长期机械通气患者膈肌功能的超声评估研究

目的 明确影响长期机械通气患者膈肌功能变化的原因.方法 选择解放军总医院呼吸科2018年6月1日到2019年4月30日的机械通气患者(32例).将入组的患者按机械通气时间分为短期机械通气组(7 d≤机械通气时间＜1个月,20例)和长期机械通气组(机械通气时间≥1个月,12例).比较两组患者膈肌的运动幅度、收缩时间、收缩...     

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

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.

Abstract：

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.     

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

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.     

耐力运动锻炼对肺气肿大鼠膈肌功能的影响

目的 观察运动锻炼对肺气肿大鼠膈肌收缩与代谢功能的影响。方法 ＳＤ大鼠,随机分肺气肿组,经气管内一次性滴注猪胰弹性蛋白酶８００Ｕ／ｋｇ;正常组,一次性气管内滴注体积０．９％氯化钠溶液;４周后再随机分为正常对照组、正常运动组、肺气肿对照组和肺气肿运动组;对正常运动组和肺气肿运动组实施同等强度〖最大氧耗量（ＶＯ２ｍａｘ）５５％～７５％〗和时间（１２周）的电动平板跑步锻炼。结果 与其他组比较,肺气肿运动     

机械通气对膈肌形态和功能影响的实验研究进展

在上个世纪50年代的脊髓灰质炎爆发流行中，机械通气（mechanical ventilation,MV）的引入挽救了许多呼吸肌麻痹患者的生命，从那时起，机械通气已成为处理呼吸泵衰竭或气体交换障碍患者的必备手段，但有大约30%的MV患者出现脱机困难。脱机困难的病理生理机制目前还不清楚，但越来越多的证据表明MV本身可导致吸气肌（主要是膈肌）功能和形态的改变，这些改变可能是引起MV脱机困难的重要原因。     

机械通气时间对机械通气撤机患者膈肌功能的影响分析

目的 探讨机械通气时间对机械通气患者膈肌功能的影响.方法 以2008年12月至2009年12月入住东南大学附属中大医院ICU行机械通气超过24 h,且准备撤机的患者为研究对象,根据机械通气时间分为机械通气≤3d组(A组)及机械通气＞3d组(B组).行自主呼吸实验(SBT)30 min,监测SBT 0、5及30 min时膈肌电位(Edi)、神经肌肉强度指数(NMS)、神经机械耦连指数(NMC)及神经通气耦连指数(NVC)等膈肌功能指标.结果 44例患者纳入研究,A组患者25例(56.8％),B组患者19例(43.2％).①SBT 0 min时A、B两组患者间Edi、NMS、NMC及NVC差异均无统计学意义.②SBT 5 min时B组患者Edi和NMS显著高于A组.③SBT 30 min时B组患者Edi显著高于A组[(23±11)μV比(15±8)μV,P＜0.05];与A组患者NMS相比,B组患者NMS显著增高[(598±309)μV· cpm比(363±224)μV·cpm](P＜0.05),而B组患者NVC则明显低于A组.结论 SBT 30 min时机械通气＞3 d的患者膈肌收缩能力、耐力均下降;提示机械通气时间增加可能是导致膈肌功能下降的重要原因.     

国内慢性阻塞性肺疾病患者有创机械通气撤机应用膈肌超声诊断价值的Meta分析

目的:评价膈肌超声预测国内慢性阻塞性肺疾病(COPD)患者有创机械通气撤机的临床诊断价值。方法:检索PubMed、Embase、Cochrane Library、Web of Science、中国生物医学文献服务系统、中国知网、万方、维普等数据库,截至2019年12月31日,以英文或中文出版的文献。筛选符合纳入条件的研...     

膈肌功能评价在机械通气撤机中的应用进展

机械通气撤机目前仍然是困扰临床医师的一大难题,其中膈肌功能障碍是导致困难撤机或延长撤机的重要原因之一.准确评估并调整膈肌功能状态可提高撤机成功率,减少呼吸机相关肺炎、呼吸机相关肺损伤等并发症,减少困难撤机及延迟撤机现象.     

膈肌疲劳与肌凝蛋白重链

膈肌疲劳在COPD及呼吸衰竭的发生机制中有重要意义。膈肌收缩功能受多种重要收缩蛋白分子的调节。其中 ,肌凝蛋白重链更具有特殊的生理及病理意义。本文对膈肌疲劳的相关因素及各种病理情况下膈肌的微观变化、膈肌疲劳与肌凝蛋白重链的关系以及有关药物对膈肌疲劳的作用等进行了综述。     

氧化乐果急性中毒后对大鼠膈肌功能的影响

急性有机磷农药（ＯＰ）的主要致死原因是呼吸衰竭,当发生呼吸肌麻痹后,阿托品及胆碱酯酶复能剂对其疗效不佳,未获及时诊断和抢救的患者常因呼吸肌麻痹而死亡［１,２］,故已引起临床工作者的高度重视。因此,探讨ＯＰ中毒后呼吸肌麻痹形成的原因,寻求合理有效的防治...     

智能化撤机和经验性撤机的前瞻性随机对照研究

目的 比较智能化撤机和经验性撤机两种撤机方法对机械通气撤机困难患者的疗效.方法 采用前瞻性随机对照研究,按平衡指数最小的原则进行简易的临床试验随机化分组,将62例综合ICU内的撤机困难患者随机分入智能化Smart Care组(SC组,30例)和同步间歇指令通气联合压力支持通气组(SP组,32例)进行撤机试验,两组患者的疾病构成、年龄、性别、入ICU时急性生理慢性健康状况评分(APACHE)Ⅱ以及撤机前机械通气时间差异均无统计学意义.两组患者除撤机方法不同外,其他处理均相同,观察两组的撤机时间、再插管率和机械通气相关并发症的发生率以及ICU滞留率.结果 SC组神经肌肉病变患者、术后呼吸支持患者和呼吸系统疾病患者的撤机时间分别为(49±13)、(67±37)和(25±96)h,明显少于SP组[分别为(223±38)、(106±34)和(502±91)h,X~2值分别为8.33、4.77和4.43,均P<0.05].SC组神经肌肉病变患者、术后呼吸支持患者的ICU滞留时间分别为(9.0 ±1.7)和(7.3±1.9)d,明显低于SP组的(20.8±5.1)和(14.6±1.7)d(X~2值分别为6.74和7.68,均P<0.05).SC组平均调节呼吸机次数为(5±1)次/人明显低于SP组的(13±3)次/人(t=2.73,P<0.05).两组的再插管率、气管切开率、气胸发牛率、呼吸机相关性肺炎(VAP)发生率和皮下气肿发生率比较差异均无统计学意义.结论 CDW智能化撤机法应用于撤机困难患者能够有效地缩短撤机时间,减少ICU滞留时间,并可以减少医生调节呼吸机的负担而节约医疗资源.     

碘缺乏和碘过量对大鼠心肌肌球蛋白重链基因表达的影响

目的观察碘缺乏和碘过量对大鼠心肌肌球蛋白重链(MHC)基因表达的影响。方法Wistar大鼠随机分为低碘(LI)组、适碘(NI)组、5、10、50、100倍高碘(5HI、10HI、50HI、100HI)组,饲养6个月。采用化学发光方法测定血中甲状腺激素(TH)水平,记录大鼠心电图,心脏指数,RT-PCR法检测心肌肌球蛋白重链α和β(α-MHC、β-MHC)mRNA的表达。结果与NI组相比,LI组血清TH水平降低(P<0．01),心脏指数增大(t=2．973,P<0．01),心肌细胞α-MHC mRNA表达量降低(t=4．382,P<0．01),β-MHC mRNA表达量增高(t=5．843,P<0．01)。各HI组血清TH水平较NI组有下降趋势,10H1、50HI、100HI组血清TT3与NI组相比差异有统计学意义(t=4．901、4．838、2．406,P<0．01或0．05),10HI、50HI组血清TT4与NI组相比差异有统计学意义(t=2．162、2．348,P<0．05);但心电图各波段和心脏指数未见明显改变:α-MHC mRNA表达量随摄入含碘量的升高而呈下凋趋势,但与NI组相比差异无统计学意义(P>0．05),而50HI和100HI组β-MHC mRNA表达量显著上调(t=2．632、4．127．P<0．05或0．01)。结论碘缺乏和碘过量均可导致Wistar大鼠甲状腺功能减退(甲减),影响心脏受TH调节的靶基因的表达量,进而影响心脏的功能状态。     

无创通气管路漏气时自动触发对人机交互作用的影响

目的 研究涡轮供气、单管路呼吸机出现自动触发与管路漏气的关系及自动触发对人-机交互作用的影响.方法 对临床中常用的5种涡轮供气、单管路呼吸机,模拟肺和14名志愿者进行研究.以平台型漏气阀建立定量漏气装置,测定不同漏气级别时管路内的呼吸力学曲线.采用SPSS 10.0软件.数据以-x±s表示,组间均数比较采用方差分析.在模拟肺研究中采用logistic回归对自动触发与各变量间的相关性进行分析.结果 以双水平气道正压(BiPAP)模式工作时,在模拟肺研究中不同呼吸机出现自动触发次数占总测试次数百分比达24%～90%,自动触发的出现与漏气量呈正相关(β=0.709,相对危险度(OR)=2.032).在志愿者研究中,随着漏气量的增加,14名志愿者均出现自动触发,同时呼吸频率增快,潮气量减小.结论 在涡轮供气、单管路呼吸机,自动触发随管路漏气量增加而增多.自动触发可能与无创呼吸机在漏气增加时流速基线补偿不足有关.自动触发使受试者的通气效率降低.     

高龄老年呼衰患者有创机械通气时血液动力学的影响

目的探讨高龄呼衰患者机械通气使用对血液动力学的影响。方法54例入选对象均使用有创机械通气纠正呼衰,在病情稳定时监测呼吸力学和无创心功能。设定机械通气VT按12ml/kg、10ml/kg、8ml/kg、6ml/kg,PEEP为0、5、8、10cmH2O,及为PEEPi 75%、100%、125%共28种通气状况时,高龄患者机械通气时血液动力学的变化。结果1.高龄患者在VT达≥10ml/kg时,在PEEP设定为0～10cmH2O范围内;或PEEP≥10cmH2O时,VT设定在6～12ml/kg范围内时,均可产生较高的气道峰压和吸气平台压,产生HR和CVP增高,SBP、DBP、CI和CO下降等血流动力学异常。2.同样,PEEP设定为PEEPi125%时,VT分别为每公斤体重6、8、10、12ml时,SBP、DBP、CO和CI逐渐降低,HR、CVP与VT成正相关。当VT设定为12ml/kg,PEEP为PEEPi的125%时,表现为气道峰压和吸气末平台压明显高,肺顺应性低。并出现SBP、DBP、CO和CI明显下降,HR和CVP增高等血液动力学的改变。3.若PEEP和VT同时增大时,气道峰压和吸气末平台压升高更明显,肺顺应性更低;患者的SBP、DBP、CI、CO下降更明显,HR和CVP增高幅度更大。结论通过本临床研究我们发现高龄呼衰患者有创机械通气时潮气量等于或大于10ml/kg时、PEEP等于或大于10cmH2O或为PEEPi 125%时,易出现血液动力学的影响;     

Eccentric contraction-induced injury to type I, IIa, and IIa/IIx muscle fibers of elderly adults

Muscles of old laboratory rodents experience exaggerated force losses after eccentric contractile activity. We extended this line of inquiry to humans and investigated the influence of fiber myosin heavy chain (MHC) isoform content on the injury process. Skinned muscle fiber segments, prepared from vastus lateralis biopsies of elderly men and women (78 ± 2 years, N = 8), were subjected to a standardized eccentric contraction (strain, 0.25 fiber length; velocity, 0.50 unloaded shortening velocity). Injury was assessed by evaluating pre- and post-eccentric peak Ca²⁺-activated force per fiber cross-sectional area (F _max). Over 90% of the variability in post-eccentric F _max could be explained by a multiple linear regression model consisting of an MHC-independent slope, where injury was directly related to pre-eccentric F _max, and MHC-dependent y-intercepts, where the susceptibility to injury could be described as type IIa/IIx fibers > type IIa fibers > type I fibers. We previously reported that fiber type susceptibility to the same standardized eccentric protocol was type IIa/IIx > type IIa = type I for vastus lateralis fibers of 25-year-old adults (Choi and Widrick, Am J Physiol Cell Physiol 299:C1409–C1417, 2010). Modeling combined data sets revealed significant age by fiber type interactions, with post-eccentric F _max deficits greater for type IIa and type IIa/IIx fibers from elderly vs. young subjects at constant pre-eccentric F _max. We conclude that the resistance of the myofilament lattice to mechanical strain has deteriorated for type IIa and type IIa/IIx, but not for type I, vastus lateralis fibers of elderly adults.     

Human homozygous R403W mutant cardiac myosin presents disproportionate enhancement of mechanical and enzymatic properties

Familial hypertrophic cardiomyopathy (FHC) is associated with mutations in 11 genes encoding sarcomeric proteins. Most families present mutations in MYBPC3 and MYH7 encoding cardiac myosin-binding protein C and beta-myosin heavy chain. The consequences of MYH7 mutations have been extensively studied at the molecular level, but controversial results have been obtained with either reduced or augmented myosin motor function depending on the type or homogeneity of myosin studied. In the present study, we took advantage of the accessibility to an explanted heart to analyze for the first time the properties of human homozygous mutant myosin. The patient exhibited eccentric hypertrophy with severely impaired ejection fraction leading to heart transplantation, and carries a homozygous mutation in MYH7 (R403W) and a heterozygous variant in MYBPC3 (V896M). In situ analysis of the left ventricular tissue showed myocyte disarray and hypertrophy plus interstitial fibrosis. In vitro motility assays showed a small, but significant increase in sliding velocity of fluorescent-labeled actin filaments over human mutant cardiac myosin-coated surface compared to control (+18%; P<0.001). Mutant myosin exhibited a large increase in maximal actin-activated ATPase activity (+114%; P<0.05) and Km for actin (+87%; P<0.05) when compared to control. These data show disproportionate enhancement of mechanical and enzymatic properties of human mutant myosin. This suggests inefficient ATP utilization and reduced mechanical efficiency in the myocardial tissue of the patient, which could play an important role in the development of FHC phenotype.     

苦参碱对去甲肾上腺素促心肌细胞肥大及肌球蛋白重链基因表达的影响

目的 :探讨苦参碱对去甲肾上腺素 (NE)促心肌细胞肥大及肌球蛋白重链 (MHC)基因表达作用的影响。方法 :采用测定心肌细胞直径、数目 ,3 H 亮氨酸 (3 H Leu)掺入率及分子杂交的方法 ,观察NE对大鼠培养心肌细胞肥大及MHC基因表达的影响 ,并用苦参碱治疗。结果 :NE显著促进心肌细胞直径增大 (P <0 .0 5 )及3 H Leu掺入率的增加 (P <0 .0 1) ,并诱导心肌细胞 β MHC基因表达 ,α MHC基因表达相应减少 ,苦参碱对NE促心肌细胞直径增大及3 H Leu掺入率增加作用无明显影响 ,但显著抑制NE致心肌细胞MHC同工蛋白的病理性转换作用 ,即增加α MHC基因表达 ,减少 β MHC基因表达。 结论 :苦参碱对NE促心肌细胞肥大作用无明显影响 ,但显著逆转NE致MHC同工蛋白的病理性转换作用 ,故苦参碱在心肌细胞肥大的防治中仍有一定价值