紫绀型先天性心脏病患儿的体外循环再氧合损伤

目的 通过控制体外循环启动时的吸入氧浓度,研究不同给氧浓度对紫绀型先天性心脏病再氧合损伤的影响及安全性.方法 紫绀型先天性心脏病患儿30例及非紫绀型先天性心脏病患儿10例,根据体外循环初始氧浓度分为4组:紫绀组1(G1),氧分压(PaO2)＜ 120 mm Hg(1 mm Hg =0.133kPa);紫绀组2(G2),PaO2 120 ～＜ 180 mm Hg;紫绀组3(G3),PaO2 180～ ＜250mmHg;非紫绀组(G4),PaO2＞200 mm Hg.体外循环前、体外循环开始后5 min、10 min、开放升主动脉后5 min、术后2h、24h检测血清心肌酶(CK-MB)、肌钙蛋白(cTnI)、白介素6(IL-6)、肿瘤坏死因子α(TNF-α)、超氧化物歧化酶(SOD)、8-异构前列腺素(8-ISO)和S100β蛋白(S100β)浓度,同时记录相应临床指标.结果 CK-MB、cTnI、IL-6、TNF-α、8-ISO、S100β术前4组间差异无统计学意义.体外循环开始后均上升,于体外循环停机前后达峰值,之后逐渐下降,在各时间点指标增高趋势为G3 ＞G2 ＞G1 ＞G4,4组间差异有统计学意义(P＜0.05).SOD在术前G4高于其他3组,差异有统计学意义(P＜0.05);体外循环开始后各组SOD水平均降低,于升主动脉开放后达最低值,之后逐渐升高,体外循环开始后5 min、10 min、开放升主动脉后5 min、术后2h4个时间点G3 ＜G2 ＜G1 ＜G4,组间差异有统计学意义(P＜0.05),术后24h G1、G2和G3组均低于G4组(P＜0.05),但3组间差异无统计学意义.SvO2、Lac、正性血管活性药物使用情况、机械通气时间和ICU住院时间3个紫绀组间差异无统计学意义,与非紫绀组相比差异有统计学意义(P＜0.05).4组患儿全部生存并顺利出院.结论 低氧启动体外循环可明显降低紫绀型先天性心脏病的再氧合损伤,在常规浅、中低温体外循环结合其他措施可有效降低再氧合损伤;对脑组织氧代谢有可能的潜在影响,在深低温及长时间体外循环供氧方式上还需进一步深入研究.     

心肺转流下犬心肌c-fos基因的表达

目的　研究冷心脏停搏液心肺转流 (CPB)下犬心肌损伤与c fos基因的表达。方法　10只犬分为实验组 (I组 ,n =6 )和对照组 (II组 ,n =4 )。I组动物施行全身低温心脏深低温 4℃St.Thomas液顺行灌注心停搏CPB ,II组动物在常温下施行不停跳并行循环。取不同时点的右心房组织进行免疫组化分析及透射电镜观察。结果　并行循环前 ,两组动物心肌细胞均无Fos阳性核染色 ;血管内皮细胞均有少量阳性染色。I组主动脉阻断 6 0min、主动脉开放 2 0及 4 0min心肌细胞核Fos阳性率持续增加 ;各时点血管内皮细胞Fos阳性率明显增加 ,且以主动脉开放 4 0min最高。II组并行循环 10 0min时 ,心肌细胞及血管内皮细胞Fos阳性率与并行前比较差异显著 (P <0 0 1) ,而显著低于I组同时点。I组开放主动脉 4 0min时心肌超微结构存在损伤征象。结论　 (1)冷心脏停搏液CPB下心肌存在一定的缺血 再灌注损伤 ;缺血和 (或 )低温诱导c fos的表达 ,再灌注则显著诱导心肌c fos的表达 ;(2 )血管内皮细胞c fos表达较心肌细胞迅速和强烈 ;(3)CPB本身亦可能诱导c fos基因的表达 ;(4)c fos表达增加与心肌损伤有关     

瑞芬太尼预处理对患儿体外循环诱导心肌缺血再灌注损伤的影响

目的观察瑞芬太尼预处理对先天性心脏病患儿体外循环诱导心肌缺血再灌注损伤的影响。方法先天性心脏病室间隔缺损患儿60例,年龄2-14岁,ASA分级Ⅰ级或Ⅱ级,心功能分级Ⅰ级或Ⅱ级,随机分为4组(n=15),对照组(C组)持续静脉输注瑞芬太尼0．2-0.5μg·kg-1·min-1;R1组、R2组、R3组主动脉阻断前分别以1、2、4μg·kg-1·min-1的速率静脉输注瑞芬太尼5 min,间隔5 min后重复输注瑞芬太尼,每组重复3次。于麻醉诱导前(T1)、主动脉阻断前即刻(T2)、主动脉开放即刻(T3)、主动脉开放后2 h(T4)、24 h(T5)、48 h(T6)采取血标本,检测心肌肌钙蛋白I(cTnI)的浓度和磷酸肌酸激酶同工酶(CK-MB)的活性。记录主动脉阻断前各时点的HR和MAP及主动脉开放后心脏复跳情况。结果与C组比较,R1组、R2组和R3组在主动脉阻断前各时点HR及MAP差异无统计学意义,R1组、R2组和R3组在T1、T2时cTnI及CK-MB差异无统计学意义(P>0．05),R3组在T3时cTnI降低,R2组、R3组在T3时CK-MB降低,R1组、R2组和R3组在T4、T5、T6时cTnI及CK-MB降低(P<0．05或0．01);与R1组比较,R3组在T4时cTnI降低(P<0．05)。结论瑞芬太尼预处理可减轻先天性心脏病患儿体外循环诱导的心肌缺血再灌注损伤。     

去白细胞血再灌注液对体外循环犬心肌缺血再灌注损伤的影响

目的探讨去白细胞血再灌注液对体外循环(CPB)犬心肌缺血再灌注损伤的影响及其机制。方法成年健康犬12条,根据再灌注液成分不同随机分为对照组(C组)和去白细胞血组(D组),每组6条。两组动物经麻醉和开胸后,建立CPB心肌缺血再灌注模型,阻断升主动脉60 min。于阻断40min时,自主动脉根部以2 ml·min-1·kg-1灌入常温晶体液或去白细胞血,持续20 min。分别于阻断前、阻断后30min及60min和开放后30min及60min取静脉血,检测血浆TNF-α、IL-1β、IL-6、IL-8浓度。并于阻断前、阻断后60 min和开放后60 min分别取心肌组织检测髓过氧化物酶(MPO)活性。结果与阻断前比较,阻断后各时点两组TNF-α、IL-1β和IL-8血浆浓度均升高,IL-6血浆浓度在开放后各时点升高(P<0．05);D组开放升主动脉后各时点TNF-α、IL-1β、IL-6和IL-8血浆浓度低于C组(P< 0．01);D组阻断后60 min和开放后60 min MPO活性低于C组(P<0．01)。结论去白细胞血再灌注液能减轻体外循环犬的心肌缺血再灌注损伤,抑制促炎性细胞因子可能是其作用机制之一。     

Heparin need of the patients with cyanotic congenital heart disease during cardiopulmonary bypass. Comparison of cyanotic, acyanotic, rheumatic and atherosclerotic subjects

Four groups of patients were studied. Group I: Congenital cyanotic heart disease (CCHD), consisting of 24 subjects aged 5 to 28 (1.4); 18 males and 4 females. Group II: Acyanotic congenital heart disease (ACHD), consisting of 34 patients aged 5 to 42 (20.1); 17 males and 17 females. Group III: Rheumatic heart disease (RHD), consisting of 30 patients aged 11-54 (42.4); 9 males and 21 females. Group IV: Atherosclerotic heart disease (AHD), consisting of 35 patients aged 36 to 65 (49.2); 33 males and 2 females. The haematocrit value (Hct) was the highest in the CCHD group. Total amount of heparin (mg/kg) used during cardiopulmonary bypass was 5.4 in CCHD, 4.66 in ACHD, 4.8 in RHD and 4.6 in AHD group. Mean protamine values was 4.02; 4; 4.03; and 4 respectively. Although the difference of Hct value was statistically different between CCHD and RHD group (p less than 0.001), heparin need was not (p less than 0.1). One-way analysis of variance (F test) showed no difference for heparin need between the four groups (F3.119 = 0.64). Prothrombin time (PT) and activated partial thromboplastin time (aPTT) showed a positive correlation (r = 0.36 and r = 0.25) with heparin need in CCHD group but no correlation was found in RHD group.     

雷米芬太尼后处理对心肺转流诱导犬心肌损伤和炎症因子的影响

目的 探讨雷米芬太尼后处理对心肺转流(CPB)诱导犬心肌损伤和炎症因子的影响.方法 健康成年雄性犬12只,随机均分为雷米芬太尼组(R组)和对照组(C组).两组动物经麻醉和开胸后,建立CPB心肌缺血-再灌注模型,阻断升主动脉60 min.R组于主动脉阻断55 min时自主动脉根部随温血灌注液持续输注雷米芬太尼5 min,速度为4μg·kg-1·min-1,灌注液输注速率2 ml·kg-1·min-1持续5 min.C组于相同时点行温血再灌注,灌注液输注速率同R组.分别于CPB前5 min(T0)、阻断升主动脉后30 min(T1)、开放升主动脉后5 min(T2)、停CPB 30 min(T3)和停CPB 2 h(T4)采集股动脉血,检测心肌肌钙蛋白I(cTnI)的浓度和血浆肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)、IL-8.记录主动脉开放后心脏自动复跳情况,电镜下观察心肌组织超微结构改变.结果 与T0时比较,两组cTnI、TNF-α在CPB后各时点均明显升高(P＜0.05或P＜0.01),升主动脉开放后各时点IL-6、IL-8均明显升高(P＜0.01).R组升主动脉开放后各时点cTnI、TNF-α、IL-6、IL-8均明显低于C组(P＜0.01).R组心肌组织结构损伤程度轻于C组.结论 雷米芬太尼后处理可抑制犬CPB诱导促炎细胞因子的释放,减轻心肌再灌注损伤.     

Leukocyte activation during cardiopulmonary bypass: limitations of the inhibitory mechanisms and strategies

Cardiopulmonary bypass, initiates a generalised response, which is primarily defensive in nature. This response is self regulated and terminated spontaneously. Obvious problems are complement and leucocyte activation, but several other cascades are also stimulated, which interact, accentuate or modulate this response. These supporting cascades include, release of inflammatory cytokines, an activation of kallikrein system, clotting and fibrinolytic mechanisms, and arachidonic acid metabolism. Because of an effective autoregulatory mechanism, only a small proportion of patients (<3%), undergoing cardiopulmonary bypass are adversely effected by this process. Prognosis of these patients is often unpredictable, but in general, high risk patients are likely to suffer most. A number of specific and non specific artificial measures have been introduced to control postperfusion problems, resulting from this process. These control measures are usually effective against a specific component of this generalised problem, and often fail to achieve desired effects. Efficacy of control measures is further limited by a continued activation of complement and leucocytes, via interactions between the mentioned inflammatory cascades. In view of these limitations, we have introduced certain modifications in our previously reported control strategy. These include an early identification of high risk and susceptible individuals and using specific inhibitors of complement activation for both initial and terminal stages.     

Inactivation of the MEK/ERK pathway in the myocardium during cardiopulmonary bypass

OBJECTIVES: A general pro-inflammatory response after cardiopulmonary bypass (CPB) may involve changes in signal transduction and in part be responsible for arrhythmias and myocardial dysfunction after cardiac surgery. The MEK/ERK (mitogen-activated protein kinase kinase/extracellular regulated kinase) pathway is common to many stimuli and may play a pivotal role in morbidity associated with CPB. We investigated the changes in MEK/ERK pathway and related enzymes after CPB in pigs. METHODS: We examined ventricular and atrial tissue from pigs before 90 minutes of normothermic CPB and after 90 minutes of post-CPB perfusion. The activities and protein levels of kinases MEK1/2, ERK1/2, a cellular tyrosine kinase (c-Src), protein kinase B (Akt), and the protein levels of mitogen-activated protein kinase phosphatase (MKP-1) were studied by immunoblotting ventricular and atrial myocardium lysates and labeling sections with antibodies that recognize the activated forms of the kinases and the phosphatase. Control pigs were subjected to sternotomy and heparinization but not CPB. RESULTS: We found a consistent inactivation of MEK/ERK pathway in both ventricular and atrial myocardium with an increase in MKP-1, a negative regulator of ERK1/2. The activities and protein levels of c-Src and Akt were not significantly modified before or after CPB, suggesting a certain degree of specificity for the MEK/ERK pathway. Such changes were not observed in controls. The decrease of ERK1/2 and MEK1/2 phosphorylation 90 minutes after termination of CPB (as well as the increase of nuclear MKP-1 protein levels) was also apparent by confocal microscopy. CONCLUSIONS: These results collectively reveal a prevalence of inhibitory mechanisms in the MEK/ERK signal transduction machinery in myocardium subjected to CPB.     

体外循环时心肌细胞上粘附分子的变化及抑肽酶对其表达的影响

目的：观察行心脏瓣膜置换术的病人在体外循环（CPB）前，后心肌细胞间粘附分-1(ICAM-1）及血管细胞间粘附分子－1（VCAM－1）的表达，并探讨抑肽酶对其表面的影响，方法：20例病人被随机均分为抑肽酶组和对照组，分别于手术开始及结束时取右心房心肌标本，采用免疫组化法检测心肌细胞及心肌血管内皮细胞上ICAM－1及VCAM－1的表达（IOD值）。结果：对照组心脏瓣膜我术病人CPB后心肌细胞上和心肌血管内皮细胞（EC）上ICAM－1及VCAM－1的表达较术前有明显增加（P＜0．05），而在抑肽酶组则无明显变化，组间比较，差异有具有显著意义，P＜0．05，结论：CPB时心肌细胞及心肌血管EC上ICAM－1及VCAM－1的表达增高，抑肽酶可通过抑制这些粘附分子的表达而减轻CPB所致的炎症反应。     

体外循环旁路洗入七氟醚对冠状动脉旁路移植术患者心肌损伤的影响

目的 评价体外循环(CPB)旁路洗入七氟醚对冠状动脉旁路移植术(CABG)患者心肌损伤的影响.方法 择期CPB下行CABG的患者40例,年龄50 ～ 64岁,体重53～90 kg,ASA分级Ⅱ或Ⅲ级,采用随机数字表法,将患者随机分为2组(n=20):对照组(C组)和七氟醚组(S组).S组于CPB开始即刻通过体外循环机洗入1.0％ ～2.0％七氟醚,持续到CPB结束,C组不给予七氟醚.于麻醉诱导后5 min(T0)、术后6 h(T1)、12 h(T2)及24 h(T3)时采集血样,测定血浆心肌肌钙蛋白I(cTnI)浓度和磷酸肌酸激酶同工酶(CK-MB)活性.于主动脉阻断前和CPB结束时取右心耳组织,电镜下观察心肌超微结构,并行心肌细胞线粒体损伤评分.结果 与C组比较,S组T2和T3时血浆cTnI浓度,CPB结束时心肌细胞线粒体损伤评分降低(P＜0.05),血浆CK-MB活性差异无统计学意义(P＞0.05).S组心肌病理学损伤较C组减轻.结论 CPB旁路洗入七氟醚可减轻CABG术患者的心肌损伤.     

Ultrafiltration during cardiopulmonary bypass: laboratory evaluation and initial clinical experience

Ultrafiltration during crystalloid hemodilution cardiopulmonary bypass (CPB) was evaluated in two groups of mongrel dogs: in one group during 2 hours of CPB with the heart empty and beating and in the other during 90 minutes of cold cardioplegic arrest followed by 30 minutes of recovery. In both groups, the accumulation of extravascular lung water was less in the dogs undergoing ultrafiltration than in control animals. In 10 patients with clinical evidence of severe fluid overload, ultrafiltration was employed during CPB. The amount of fluid removed ranged from 1,700 to 6,100 ml (mean, 3,240 +/- 1,481 ml [standard deviation]) and resulted in an average intraoperative fluid balance of -901 +/- 2,537 ml, a weight gain of 1.9 +/- 2.5 kg, and a decrease in extravascular lung water from 1,132 +/- 183 ml to 919 +/- 267 ml (p = 0.209). Ultrafiltration is a safe, effective means of removing body water and of preventing further accumulation of such water during hemodilution CPB.     

Fenoldopam in newborn patients undergoing cardiopulmonary bypass: controlled clinical trial

We determined if low dose fenoldopam in neonates already receiving conventional diuretics improves urine output, fluid balance, acute kidney injury incidence (AKI) and time to extubation. A prospective controlled clinical trial in a pediatric cardiac intensive care unit on 40 neonates undergoing cardiac surgery with cardiopulmonary bypass, excluding simple ventricular septal defect and atrial septal defect. Fenoldopam was infused at a low dose of 0.1 microg/kg/min soon after anesthesia induction and infusion prolonged for 72 h in 20 patients. Twenty neonates with standardized perioperative therapy except fenoldopam administration served as controls. Demographic, hemodynamic, daily urine output, creatinine, creatinine clearance, serum and urinary sodium and potassium were recorded. Inotropic score (IS) was calculated as a surrogate for the degree of hemodynamic impairment. Low dose fenoldopam infusion did not show beneficial effects in renal function. The treatment did not significantly affect IS value, AKI incidence, fluid balance control, time to sternal closure, time to extubation and time to intensive care unit discharge. Low dose fenoldopam in neonates undergoing cardiac surgery with CPB did not produce effects on urine output, fluid balance and AKI incidence. Fenoldopam was well tolerated and did not negatively affect hemodynamics and vasopressor support.