during the first 30 min followed by a gradual VT increase up to 22 ml/kg for 30 min, then constant VT = 22 ml/kg during hour 2 (shorter adaptation time); and a more gradual VT increase, from 6 to 22 ml/kg during hour 1 followed by VT = 22 ml/kg during hour 2 (longer adaptation time). All animals were ventilated with positive end-expiratory pressure of 3 cm H2O. Nonventilated animals were used for molecular biology analysis.
At 2 h, diffuse alveolar damage score and heterogeneity index were greater in the longer adaptation time group than in the control and shorter adaptation time animals. Gene expression of interleukin-6 favored the shorter (median [interquartile range], 12.4 [9.1-17.8]) adaptation time compared with longer (76.7 [20.8 to 95.4]; P = 0.02) and no adaptation (65.5 [18.1 to 129.4]) time (P = 0.02) strategies. Amphiregulin, metalloproteinase-9, club cell secretory protein-16, and syndecan showed similar behavior.
In experimental mild acute respiratory distress syndrome, lung damage in the shorter adaptation time group compared with the no adaptation time group was attenuated in a time-dependent fashion by preemptive adaptation of the alveolar epithelial cells and extracellular matrix. Extending the adaptation period increased cumulative power and did not prevent lung damage, because it may have exposed animals to injurious strain earlier and for a longer time, thereby negating any adaptive benefit.
本研究假设，在实验性轻度急性呼吸窘迫综合征中，如果潮气量（VT）增加的速度足够慢，以逐渐降低机械异质性，并允许肺的上皮细胞和内皮细胞以及细胞外基质适应，那么由大潮气量引起的肺损伤可以减轻。为此，测试了几种接近最大 VT 的策略。
64 只 Wistar 大鼠接受大肠杆菌脂多糖气管内给药。24 小时后，动物随机分为以下几组：接受 VT=6ml/kg 的机械通气 2 小时（对照组）；VT=6ml/kg 持续 1 小时，然后在第 2 小时突然增加至 VT=22ml/kg（无适应时间）；VT=6ml/kg 持续 30 分钟，然后逐渐增加至 22ml/kg 持续 30 分钟，然后在第 2 小时持续 VT=22ml/kg（较短适应时间）；以及更逐渐的 VT 增加，从第 1 小时的 6 至 22ml/kg，然后在第 2 小时持续 VT=22ml/kg（较长适应时间）。所有动物均给予呼气末正压 3cmH2O。未通气的动物用于分子生物学分析。
在 2 小时时，较长适应时间组的弥漫性肺泡损伤评分和异质性指数均高于对照组和较短适应时间组。白细胞介素 6 的基因表达偏向于较短的（中位数[四分位数范围]，12.4[9.1-17.8]）适应时间，而不是较长（76.7[20.8 至 95.4]）和无适应（65.5[18.1 至 129.4]）时间（P=0.02）策略。 Amphiregulin、金属蛋白酶 9、club 细胞分泌蛋白 16 和 syndecan 表现出相似的行为。
在实验性轻度急性呼吸窘迫综合征中，与无适应时间组相比，较短适应时间组的肺损伤在肺泡上皮细胞和细胞外基质的预先适应作用下，呈时间依赖性减轻。延长适应期会增加累积功率，并且不能防止肺损伤，因为它可能使动物更早且更长时间地暴露于损伤应变下，从而否定任何适应性益处。
