神经调节辅助通气对急性呼吸窘迫综合征兔呼吸机相关性膈肌功能障碍的影响

Effects of neurally adjusted ventilatory assist on prevention of ventilator-induced diaphragmatic dysfunction in acute respiratory distress syndrome rabbits

目的 探讨神经调节辅助通气（NAVA）对ARDS呼吸机相关性膈肌功能障碍（VIDD）的预防作用.方法 将20只成年新西兰大白兔按随机数字表法分为对照组、容量控制通气组（VC组）、压力支持通气组（PSV组）和NAVA通气组（NAVA组）,每组5只.VC、PSV及NAVA组在机械通气4 h后取膈肌标本,对照组麻醉后立即取膈肌标本.测定各组膈肌中丙二醛、超氧化物歧化酶（SOD）以及还原型谷胱甘肽（GSH）含量,观察各组膈肌纤维病理结构的改变.结果 （1）丙二醛：NAVA组膈肌中丙二醛含量为（0.28±0.19）nmol/mg,与对照组的（0.15±0.06）nmol/mg、PSV组的（0.30±0.11）nmol/mg比较,差异无统计学意义（F=2.730,P＞0.05）;VC组膈肌中丙二醛含量为（0.40±0.16）nmol/mg,明显高于对照组（P＜0.05）.（2）SOD：NAVA组膈肌中SOD含量为（94±9）U/mg,与对照组的（111±12）U/mg、PSV组的（93±4）U/mg比较,差异无统计学意义（F=4.422,P＞0.05）;VC组膈肌中SOD含量为（80±21）U/mg,明显低于对照组（P＜0.05）.（3）GSH：NAVA组膈肌中丙二醛含量为（5.6±1.0）mg/g,与对照组的（5.3±1.0）mg/g、PSV组的（4.5±1.2）mg/g比较,差异无统计学意义（F=3.001,P＞0.05）;VC组膈肌中GSH含量为（3.3±1.7）mg/g,明显低于对照组（P＜0.05）.（4）光镜观察：VC组出现肌纤维变性、坏死,部分肌纤维萎缩;NAVA、PSV组以及对照组肌纤维形态基本正常.（5）电镜观察：VC组肌原纤维断裂,线粒体肿胀;NAVA组、PSV组以及对照组超微结构无明显异常.（6）膈肌纤维横截面积：NAVA组平均肌纤维横截面积（像素）为2573±278,与对照组的3070＋175、PSV组的2508±670比较,差异无统计学意义（F=1.775,P＞0.05）;VC组Ⅱ型肌纤维横截面积为2210±971,明显低于对照组的3477±187（P＜0.05）.结论 与控制通气相比较,NAVA可减轻ARDS膈肌氧化应激、膈肌萎缩和膈肌结构损伤,NAVA较控制通气更能预防VIDD.

Objective To evaluate the effect of neurally adjusted ventilatory assist （NAVA） on prevention of ventilator-induced diaphragmatic dysfunction （VIDD） in ARDS rabbits.Methods Twenty New Zealand white rabbits were randomly divided into 4 groups： （ 1 ） control group （ n = 5 ）; （ 2 ） Volume control （VC） group （ n = 5 ）; （ 3 ） Pressure support （ PSV ） group （ n = 5 ）; （4） NAVA group （ n = 5 ）.In VC, PSV and NAVA groups, the rabbits were killed and the diaphragm was removed after 4 hours of ventilation.Animals in the control group were not mechanically ventilated, and the diaphragm was also removed immediately after anesthetizing.In all rabbits, malondialdehyde （ MDA）, superoxide disrmutase （SOD） and glutathione（GSH） of diaphragm were measured.Structure of diaphragm was observed by light microscope, electron microscope, constituent ratio and mean cross-sectional area （CSA） of diaphragm fiber.Results （1）MDA： Compared with the control [（0.15 ±0.06）nmol/mg], PSV group[（0.30 ±0.11）nmol/mg], there was no significant difference in MDA of diaphragm in NAVA group [（ 0.28 ± 0.19 ）nmol/mg] （F = 2.730, P 〉 0.05）.MDA in VC group [（0.40 ±0.16）nmol/mg] was significantly higher than the control group （P〈0.05）.（2） SOD： Compared with control [（ 111 ± 12） U/mg], PSV group [（93 ± 4） U/mg], there was no significant difference in SOD of diaphragm in NAVA group [（ 94 ± 9 ）U/mg] （F=4.422,P 〉0.05）.SOD in VC group [（80 ±21 ）U/mg] was significantly lower than the control group（P 〈0.05）.（3）GSH： Compared with control [（5.3 ± 1.0）mg/g] and PSV group [（4.5 ±1.2）mg/g], there was no significant difference in GSH of diaphragm in NAVA group [（5.6 ± 1.0） mg/g]（F =3.001 ,P 〉 0.05 ）.GSH in VC group [（3.3 ± 1.7）mg/g] is significantly lower than control and NAVA groups （ P 〈 0.05 ）.（ 4 ） Light microscope： In VC group, many changes were observed in the muscle, such as myofibrosis, necrosis, and some of muscle fibers became atrophy, but these were no obvious changes of pathological structure in control, PSV or NAVA groups.（5）Electron microscope： In control, PSV and NAVA groups, the ultrastructure of diaphragm was normal Different from the above 3 groups, some abnormal ultrastructure was observed in VC group, including disrupted myofibrils, swollen mitochondria.（6）CSA of diaphragm fiber： Compared with control and PSV group, there was no significant difference in CSA of diaphragm fiber in NAVA group （ P 〉 0.05 ）; The CSA of type Ⅱ fibers in VC group was markedly lower than control group （ P 〈 0.05 ） .Conclusions Compared with volume control ventilation, NAVA may mitigate diaphragmatic oxidative stress, atrophy and injury, and prevent VIDD better than VC.