自体肺体外循环与常规体外循环对细胞因子影响的实验对比研究

目的:探讨以自体肺取代人工肺的体外循环方法对犬体外循环相关性炎症反应的影响。方法:将12只杂种犬随机分为对照组及实验组(每组6只)。对照组在体外循环(CPB)期间使用膜式氧合器,实验组在CPB期间使用自体肺进行氧合,两组均阻断主动脉90分钟、辅助循环30分钟,于CPB前(T1)、转流后60分钟(T2)、停机后60分钟(T3)、停机后120分钟(T4)抽取动脉血,测定血浆肿瘤坏死因子α(TNFα-)、白细胞介素6(IL-6)、白细胞介素8(IL-8)和白细胞介素10(IL-10)浓度。结果:两组实验犬血浆TNFα-、IL-6、IL-8和IL-10的浓度,在T2~T4各时点与体外循环前比较均明显增加(P0.01);T2~T4时点实验组血浆TNFα-、IL-6和IL-8浓度明显低于对照组(P0.01),IL-10浓度明显高于对照组(P0.05)。结论:自体肺体外循环可抑制体外循环过程中促炎细胞因子TNFα-、IL-6和IL-8的释放,促进抗炎细胞因子IL-10的释放,从而减轻常规体外循环引起的全身炎症反应。     

小儿法洛四联症根治术后影响机械通气时间多因素分析

目的:研究小儿法洛四联症(tetralogy of Fallot,TOF)一期根治术后影响呼吸机辅助呼吸时间的因素,以更好地掌握拔管时机,提高外科治疗效果.方法:分析2009年1月至2009年12月期间行TOF一期根治手术的患儿130例.用多元逐步logistic回归分析法,分析性别、年龄、体质量、合并其他畸形、McGoon值、室缺大小、主动脉骑跨程度、右室流出道是否跨瓣增宽、体外循环时间、主动脉阻断时间、左心室舒张末期容积指数等指标对呼吸机辅助呼吸时间的影响.结果:130例患儿呼吸机辅助呼吸时间为5～192(47.59±9.42)h.多元逐步logistic回归分析显示McGoon值和体外循环时间是机械通气使用时间的影响因素.结论:McGoon值<1.5,体外循环时间>100 min是延长机械通气时间的影响因素.     

不同肺保护性通气策略对肺切除术术中通气和术后肺部并发症的影响

目的:评估小潮气量联合不同水平呼气末正压(positive end-expiratory pressure,PEEP)对胸腔镜下肺切除术患者通气氧合和术后肺部并发症(postoperative pulmonary complications,PPCs)的影响.方法:选取空军军医大学唐都医院2019年12月至2020年12月择期行胸腔镜下肺切除患者100例,采用随机数字表法分为两组:低水平PEEP组(LP组)和高水平PEEP组(HP组);LP组于单肺通气(one lung ventilation,OLV)时设置潮气量(tidal volume,VT)6 mL/kg,PEEP≤5 cmH2O,HP组于相同时间点设置VT 6 mL/kg,PEEP 6～10 cmH2O.分别于OLV前(T1)、OLV 60 min(T2)、手术结束(T3)采取桡动脉血液行血气分析;记录T1、T2、T3的心率(heart rate,HR)、脉搏血氧饱和度(pulse oxygen saturation,SpO2)、收缩压/舒张压(systolic blood pressure/diastolic blood pressure,SBP/DBP)、呼气末二氧化碳分压(partial pressure of end-expiratory carbon dioxide,PETCO2)、VT、吸气峰压(peak pressure,Ppeak)、平台压(plateau pressure,Pplat);记录术后7 d内PPCs、胸腔引流管拔除时间、术后3 d内胸腔引流管引流量及术后住院时间.结果:与T1时比较,T2、T3时两组患者HR无明显变化;T2时平均动脉压(mean arterial pressure,MAP)明显降低(P<0.05);两组Ppeak、Pplat明显升高,动态肺顺应性(dynamic compliance,Cdyn)明显降低(P<0.05);两组患者氧合指数(oxygenation index,OI)明显降低,肺泡气-动脉血氧分压差(alveolar gas-arterial oxygen partial pressure difference,A-aDO2)明显升高;T2时两组呼吸指数(respiratory index,RI)明显升高,T3时LP组RI明显升高(P<0.05).与LP组比较,T2时HP组Ppeak明显升高;T2、T3时,HP组Pplat明显升高,驱动压(driving pressure,DP)明显降低,Cdyn明显增高(P<0.05);T2、T3时HP组OI明显升高,A-aDO2、RI明显降低(P<0.05).两组术后7 d PPCs及住院时间差异无统计学意义.结论:小潮气量6 mL/kg联合较高水平PEEP 6～10 cmH2O可改善胸腔镜下肺切除术患者OLV时通气氧合情况,利于术中麻醉管理.     

呼吸机相关性肺损伤的炎症反应机制

机械通气是治疗急性呼吸窘迫综合征的主要手段，但呼吸机应用不当也可能加重原有的肺损伤，引起呼吸机相关性肺损伤。呼吸机相关性肺损伤本质上是生物伤，异常的机械力作用于细胞，激活细胞内信号转导通路，活化炎性细胞，产生大量炎症介质，加重炎症反应。探讨呼吸机相关性肺损伤的炎症反应机制，阻断机械力作用向细胞内的传导和细胞内信号转导途径的激活，减少炎症细胞的激活和炎症介质基因的表达，对于预防呼吸机相关性肺损伤发挥重要作用。     

机械通气救治呼吸衰竭患者的护理

目的 总结慢性阻塞性肺疾病（COPD）并发呼吸衰竭患者应用机械通气治疗的护理经验，方法 对35例入住我院RICU、应用机械通气治疗的COPD合并呼吸衰竭患者的护理方法进行回顾性分析，结果 31例患者经机械通气治疗后，症状明显改善．呼吸衰竭治愈或好转出院，4例患者经抢救无效或家属放弃治疗死亡。结论 严密监测病情、加强呼吸道护理是患者康复的关键；严格执行操作规程、做好基础护理是预防感染、促进康复的重要手段；心理护理是患者保持积极心态，顺利康复的前提。     

体外循环心脏手术后肺损伤的防治策略

近年来随着心脏外科手术技术、体外循环（cardiopulmonary bypass,CPB）和术后监护技术的发展,心脏手术相关并发症的发生率和死亡率均明显降低。但肺功能损伤仍是体外循环心脏手术后常见的并发症之一,绝大多数患者术后均表现出不同程度的肺功能损伤,轻者表现为发热、咳嗽,重者则需要长时间的机械辅助呼吸,     

创伤性全身炎症反应综合征大鼠动物模型的建立

目的　探讨建立可重复的大鼠创伤性全身炎症反应综合征实验模型。 方法　Wistar大鼠30 只大鼠随机分为对照组（A组）,脂多糖组（B组）和实验组（C组）。B组在完成股动脉、股静脉插管后注入脂多糖（LPS,12 mg/kg）,C组采取手术切除1/3肝脏及锤击右侧股骨3次的方法,而A组在同等条件下不进行有创实验。2 h后采血测定血清中丙氨酸氨基转移酶(ALT) 、天冬氨酸氨基转移酶(AST) 、尿素氮(UN) 和肌酐(Cr) 的含量,12 h 后处死大鼠, 取大鼠肺及肝脏组织做病理切片并HE染色。 结果　B组及C组大鼠在建模后血清AL T、AST、UN 和Cr 含量明显增高,与A组比较差异有统计学意义( P<0.01);C组大鼠血清UN ,Cr 含量较B组增高,差异有统计学意义( P<0.05)。光镜观察发现B组及C组大鼠的肝脏和肺脏有组织损伤及明显的炎性反应;B组及C组其肝脏及肺的病理变化差别不明显。 结论　此方法可较方便的制作大鼠创伤性全身炎症反应综合征动物模型。     

炎症反应对急性冠脉综合征患者血小板活性及预后的影响

目的:观察急性冠脉综合征(ACS)患者炎症反应与血小板活性的关系及对预后的影响。方法:348例ACS患者根据是否合并全身炎症反应综合征(SIRS)分为SIRS组(n=128)及对照组(n=220)。两组均给予标准的冠心病二级预防及冠状动脉介入(PCI)治疗。比较两组患者术前血小板最大聚集率(mPAR)、超敏C反应蛋白(hs-CRP)、血清可溶性CD40L(sCD40L)、血清基质金属蛋白酶-9(MMP-9)等指标的差异,分析两组各种炎症因子水平与mPAR的相关性,并比较术后30天两组不良事件的发生率。结果:SIRS组患者mPAR、hs-CRP、sCD40L、MMP-9均明显高于对照组(P均<0.01);两组hs-CRP、sCD40L、MMP-9水平与mPAR之间均呈正相关(P<0.01)。术后30天,SIRS组患者不良事件发生率高于对照组(P<0.01)。结论:炎症反应可能是导致血小板活化的原因之一,合并SIRS的ACS患者预后较差。     

体外循环肺部炎症反应的研究

目的：探讨体外循环过程中应用丝裂原激活蛋白激酶的特异性阻滞剂后观察肺组织损伤程度的变化及对术后肺功能的影响。方法：将18只乳猪随机分为3组，每组6只。实验组（Ⅱ组）体外循环术中用P38丝裂原激活蛋白激酶（p38MAPK）的特异性阻滞剂（SB203580）行肺灌注；Ⅰ组、Ⅲ组为对照组。分别在不同时段取三组动物的肺脏标本，以免疫印迹方法测量肺组织p38MAPK活性。组织学观察肺损伤改变，测量肺组织干湿重比，术后采集动脉血行血气分析，估测肺换气功能。结果：Ⅰ组p38MAPK活性明显增高，Ⅰ组肺损伤与Ⅱ、Ⅲ组相比明显加重。肺换气功能Ⅱ组好于Ⅰ组。结论：体外循环过程中，应用p38MAPK特异性阻断剂有抑制肺损伤的作用，改善术后肺功能。     

机械通气救治呼吸衰竭患者的护理

目的总结慢性阻塞性肺疾病(COPD)并发呼吸衰竭患者应用机械通气治疗的护理经验.方法对35例入住我院RICU、应用机械通气治疗的COPD合并呼吸衰竭患者的护理方法进行回顾性分析.结果 31例患者经机械通气治疗后,症状明显改善,呼吸衰竭治愈或好转出院,4例患者经抢救无效或家属放弃治疗死亡.结论严密监测病情、加强呼吸道护理是患者康复的关键;严格执行操作规程、做好基础护理是预防感染、促进康复的重要手段;心理护理是患者保持积极心态,顺利康复的前提.     

Suppressive effect of phosphodiesterase type 4 inhibition on systemic inflammatory responses after cardiopulmonary bypass

Cardiopulmonary bypass (CPB) induces excessive production of endogenous proinflammatory mediators such as cytokines and elastase, which are responsible for the subsequent development of systemic inflammatory response syndrome (SIRS). In this study, we investigated the protective effect of rolipram against SIRS after CPB. Rats were divided into three groups (n = 5 in each): control (C), rolipram (R), and sham (S). Rats in groups C and R underwent CPB for 60 min followed by 60 min of observation, while those in group S were observed for 120 min without CPB. In group R, 40 μg/kg/min of rolipram was intravenously administered throughout the experiment. CD11b expression on neutrophils was analyzed using flow cytometry. Serum concentrations of tissue necrosis factor α (TNF-α), interleukin 1β (IL-1β), macrophage inflammatory protein 2 (MIP-2), and elastase were also determined. CD11b expression at the end of the experiment was unchanged from the initial value in group R, whereas that in group C increased to almost double, and that in group S also showed a slight increase (P < 0.01). Serum TNF-α levels in groups R and S were lower than those observed in group C (P < 0.05). Serum IL-1β and MIP-2 levels in groups C and R tended to be higher than those in group S, although the difference was not statistically significant. Regarding elastase, group R showed a significantly lower value than group C and a higher value than group S (P < 0.05). Phosphodiesterase type 4 inhibition seems to suppress CPB-induced SIRS through the regulation of proinflammatory mediators in this rat model.     

Nonocclusive mesenteric ischemia after cardiopulmonary bypass

Nonocclusive mesenteric ischemia (NOMI) is a rare abdominal pathology caused by mucosal hypoperfusion without actual obstruction to the mesenteric arteries. We present a case of NOMI after a cardiopulmonary bypass operation. The patient was a 79-year-old woman with a history of hypertension and diabetes mellitus. A coronary bypass operation was performed with stable hemodynamic conditions, and continuous venovenous hemodialysis was performed on the second postoperative day because of renal insufficiency. After 24h of hemodialysis, the hematocrit level increased from 29.1% to 36.1%. The patient had some vague abdominal pain on the third postoperative day with abnormal laboratory values: leukocytes 17.10 × 10³/µl, creatine kinase 1085U/l, glutamic-oxyloacetic transaminase 6188U/l, and lactate dehydrogenase 8695U/l. Selective angiography showed diffuse stenosis of the superior mesenteric artery (SMA) without any occlusive findings on the major branches; the patient was therefore diagnosed with NOMI. An infusion of urokinase and prostaglandin E1 was started; however, disseminated intravascular coagulopathy had developed and the patient died on the 21st postoperative day as a result of multiple organ failure. The autopsy demonstrated extensive necrosis and hemorrhage in the small intestine without any occlusive findings on the major branches of the SMA.     

Bronchoconstriction during alveolar hypocapnia and systemic hypercapnia in dogs with a cardiopulmonary bypass

The roles of the alveolar and systemic CO₂ on the lung mechanics were investigated in dogs subjected to cardiopulmonary bypass. Low-frequency pulmonary impedance data (Z_L) were collected in open-chest dogs with an alveolar CO₂ level (FA_CO2)$(\text{F}{\text{A}}_{\text{C}{\text{O}}_2})$ of 0.2–7% and during systemic hypercapnia before and after elimination of the vagal tone. Airway resistance (R_aw), inertance (I_aw), parenchymal damping (G) and elastance (H) were estimated from the Z_L. The highest R_aw observed at 0.2% FA_CO2$\text{F}{\text{A}}_{\text{C}{\text{O}}_2}$, which decreased markedly up to a FA_CO2$\text{F}{\text{A}}_{\text{C}{\text{O}}_2}$ of 2% (212 ± 24%), and remained unchanged under normo- and hypercapnia (FA_CO2$\text{F}{\text{A}}_{\text{C}{\text{O}}_2}$ 2–7%). These changes were associated with smaller decreases in I_aw (−16.6 ± 3.7%), mild elevations in G (25.7 ± 4.7%), and no change in H. Significant increases in all mechanical parameters were observed following systemic hypercapnia; atropine counteracted the R_aw rises. We conclude that severe alveolar hypocapnia may contribute to minimization of the ventilation–perfusion mismatch by constricting the airways in poorly perfused lung regions. The constrictor potential of systemic hypercapnia is mediated by vagal reflexes.     

体外循环后全身炎性反应

全身炎性反应(SIRS)是体外循环手术后的常见并发症.体外循环中由于血液与体外循环装置中的气体界面及管道的作用,启动三个相交的血浆蛋白酶旁路的激活,这些旁路包括激肽-激肽释放酶系统、凝血-纤溶系统、补体系统,通过一系列的蛋白分解产生活化的致炎性介质,激活白细胞、内皮细胞及血小板,促使血管扩张及通透性增加.激活的细胞成分能分泌炎性介质包括细胞因子,增强这一反应过程,最终导致组织损伤及器官功能失调.     

Role of nitric oxide in regulation of systemic vascular resistance during and after cardiopulmonary bypass

Cardiopulmonary bypass (CPB) is known to result in the abnormal production of vasoactive substances contributing to the changes in hemodynamics such as systemic vascular resistance (SVR) during and after CPB. Nitric oxide (NO) is an inflammation-mediated vasoactive substance that plays a role in the whole-body inflammatory response induced by CPB. We evaluated the role of NO in the regulation of SVR during and after CPB. Fifteen patients underwent open-heart surgery for valvular heart disease. The perfusate blood temperature of CPB was set to 34°C. The plasma levels of NO metabolites (NO ₂ ⁻ +NO ₃ ⁻ ), prostaglandin E₂ (PGE₂), bradykinin (BK), and systemic vascular resistance index (SVRI) were measured before CPB and 0, 12, and 24 h after CPB. The plasma level of NO metabolites increased gradually after CPB (pre-CPB, 26.3 ±4.4; 0h, 33.7±6.5; 12 h, 49.8±11.1; 24 h, 43.1±7.5 μM). SVRI decreased gradually after CPB (pre-CPB, 2361±364; 0h, 2048±216; 12 h, 1590±308; 24 h, 1727±435 dyne·s·cm⁻⁵·m²). There was a significant inverse correlation between SVRI and the plasma level of NO metabolites as a whole (r=−0.674,P<0.0001). No significant correlations were observed between SVRI and the other vasoactive substances PGE₂ and BK. These findings demonstrated that NO production increased gradually during and after CPB in association with the decrease in SVR. Part of this study was presented at the 2nd annual meeting of the Japan Society for Adaptation Medicine on February 27, 1998     

兔体外循环中糖皮质激素受体变化及应用大剂量糖皮质激素的效应

本文应用兔体外循环（ＣＰＢ）模型研究ＣＰＢ中糖皮质激素受体（ＧＲ）的变化及早期应用大剂量糖皮质激素（ＧＣ）的效应。结果发现，兔胸腺高亲和力ＧＲ数目在ＣＰＢ６０ｍｉｎ较ＣＰＢ前显著下降（－３５％），ＣＰＢ中血浆ＧＣ浓度显著升高，同时伴有血浆磷脂酶Ａ２（ＰＬＡ２）活性和肺血管外含水量（ＥＶＬＷ／ＢＦＤＬ）显著升高；在ＣＰＢ前５ｍｉｎ静注琥珀酸钠氢化考的松２０ｍｇ／ｋｇ，虽使胸腺ＧＲ水平进一步下降（－６９％），但能显著提高ＣＰＢ期间血浆ＧＣ浓度，并能显著抑制血浆ＰＬＡ２活性和ＥＶＬＷ／ＢＦＤＬ的升高。提示ＣＰＢ能引起ＧＲ水平下降，从而降低ＧＣ效应；ＣＰＢ术中早期应用大剂量ＧＣ能在ＣＰＢ中ＧＲ减少的情况下维持或提高ＧＣ的效应，但其作用很可能并非完全通过高亲和力ＧＲ介导。     

Usefulness of low-priming-volume cardiopulmonary bypass circuits and dilutional ultrafiltration in neonatal open-heart surgery

In neonate open-heart surgery, cardiopulmonary bypass (CPB) with extreme hemodilution induces an increased capillary permeability and accumulation of extravascular fluid, resulting in organ dysfunction. We evaluated the effects of a reduced priming volume for CPB and dilutional ultrafiltration (DUF) during neonatal open-heart surgery. Nineteen consecutive neonates with complete transposition of the great arteries who underwent an arterial switch operation were retrospectively assigned into two groups: the high-priming-volume circuit group (group A, n = 9) and the low-priming-volume circuit group (group B, n = 10). Patients in group B underwent surgery with a miniaturized CPB circuit and using the DUF technique. The priming volume of group B was nearly two-thirds that of group A. The water balance value after CPB and surgery was significantly lower in group B (–126 ± 118ml, –116 ± 116ml) than in group A (88 ± 218ml, 83 ± 165ml). Systolic blood pressure just after CPB was higher in group B (67.9 ± 9.1mmHg) than in group A (55.4 ± 10.3mmHg). Postoperative ventilatory support was shorter in group B (45 ± 19h) than in group A (68 ± 27h). In neonatal cardiac surgery, low-priming-volume CPB circuits and DUF improve the water balance during surgery and may attenuate any inflammatory reaction, which would help preserve postoperative organ function.     

Morphological inspection of 80 consecutive Gyro pumps after cardiopulmonary bypass

 We have been using the Gyro centrifugal pump C1E3 for cardiopulmonary bypass in anticipation of high efficiency, low hemolysis, and antithrombogenicity of this pump. However, the clinical evaluation of this pump remains to be clarified, because it has been a short time since the pump appeared in clinical situations. The aim of the present study is to inspect and analyze the Gyro pumps morphologically after clinical use. We examined 80 consecutive pumps after cardiopulmonary bypass for 186 ± 67 min with a mean flow rate of 2.52 ± 0.22 l/min/m² at a mean rotational speed of 2485 ± 81.1 rpm. Although no abnormal findings were present in 79 pumps, one pump was found to contain effusion at the connection between the impeller body and the shaft. The extudate was supposed to be blood, based upon the results of X-ray spectrometer analysis. The cause was determined to be the upward deviation of the shaft off the impeller body. Scanning electron microscopy showed scratches on a part of the bottom housing and a smooth surface of both the male and female pivots of the pump. Surface profile measurement revealed that the deformity of the female pivots was 0.14 mm (top) and 0.05 mm (bottom). These observations suggest that the floating force and vibration by the rotating impeller acted on the joint zone between the alumina ceramic shaft and the polycarbonate impeller body, resulting in dissection of the adhesive agent from the polycarbonate. Although this abnormality may be rare, the structural design still may need to be improved. Received: November 9, 2001 / Accepted: February 4, 2002     

Poly-2-methoxyethylacrylate-coated bypass circuits reduce activation of coagulation system and inflammatory response in congenital cardiac surgery

Surface-coated cardiopulmonary bypass (CPB) has been shown to have excellent biocompatibility during cardiac surgery in adults, but there have been only a few reports demonstrating the efficacy of this coating for congenital cardiac surgery. We tested the efficacy of poly-2-methoxyethylacrylate (PMEA) coating for CPB circuits in congenital cardiac surgery. Eleven operative cases of ventricular septal defect were studied: group C (control: no coating, n = 5) and group P (PMEA coating, n = 6). The platelet count and beta-thromboglobulin (beta TG), fibrinogen (FBG), thrombin-antithrombin complex (TAT), and neutrophil elastase levels were measured during the operation. Postoperative chest tube drainage was analyzed and the surface of the artificial lung was observed with an electron microscope. Elevation of TAT and neutrophil elastase was suppressed in group P (P < 0.05). Observation of the artificial lung surface using an electron microscope clearly revealed fewer blood cells were adherent to the surface in group P. The FBG level and postoperative bleeding were relatively lower in group P, but there were no significant differences between groups. The platelet count and beta TG level were the same in both groups. We concluded that the PMEA-coated circuit reduces activation of the coagulation system and the inflammatory reaction in pediatric cardiac surgery.     

大鼠体外循环模型技术与实践

体外循环（CPB）技术经过50多年的不断发展，现已成为心脏外科常用的、安全有效的治疗手段，但由于非生理性的界面接触及血流改变，仍有许多与之相关的并发症困扰着临床。采用动物模型探讨CPB围手术期病理生理改变机制及各脏器功能保护策略是目前心脏外科面临的重要课题。大鼠模型具有费用低廉、装置简便、检测潜力大等优点，但由于动物体积较小，在装置设计和手术技术上有一定难度，所以在实际中尚未得到广泛应用。本文对大鼠CPB模型的技术要点进行总结分析，提出理想的、接近于临床的CPB小动物模型要求。