吸入一氧化氮对胎粪吸入综合征新生猪脑的保护作用

目的探讨机械通气下吸入一氧化氮(NO)对胎粪吸入综合征(MAS)新生猪脑不同部位胆碱能神经元的保护作用及对星形胶质细胞增殖的影响。方法 建立新生猪胎粪吸入模型,并予间歇正压通气,随机分为胎粪吸入组(n=10)和NO治疗组(n=4),另设正常对照组(n=4)。HE染色计数大脑皮质、海马及基底节神经元细胞,免疫组化法检测皮层、海马及基底节胆碱乙酰基转移酶(ChAT)和胶质纤维酸性蛋白(GFAP)免疫阳性细胞数。结果 胎粪吸入组脑不同部位的神经元细胞和ChAT阳性细胞数均较正常对照组减少[神经元细胞:皮质(29.6±2.3)比(58.2±3.8),海马(27.0±12.7)比(56.0±3.7),基底节(25.0±4.6)比(56.0±4.6);ChAT阳性细胞:皮质(16.7±3.9)比(38.3±9.0),海马(17.5±2.7)比(34.3±11.6),基底节(17.0±1.2)比(35.3±7.1),P均<0.01],GFAP阳性细胞数增多[皮质(54.8±11.0)比(22.0±5.5),海马(54.9±14.7)比(21.0±1.7),基底节(53.8±7.1)比(19.0±4.6),P均<0.001)]。NO治疗组神经元细胞数和ChAT阳性细胞数均多于胎粪吸入组,GFAP阳性细胞数少于胎粪吸入组,P均<0.05。结论 新生猪MAS后吸入NO可减少脑不同部位胆碱能神经元的丢失及星形胶质细胞的增殖,提示吸入NO可能对MAS引起的脑损伤具有保护作用。     

神经生长因子对难治性癫癎儿童脑海马癎性放电区神经细胞的影响

目的：探讨神经生长因子（NGF）对难治性癫癎儿童海马癎性放电区星形胶质细胞和神经元的影响。方法：对术中取下的癫癎儿童脑海马癎性放电区组织块,采用解离细胞即刻培养技术,在空白对照组及NGF浓度分别为12.5、50、100 ng/mL 的条件下进行培养,通过免疫荧光细胞化学法,以双苯酰亚胺（Bb）染核,联合细胞特异性标志蛋白GFAP、MAP2分别标记星形胶质细胞、神经元,在倒置荧光显微镜下计数神经细胞总数,并计算相应的阳性细胞比率。结果：NGF 作用 4 h 后,海马区 GFAP 阳性的星型胶质细胞比率及 MAP2 阳性神经元细胞比率较空白对照组升高,并随着 NGF 浓度的增高而增加（P<0.05）。结论：NGF 对癫癎儿童损伤海马区的GFAP+ 星形胶质细胞和MAP2+神经元可能起到一定的保护作用。     

一氧化氮吸入治疗对胎粪吸入综合征患儿氧合功能及气道炎症反应的影响

目的 探讨吸入小剂量一氧化氮(NO)对胎粪吸入综合征(MAS)患儿氧合功能、气道炎症反应的影响.方法 选择河北省儿童医院新生儿科重症监护病房2005年2月至2007年4月收治的55例机械通气的MAS患儿,随机分为A组(机械通气+NO吸入治疗组)和B组(机械通气组),于治疗起始时(0 h)、治疗后24、72 h监测氧合指数(OI)、动脉/肺泡氧分压比值(a/APO2)以及肺动脉压(PAP)的变化.取静脉血和支气管肺泡灌洗液测定细胞因子IL-8、IL-10的含量.结果 A组患儿在吸入NO[(10～20)×10-6]后OI、PAP逐渐下降(P<0.05),a/APO2逐渐上升(P<0.05).A组机械通气时间[(77.38±13.97) h]明显低于B组[(104.27±10.53) h](P<0.05).A组氧暴露时间[(158.70±47.23) h]明显少于B组[(202.15±61.92) h](P<0.05).A组平均住院天数[(13.24±3.62) d]也明显低于B组[(16.81±3.43) d](P<0.05).但是两组间病死率及气漏、肺出血、颅内出血(Ⅱ～Ⅳ级)的发病率间差异无显著性(P>0.05).血清及支气管肺泡灌洗液中IL-8水平于应用NO后24 h逐渐下降,IL-10水平逐渐增高,两者应用NO后差异均有显著性(P<0.05).结论 吸入NO作为治疗重症MAS的一种特殊疗法,具有降低PAP、改善氧合状态、缩短通气时间的作用.吸入NO可能在整体上调节MAS所致的肺部炎症反应,对机体有保护作用.     

胎粪吸入综合征患儿支气管肺泡灌洗液及血一氧化氮和内皮素水平的变化

目的了解胎粪吸入综合征(MAS)患儿支气管肺泡灌洗液(BALF)及血中一氧化氮(NO)和内皮素(ET1)浓度的变化,探讨MAS患儿肺部损害的发病机制。方法MAS患儿60例随机分为A、B两组。A组29例,为Ⅱ型呼衰需呼吸机辅助呼吸者;B组31例,为轻度胎粪吸入性肺炎患儿;C组32例,为健康新生儿对照组。3组均于生后1、3、5、10d取静脉血,A组于生后1、3d、撤机前取BALF。NO测定应用硝酸盐还原法,ET1应用放射免疫法。结果MAS患儿初期血中NO浓度降低,ET1浓度升高,随着病程进展重度MAS患儿出现NO的异常增高,而ET1降至正常以下。BALF中NO浓度随病程进展逐渐升高,ET1浓度逐渐降低。结论NO降低、ET1升高可能参与MAS早期肺部病理生理变化,导致肺血管过度收缩使肺动脉压力升高,而后期内源性NO产生异常增加,可能参与重度MAS患儿后期的持续的肺部炎症反应及肺损害。     

比例辅助通气对重症胎粪吸入幼兔肺组织肿瘤坏死因子-α和白细胞介素-8水平的影响

目的探讨比例辅助通气(PAV)对胎粪吸入幼兔肺组织中肿瘤坏死因子-α(TNF-α)和白细胞介素-8(IL-8)水平的影响。方法将30只日龄20～30天的幼兔随机分为灌入胎粪后实施PAV组和灌入胎粪后实施同步间歇指令通气(SIMV)组,并与胎粪吸入不予通气组(MAS组)及灌生理盐水组(对照组)进行比较,各组分别于8h后处死,ELISA法检测肺组织匀浆及肺泡灌洗液中TNF-α、IL-8的含量。结果 (1)肺组织湿干比PAV组(7.81±0.52)、SIMV组(8.79±0.96)、MAS组(7.12±0.74)均高于对照组(4.22±0.30),SIMV组高于PAV组和MAS组,差异有统计学意义(P均<0.05);PAV组与MAS组差异无统计学意义(P>0.05)。(2)PAV组、SIMV组和MAS组肺组织匀浆TNF-α含量(pg/ml)[(872.6±104.0)、(973.9±114.5)和(707.1±39.1)]及IL-8含量(pg/ml)[(787.0±89.3)、(872.9±87.0)和(641.4±60.3)]均高于对照组[(401.1±74.5)和(381.3±63.3)],SIMV组高于PAV组和MAS组,PAV组高于MAS组,差异有统计学意义(P均<0.05)。(3)PAV组、SIMV组及MAS组肺泡灌洗液TNF-a含量[(644.4±89.3)、(787.1±100.6)和(536.0±28.5)]均高于对照组(301.8±75.9),SIMV组高于PAV组,差异有统计学意义(P均<0.05);PAV组、SIMV组及MAS组IL-8含量[(653.0±93.3)、(744.7±81.8)和(532.4±60.1)]均高于对照组(280.9±70.8),SIMV组高于PAV组和MAS组,PAV组高于MAS组,差异有统计学意义(P均<0.05)。结论胎粪在炎症反应中可促进TNF-α、IL-8释放,PAV治疗MAS时所致肺损伤程度较SIMV小。     

胎粪吸入综合征并发持续肺动脉高压时血中内皮素-1和一氧化氮水平及其意义

为探讨胎粪吸入综合征并发持续肺动脉高压时血清内皮素-1(ET-1)和一氧化氮(NO)水平变化,采用硝酸还原法和放射免疫法分别测定15例对照组、11例胎粪吸入综合征(MAS)组和9例MAS并发持续肺动脉高压(PPHN)组3组新生儿血中NO和ET-1的水平。结果:对照组、MAS和MAS并发PPHN组NO水平分别为(58.0±13.5)μmol/L、(40.6±7.3)μmol/L和(20.5±4.8)μmol/L;EI-1水平分别为(21.8±5.2)ng/L、(30±6.5)ng/L和(60.2±8.6)ng/L。MAS与对照组比较差异无显著性,MAS并发PPHN组与对照组和MAS组比较差异有显著性(P<0.01和P<0.05)。NO和ET-1与肺动脉压力有明显负相关和正相关(r=-0.653、0.726,P<0.01)。提示MAS并发PPHN时血中ET-1升高,NO降低,两者与肺动脉压力有明显的相关性,ET-1、NO水平改变与MAS并发PPHN发生机制有关。     

吸入一氧化氮治疗早产儿低氧性呼吸衰竭的临床研究

目的探讨吸入一氧化氮（iNO）治疗早产儿低氧性呼吸衰竭的疗效及安全性。方法将2007年3月至2010年3月本院收治的因呼吸窘迫综合征引起低氧性呼吸衰竭,且胎龄〈34周的早产儿随机分为干预组（iNO组）和对照组。两组均采用基础治疗及机械通气等常规治疗。iNO组在常规治疗基础上加用NO吸入治疗,NO吸入浓度从5ppm开始,最高20ppm,持续吸入时间24～72h,同时动态监测主要血气指标,包括pH、PaO2、PaCO2、PaO2/FiO2、SaO2、动脉-肺泡血氧分压差[（A-a）PO2]以及氧合指数（OI）的变化。结果 iNO组（n=16）与对照组（n=19）比较,治疗后12、24、48h及72h血气指标明显改善（P均〈0.05）,其中24h最明显[pH（7.4±0.1）比（7.2±0.1）,PaO2（68.7±10.1）mmHg比（51.6±11.3）mmHg,PaCO2（38.6±8.2）mmHg比（48.4±12.1）mmHg,PaO2/FiO2（206.8±32.5）mmHg比（165.2±22.7）mmHg,SaO2（0.93±0.07）比（0.81±0.09）,（A-a）PO2（227.4±126.8）mmHg比（346.7±160.2）mmHg,OI（5.8±3.5）比（9.2±6.2）]。iNO组气道NO2浓度〈1ppm,出血时间正常,死亡数及并发症的发生未增加。结论 iNO治疗早产儿低氧性呼吸衰竭能够显著改善氧合功能,纠正高碳酸血症和酸中毒,并未增加不良反应的发生。     

吸入低浓度一氧化氮对胎粪吸入综合征患儿机体抗氧化能力的影响

目的 探讨吸入低浓度一氧化氮(iNO)对胎粪吸入综合征(MAS)患儿机体氧化-抗氧化平衡的影响.方法 将我院新生儿科病房的55例MAS患儿随机分为机械通气+iNO组(A组,n=25)、机械通气组(B组,n=30),并选择我院同期的健康足月新生儿为对照组(C组,n=30).iNO前A、B组均接受气管插管、气管内吸痰、机械通气及静脉滴注抗生素等一般治疗.A组于入院后1～2 h给予iNO治疗,分别在0、24、72 h监测各组患儿静脉血血清中超氧化物歧化酶(SOD)、丙二醛(MDA)、总抗氧化能力(T-AOC)水平.结果 三组患儿一般情况比较差异无显著性.随着NO吸入.A组SOD、T-AOC渐增高,MDA含量降低(P＜0.05).B组SOD在24 h降低,而在72 h呈增高改变,MDA含量变化与之相反,T-AOC呈渐增高改变(P＜0.05).A组机械通气时间及氧暴露时间分别为(77.38±13.97)h与(158.70±47.23)h,明显低于B组[(104.27±10.53)h与(202.15±61.92)h],差异有显著性(P＜0.05),但两组患儿病死率及气漏、肺出血、颅内出血(Ⅱ～Ⅳ级)的发生率差异无显著性(P＞0.05).结论 iNO可减少机械通气及氧暴露时间.MAS患儿体内存在不同程度的氧化-抗氧化失衡,iNO多显示抗氧化活性,有助于机体氧化-抗氧化平衡的调节,对机体具有保护性作用.     

碱性成纤维细胞生长因子对新生鼠缺氧缺血性脑损伤胶质纤维酸性蛋白表达的影响

目的探讨外源性碱性成纤维细胞生长因子（bFGF）对新生大鼠缺氧缺血性脑损伤（HIBD）后海马胶质纤维酸性蛋白（GFAP）表达的影响。方法通过结扎并剪断7日龄新生Wistar大鼠右侧颈总动脉，吸入8％氧气和92％氮气2h制备新生鼠HIBD模型，设假手术组、生理盐水对照组、bFGF治疗组。通过免疫组织化学方法和计算机图像分析技术检测3组大鼠不同时点（术后d4、7、10、17、24）海马CAI区GFAP表达强度变化。结果假手术组海马内GFAP阳性细胞数量和染色强度术后d7达高峰：对照组、治疗组GFAP表达较假手术组增多，治疗组增多更明显，术后d10达高峰，GFAP阳性细胞主要分布于海马CAI、CA3区．术后d4、10、17组比较差异有显著性（P均〈0．05）。结论1．新生鼠HIBD后脑缺血易损伤区GFAP表达增加，可能与脑损伤后神经细胞再生有关；2．外源性给予bFGF可增强新生鼠脑缺氧缺血后中枢神经系统GFAP表达，在神经细胞损伤的修复中发挥一定保护作用。     

不同日龄大鼠海马神经发生的研究

目的 探讨年龄因素对大鼠海马齿状回神经发生的影响及新生神经细胞的分化.方法选择7、14、28、60、180 d 5个日龄组SD大鼠,每组8只,雌雄不限.采用5-溴脱氧尿核苷(BrdU)标记新生细胞,以β微管蛋白(TuJ1)、胶质纤维酸性蛋白(GFAP)双标免疫组织化学方法分别标记其神经元和胶质细胞,检测不同日龄大鼠海马齿状回神经发生,了解新生细胞向神经元细胞和神经胶质细胞分化比例.结果5个日龄组大鼠均有海马齿状回颗粒细胞层神经发生现象,细胞形态多样,呈圆形、椭圆形、菱形等,胞核较大,分布于整个颗粒细胞层.日龄7、14、28、60、180 d组大鼠BrdU阳性细胞数分别为158.07±5.37、141.28±7.27、116.93±9.24、76.56±6.88、41.42±4.45,随着日龄的增长,大鼠海马齿状回新生细胞数量渐减少(P＜0.05);日龄7、14、28、60、180 d组大鼠BrdU阳性细胞同时表达TuJ1的比例分别为81.6.%、78.9%、83.9%、80.2%、82.4%,组间比较无明显差异(P＞0.05);各组新生细胞中4%～5%为GFAP阳性.还有少数齿状回的BrdU阳性细胞并不同时表达TuJ1或GFAP.结论在生理状态下不同日龄大鼠海马齿状回存在神经细胞增殖现象,而且随着日龄增加,神经元再生的能力渐减弱,新生细胞多分化为神经元细胞.     

Newborn piglets with meconium aspiration resuscitated with room air or 100% oxygen

We investigated whether newborn piglets exposed to hypoxemia and severe meconium aspiration could be reoxygenated with room air as efficiently as with 100% O(2). Twenty-one 2- to 5-d-old piglets were randomly divided into three groups: 1) the room air group: hypoxemia, meconium aspiration, and reoxygenation with room air (n = 8); 2) the O(2) group: hypoxemia, meconium aspiration, and reoxygenation with 100% O(2) (n = 8); and 3) the control group: meconium aspiration, and reoxygenation with room air (n = 5). Hypoxemia was induced by ventilation with 8% O(2) until the mean blood pressure reached <20 mm Hg or the base excess reached <-20 mM. At this point, reoxygenation was started with either room air or 100% O(2). Three milliliters per kilogram of meconium 110 mg/mL was instilled into the trachea immediately before the start of reoxygenation. The O(2) tension in arterial blood was significantly lower in the room air group; at 5 min of reoxygenation it was 9.1 +/- 0.5 kPa versus 43.5 +/- 6 kPa in the O(2) group (p < 0.05). At 5 min of reoxygenation the tidal volume per kilogram was 12.1 +/- 0.7 mL/kg in the room air group and 13.1 +/- 0.9 mL/kg in the O(2) group (NS). There were no significant differences between the room air and the O(2) groups during 120 min of reoxygenation in mean arterial blood pressure, pulmonary arterial pressure, cardiac index, base excess, or plasma hypoxanthine. In conclusion, hypoxic newborn piglets with meconium aspiration were found to be reoxygenated as efficiently with room air as with 100% O(2).     

Comparison of pulmonary and inflammatory effects of lipid- and water-soluble components in meconium in newborn piglets

To understand the pathogenesis of meconium aspiration syndrome, we compared the pulmonary and inflammatory effects of the water and lipid extracts of human meconium instilled into the lungs of newborn piglets. The piglets were artificially ventilated, made hypoxemic, and randomized into three groups. At start of reoxygenation, 3 ml/kg of one of the following mixtures was instilled intratracheally: (1) meconium (n = 12); (2) water extract of meconium (n = 12), and (3) lipid extract of meconium (n = 12). During 8 h of reoxygenation, hemodynamics, pulmonary gas exchange, lung mechanics, and interleukin-8 concentrations in tracheobronchial aspirates were monitored. Oxygenation index (p = 0.04) and mean airway pressure (p = 0.04) increased more in the lipid extract group than in the water extract group. Dynamic compliance and mean arterial blood pressure decreased (p < 0.05) in the meconium and lipid extract groups, but not in the water extract group. At 8 h of reoxygenation, the interleukin-8 concentration in the tracheobronchial aspirates was three times higher in the lipid extract group as compared with the water extract group (110 +/- 102 vs. 37 +/- 27 pg/ml; p = 0.02). In conclusion, pulmonary dysfunction in meconium aspiration syndrome is caused by both the water- and lipid-soluble fractions of meconium, with stronger inflammatory and more detrimental effects promoted by the lipid extract than the water extract.     

Nitric oxide inhalation inhibits pulmonary apoptosis but not inflammatory injury in porcine meconium aspiration

To investigate the possible protective effects of nitric oxide (NO) inhalation in newborns with meconium aspiration, 18 10-12-d-old piglets were studied for 6h after an intratracheal bolus (3 ml/kg) of a 65-mg/ml mixture of human meconium. Twelve of the piglets were treated with continuous NO inhalation at a dose of 1 ppm ( n = 6) or 10 ppm ( n = 6), started 30 min before the insult. Pulmonary haemodynamics and systemic oxygenation were followed, and lung tissue samples were studied for signs of inflammation, evidence of ultrastructural injury and apoptotic cell changes. Inhalation of 10 ppm NO, in contrast to 1 ppm NO, significantly delayed the meconium-induced pulmonary pressure rise and the increase in intrapulmonary shunt fraction, and maintained better oxygenation in the piglets. Histologically and biochemically, treatment with 1 or 10 ppm NO inhalation did not protect the lungs against meconium-induced inflammatory injury. Further, ultrastructural lung tissue analysis revealed a significant amount of alveolar exudate and oedematous alveolar epithelium and endothelium after meconium instillation, also in the lungs treated with NO inhalation. However, the increase in apoptotic epithelial cell deaths, previously shown to be stimulated by intratracheal meconium, was significantly impeded after inhalation of 10 ppm. These results thus show that early continuous NO inhalation controls the rise in pulmonary artery pressure and improves the efficiency of arterial oxygenation, and further prevents the increase in epithelial apoptosis, but does not protect against early inflammatory damage caused by meconium aspiration.     

Albumin mixed with meconium attenuates pulmonary dysfunction in a newborn piglet model with meconium aspiration

We hypothesized that lipids and bile acids in meconium may induce pulmonary insufficiency in newborns. Because albumin may bind these components we studied the effect of albumin on meconium-induced lung injury in piglets. We measured concentration of FFA in the meconium (110 mg dry weight/mL) and added albumin to provide a molar FFA to albumin ratio of 1:1. Newborn piglets, 0-2 d of age, artificially ventilated and exposed to hypoxemia by ventilation with 8% O2, were randomized to group A receiving meconium (n = 12) or group B receiving meconium + albumin (n = 12), 3 mL/kg intratracheally. The animals were reoxygenated for 8 h. Reoxygenation was started when mean blood pressure was <20 mm Hg or base excess was <-20 mM. Pulmonary function was assessed in parallel with pulmonary hemodynamics. From the start of reoxygenation and the next 8 h we found a significant difference (by ANOVA) between the two groups in oxygenation index (p = 0.005), with an increase from 1.6 +/- 0.2 to 6.1 +/- 6.8 (p = 0.04) in the meconium group and from 1.8 +/- 0.3 to 3.1 +/- 3.1 (NS) in meconium + albumin group. There were also significant differences (by ANOVA) between the groups in favor of the treatment group concerning need of inspired fraction of O2, mean airway pressure, dynamic compliance of the respiratory system, time constant, ventilation index, and pulmonary vascular resistance. In conclusion, albumin given concurrently with meconium significantly reduced detrimental effects of meconium aspiration in the lungs of newborn piglets.     

Inhaled nitric oxide treatment inhibits neuronal injury after meconium aspiration in piglets

Background

Meconium aspiration-induced hypertensive lung injury is frequently associated with neuronal damage. Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension, but its effects on the brain are poorly known.

Aims

The aim of this study was to determine the effects of iNO treatment on the neuronal tissue after meconium aspiration.

Study design

71 anesthetized, catheterized and ventilated newborn piglets were studied for 6 h. Thirty-five piglets were instilled with a bolus of human meconium intratracheally and 36 piglets with saline instillation served as controls. Nineteen meconium piglets and 17 control piglets were continuously treated with 20 ppm of iNO, started at 30 min after the insult. The extent of neuronal injury was analysed histologically, and the levels of brain tissue lipid peroxidation products, reduced glutathione (GSH), myeloperoxidase activity and oxidized DNA were analysed as indicators of oxidative stress.

Results

iNO treatment diminished the pulmonary hypertensive response caused by meconium aspiration, but did not change systemic or carotid hemodynamics. NO administration was associated with reduced neuronal injury and diminished amount of oxidized DNA in the hippocampus of the meconium piglets. Further, iNO treatment was associated with decreased level of GSH in the cortex, but no change in lipid peroxidation production or myeloperoxidase activity was detected in any of the studied brain areas.

Conclusions

Our results suggest that iNO treatment may inhibit DNA oxidation and neuronal injury in the hippocampus, associated with newborn meconium aspiration.     

Meconium induced IL-8 production and intratracheal albumin alleviated lung injury in newborn pigs

We have recently shown that albumin added to meconium before intratracheal instillation in newborn pigs limits detrimental effect on the lungs and reduces increase of IL-8. The aim of this study was to test the effect of albumin instillation as rescue treatment in meconium aspiration syndrome (MAS). MAS was induced in hypoxic piglets by lung instillation of meconium (MAS I = 675 mg/kg, n=12; MAS II=540 mg/kg, n=14). Morbidity and mortality differed (MAS I, dead=7/12; MAS II, dead=5/14). MAS groups were randomized to postmeconium instillation of either bovine albumin (30%, 1.4 mL/kg; MAS I, n=6; MAS II, n=7) or isotonic saline (9 mg/mL, 1.4 mL/kg; MAS I, n=6; MAS II, n=7). The controls (n=4) were tested by sequential instillation of saline (9 mg/mL, 5 mL/kg) and albumin (30%, 1.4 mL/kg). Lung function and gas exchange deteriorated significantly after instillation of meconium [oxygenation index (OI): MAS I, +814%; MAS II, +386%; ventilation index (VI): MAS I, +256%; MAS II, +162%; compliance: MAS I, -53%; MAS II, -44%]. Increases of tracheal IL-8 correlated to deterioration of lung function were 10- (MAS I) and 5-fold (MAS II) (p <0.001). Lung compliance was higher in albumin instillation versus saline instillation (MAS I, p=0.008; MAS II, p=0.002). Albumin did not influence intergroup differences in IL-8, hemodynamics, OI, or VI. MAS-induced IL-8 increases correlated with deterioration of lung function (OI, VI, and compliance). Rescue treatment with albumin in meconium aspiration improved lung compliance in piglets and may represent a new therapeutic approach to MAS.     

Dexamethasone treatment attenuates pulmonary injury in piglet meconium aspiration

To investigate the pulmonary effects of steroid treatment in neonates with meconium aspiration, 25 10- to 12-d-old piglets were studied for 6 h after an intratracheal bolus of human meconium. Dexamethasone (0.5 mg/kg) was given in two treatment schedules, either 1 h before (n = 6) or 1 h after meconium instillation (n = 8). Eight piglets served as controls. Three additional piglets were given dexamethasone without meconium instillation. Pulmonary hemodynamics and oxygenation were followed, and lung tissue samples investigated for signs of inflammation and ultrastructural injury, including apoptosis. Pulmonary artery pressure and vascular resistance increased after meconium instillation, but this rise was significantly prevented after prophylactic dexamethasone. This treatment also improved the acutely deteriorated oxygenation of the piglets after meconium insufflation. Prophylactic, but not early, dexamethasone treatment further protected the lungs from the ultrastructural changes caused by meconium instillation. Additionally, the increase of apoptotic epithelial cell deaths was significantly prevented by both dexamethasone treatments. These results show that prophylactic dexamethasone treatment significantly attenuates the early pulmonary hemodynamic deterioration and structural lung damage caused by meconium aspiration. Further studies on the apoptosis-inhibiting effect of dexamethasone administration in neonatal lungs exposed to heavy meconium are warranted.     

Pulmonary function in children after neonatal meconium aspiration syndrome]

BACKGROUND: Meconium aspiration syndrome is a disease of the newborn mature or post mature. The acute pulmonary consequences can be extremely severe. In the few studies of the long-term pulmonary sequelae, it seems that certain children surviving meconium aspiration syndrome keep an obstructive syndrome. The aim of our study was to assess long term respiratory residual damage from meconium aspiration syndrome. METHODS: During a seven-year period going from 1994 to 2000, we reviewed the files of children hospitalized in neonatology department of Sfax for meconium aspiration syndrome. The children who were convoked (group M: n=27), underwent spirometry, followed by an exercise stress. An age matched control group (group C: n=23) of healthy children was investigated in the same way. RESULTS: The group M comprised 15 boys and 12 girls aged four to 11, an average of 7+/-1.9 years. With the study of the respiratory function, we did not find an obstructive syndrome. Spirometry revealed a total pulmonary capacity in an average of 133+/-55.65% of theoretical (group M) versus 105.5+/-27.96% of theoretical (group C) (P<0,01), testifying to alveolar hyperinflation. Spirometry fulfilled 5, 10 and 15 min after exercise showed a FEV1 reduction of respectively 8.5 versus 2 (P<0.05); 9.5 versus 3 (P<0.01) and 10.5 versus 4 (P<0.05). CONCLUSION: Children surviving meconium aspiration syndrome tend to develop alveolar hyperinflation and airway hyperreactivity to exercise.     

Meconium aspiration induces neuronal injury in piglets

Aim: Meconium aspiration-induced hypertensive lung injury, especially when connected with perinatal asphyxia, has been associated with brain damage. We aimed to determine the neuronal injury induced by pulmonary meconium contamination alone and with concurrent asphyxia. Methods: 36 anaesthetized and ventilated newborn piglets were haemodynamically monitored for 6 h. Seven piglets without concurrent asphyxia and seven piglets with asphyxia were instilled with a bolus of human meconium intratracheally. Seven piglets had only asphyxia and 15 piglets served as controls. The brains were studied histologically. Results: Meconium aspiration did not change systemic haemodynamics acutely, while its combination with asphyxia diminished the abrupt postasphyxic systemic hypertensive peak and resulted in a transient increase in carotid artery flow, not seen after isolated asphyxia. Systemic pressure declined after 4 h in all insulted groups, but only isolated asphyxia was associated with a sustained decrease in carotid artery flow. Arterial oxygenation remained normal, except during the acute insults. Brain examination after meconium instillation indicated neuronal injury, especially in the CA3 region of the hippocampus. Asphyxia resulted in neuronal injury in the cortical, cerebellar and hippocampal hilus regions.
Conclusion: Severe meconium aspiration itself may result in hippocampal neuronal injury.     

Asphyxia aggravates systemic hypotension but not pulmonary hypertension in piglets with meconium aspiration

Meconium aspiration and birth asphyxia are both separately connected to significant pulmonary and systemic hemodynamic changes in newborns, but, although these insults frequently coexist, their combined effects on the neonatal circulation are still controversial. To determine the pulmonary and systemic circulatory changes induced by pulmonary meconium contamination with concurrent asphyxia, 41 anesthetized and ventilated newborn piglets (10-12 d) were studied for 6 h. Eleven piglets were instilled with a bolus of human meconium intratracheally, and 10 piglets had meconium instillation with immediate induction of an asphyxic insult. Eight piglets had only asphyxia and 12 ventilated piglets served as controls. Meconium instillation (with and without asphyxia) resulted in a sustained decrease in the oxygenation, which remained, however, on the control level in the asphyxic group. Although meconium insufflation (with and without asphyxia) increased pulmonary artery pressure and vascular resistance progressively during the study period, the meconium-induced hypertensive effect was actually diminished by additional asphyxia. Asphyxia alone did not have any effect on these pulmonary hemodynamic parameters. On the other hand, whereas systemic arterial pressure and vascular resistance remained on the control level after meconium instillation alone, asphyxia (with and without pulmonary meconium insult) resulted in a sustained fall in systemic pressure already by 4 h. Our data thus indicate that although the coexisting asphyxia seems to moderate the meconium aspiration-induced pulmonary hypertensive response, this additional asphyxic insult does not affect the associated hypoxemia, but rather significantly exacerbates systemic hypotension.