浅低温心脏不停跳人工瓣膜置换过程中心肌保护与局部炎症反应

背景：人工心脏瓣膜置换过程中心脏不停跳技术对机体的保护效果可能与减轻体外循环心脏手术诱发的炎症反应有关。目的：观察浅低温心脏不停跳手术对体外循环人工机械瓣膜置换患者心肌的保护作用与心肌局部炎症反应的关系。方法：将二尖瓣机械瓣膜置换患者随机分为对照组和实验组,对照组在中度低温心脏停跳下完成心脏瓣膜置换手术,实验组在浅低温心脏跳动下完成心脏瓣膜置换手术。结果与结论：两组瓣膜置换过程中心肌局部白细胞介素6、白细胞介素8、肿瘤坏死因子а、肌钙蛋白Ⅰ水平均较置换前显著升高;实验组白细胞介素6、白细胞介素8和肿瘤坏死因子а、肌钙蛋白Ⅰ水平升高程度显著低于对照组,表明心脏不停跳手术可减少体外循环期间心肌局部促炎性细胞因子的生成,减轻心肌局部炎症反应,保护心肌。两组体外循环结束时核转录因子κB表达增加,实验组较对照组增加幅度较小,说明浅低温心脏跳动手术有利于抑制心肌组织释放促炎性细胞因子。提示浅低温心脏不停跳手术在一定程度上减轻心肌的局部炎症反应,可能是该手术方式保护心肌的重要机制。     

老年患者浅低温心脏不停跳瓣膜置换中的心肌保护

背景:体外循环心内直视手术引起的心肌损害是术后并发症发生的重要原因,浅低温心脏不停跳技术有明显的心肌保护作用,对某些高危患者尤为有益.目的:观察浅低温体外循环心脏不停跳瓣膜置换对老年患者的心肌保护作用.方法:选择年龄≥60岁择期行二尖瓣人工瓣膜置换的风湿性心脏病患者30例,根据治疗方式分为2组,停跳组在中度低温心脏停跳下完成心脏瓣膜置换,不停跳组在浅低温心脏跳动中完成心脏瓣膜置换.结果与结论:在转机30 min、术中关闭右心房前,两组患者肿瘤坏死因子α、白细胞介素6,8、心肌肌钙蛋白Ⅰ浓度较转机前时升高(P < 0.05),其中以停跳组明显(P < 0.05).关闭右心房时两组核转录因子κB的表达增加,以不停跳组增加幅度较小(P < 0.05).提示浅低温心脏不停跳技术可以减轻老年患者体外循环心内直视手术过程中的心肌损害,该作用可能与减轻心肌的局部炎症反应有关.     

浅低温体外循环心脏不停跳瓣膜置换的肺保护

背景:浅低温体外循环心脏不停跳治疗可能减轻心内直视手术后肺损伤,但进一步的作用机制尚未明确。目的:探讨浅低温体外循环心脏不停跳下二尖瓣置换术肺保护效果。方法:纳入二尖瓣置换患者40例,随机数字表法均分为实验组与对照组,实验组采用浅低温体外循环心脏不停跳治疗,对照组采用中低温心脏停跳体外循环治疗。分别于置换开始和体外循环后30min两个时点收集支气管肺泡灌洗液,检测肿瘤坏死因子α、白细胞介素8、髓过氧化物酶水平;体外循环前及体外循环后30min分别取左右心房血测定中性粒细胞并计算跨肺差值;体外循环前、停机时、停机后1,8h查动脉血气分析,计算呼吸指数。结果与结论:①两组支气管肺泡灌洗液中肿瘤坏死因子α、白细胞介素8、髓过氧化物酶水平及中性粒细胞跨肺差值在体外循环后30min明显升高(P<0.01),但实验组明显低于对照组(P<0.05)。②两组呼吸指数在体外循环停机时、停机后1,8h各时点升高(P<0.05),但实验组升高明显低于对照组(P<0.05)。提示浅低温体外循环心脏不停跳能减轻二尖瓣置后的肺损伤,有较好的肺保护效果。     

浅低温体外循环心脏不停跳瓣膜置换的肺保护

背景：浅低温体外循环心脏不停跳治疗可能减轻心内直视手术后肺损伤,但进一步的作用机制尚未明确。目的：探讨浅低温体外循环心脏不停跳下二尖瓣置换术肺保护效果。方法：纳入二尖瓣置换患者40例,随机数字表法均分为实验组与对照组,实验组采用浅低温体外循环心脏不停跳治疗,对照组采用中低温心脏停跳体外循环治疗。分别于置换开始和体外循环后30min两个时点收集支气管肺泡灌洗液,检测肿瘤坏死因子α、白细胞介素8、髓过氧化物酶水平;体外循环前及体外循环后30min分别取左右心房血测定中性粒细胞并计算跨肺差值;体外循环前、停机时、停机后1,8h查动脉血气分析,计算呼吸指数。结果与结论：①两组支气管肺泡灌洗液中肿瘤坏死因子α、白细胞介素8、髓过氧化物酶水平及中性粒细胞跨肺差值在体外循环后30min明显升高（P〈0.01）,但实验组明显低于对照组（P〈0.05）。②两组呼吸指数在体外循环停机时、停机后1,8h各时点升高（P〈0.05）,但实验组升高明显低于对照组（P〈0.05）。提示浅低温体外循环心脏不停跳能减轻二尖瓣置后的肺损伤,有较好的肺保护效果。     

心脏不停跳瓣膜置换手术对心肌线粒体凋亡通路的影响

目的探讨浅低温心脏不停跳手术对体外循环瓣膜置换患者心肌线粒体凋亡通路的影响。方法 50例择期行人工机械瓣膜置换手术的患者,使用随机数字表法分为心脏停搏组(停跳组)和浅低温心脏不停跳组(不停跳组),每组25例,其中停跳组在中度低温心脏停搏下完成心脏瓣膜置换手术,不停跳组在浅低温心脏跳动下完成手术。分别在打开和关闭右心房时取右心房组织标本,使用实时荧光定量PCR检测心肌组织Cyto C、Caspase-3 m RNA表达,使用Western Blot检测心肌组织Cyto C、Caspase-3蛋白相对含量,TUNEL法观察心肌细胞凋亡情况。结果打开右心房时心肌Cyto C、Caspase-3 m RNA与蛋白表达二组间比较,差异均无统计学意义(P>0.05);二组在关闭右心房时比打开右心房时m RNA及蛋白表达均升高,差异有统计学意义(P<0.05),但不停跳组升高幅度较小(P<0.05)。结论 浅低温心脏不停跳手术在一定程度上可以减轻术中心肌线粒体凋亡通路的激活,减轻心肌损伤。     

浅低温体外循环心脏不停跳条件下瓣膜置换的肺保护

背景:浅低温体外循环心脏不停跳瓣膜置换可减轻术后肺损伤,与其可减轻中性粒细胞在肺部积聚,降低肿瘤坏死因子α、白细胞介素8等炎性因子水平有关,但其他方面的作用机制有待于进一步研究.目的:进一步探讨浅低温体外循环心脏不停跳二尖瓣置换术肺保护机制.方法:纳入二尖瓣置换患者40例,随机数字表法均分为2组.实验组采用浅低温体外循环心脏不停跳治疗,对照组采用中低温心脏停跳体外循环治疗.分别于开胸后和体外循环后30 min两个时点采集肺组织及静脉血,检测肺组织核转录因子κB表达水平及血液黏附分子CD11b/CD18荧光阳性百分率;体外循环前、体外循环30 min、停机时、停机后3,6,12 h取静脉血测定中性粒细胞弹性蛋白酶浓度;体外循环前、停机时、停机后1,8 h查动脉血气分析,计算呼吸指数.结果与结论:①两组肺组织核转录因子κB蛋白表达、CD11b/CD18荧光阳性百分率在体外循环后30 min明显升高(P < 0.01);但对照组明显高于实验组(P < 0.05).②两组血清中性粒细胞弹性蛋白酶浓度在体外循环 30 min、停机时、停机后3,6 h 4个时点明显升高(P < 0.01,P < 0.05),但对照组明显高于实验组(P < 0.01,P < 0.05).③两组呼吸指数在体外循环停机时、停机后1,8 h各时点升高(P < 0.01,P < 0.05),但对照组高于实验组(P < 0.05).提示浅低温体外循环心脏不停跳瓣膜置换可通过抑制肺部核转录因子кB活性,降低中性粒细胞表面CD11b/CD18表达及减少中性粒细胞释放弹性蛋白酶等机制,减轻术后肺损伤.     

浅低温体外循环心脏不停跳下心内直视手术的临床应用

目的：通过测定心脏不停跳与心脏停跳手术两组患者的血浆肌钙蛋白（cTn—Ⅰ）值以及心肌活检．评价心脏不停跳手术对心肌保护的效果。方法：选择40例心脏病患者于浅低温体外循环心脏不停跳下心内直视手术作为实验组，同期选择40例于低温心脏停跳下心内直视手术作为对照组，测定两组患者术前、术中、术后各时相的cTn—Ⅰ值，以及心肌活检病理进行比较研究。结果：两组术前cTn—Ⅰ值和心肌活栓病理显示心肌超微结构差异无显著性（P〉0．05）；转机后两组cTn—Ⅰ值均升高，对照组比实验组增高明显，差异有显著性（P〈0．05）：而心脏活检病理显示心肌超微结构上实验组优于对照组，差异有显著性（P〈0．05）。结论：浅低温体外循环心脏不停跳手术可明显减轻心肌缺血再灌注损伤．对心肌起到良好的保护作用     

猪供心离体不停跳保存的体外循环

背景:目前供心保存方法主要是单纯低温保存,安全时限为4～6 h,不可能长途运送,势必影响组织配型和有效的应用每一颗供心.因此,开展不停跳供心保存方法的研究很有必要.目的:建立猪供心离体浅低温不停跳保存的体外循环模型,为供心不停跳保存提供实验保障.方法:取体质量25～30 kg的广西巴马小型猪12头,随机分为2组.实验组取出有完整心包的供心后头臂干插灌注针连接体外循环灌注装置,左心引流,灌注流量60～80 mL/min,使心脏保持跳动8 h.对照组按常规方法摘取供心后用低温UW保护液保存心脏8 h.实验组生理记录仪监测心脏跳动心率及灌注压,保存1～8 h各时点抽取动脉血查血气分析、电解质.两组8 h后取心肌组织行ATP测定和超微结构检查.结果与结论:①实验组保存跳动8 h的心脏中,有1头猪出现短暂的2:1下传,其余的都保持完好跳动,②实验组保存跳动期间灌注压没有上升;血气分析pH和BE有逐渐降低的趋势;游离钙离子和钾离子有逐渐升高的趋势.⑨实验组ATP含量高于对照组(p<0.05).④实验组心肌超微结构仅有少数线粒体肿胀,大致接近正常的心肌结构.对照组心肌细胞内外水肿,较多空泡变性.结果提示,利用体外循环装置进行离体不停跳心脏保存是可行的,体外循环管理有其特殊性.     

浅低温心脏不停搏手术对减轻体外循环炎性反应的临床研究

目的　评价浅低温心脏不停搏手术对减轻体外循环炎性反应的效果。方法　先天性心脏病患者 4 4例 ,随机分为观察组 (不停搏组 )和对照组 (停搏组 )。观察组在浅低温 (31～ 34℃ )体外循环、心脏跳动状态下手术 ;对照组在冷晶体停搏、中度低温 (2 8～ 30℃ )体外循环下手术。分别在术前 (T1)、体外循环结束后即刻 (T2 )、3h(T3 )、6h(T4)、2 4h(T5)采集血标本 ,检测血清中肿瘤坏死因子 (TNF α)、白细胞介素 6 (IL 6 )、丙二醛 (MDA)含量。结果　体外循环结束后两组TNF α、IL 6、MDA含量均较术前明显升高 ;观察组IL 6含量在体外循环后各时点均低于对照组 (P <0 .0 1) ;观察组TNF α、MDA含量在体外循环后即刻、3h及 6h较对照组为低 (P <0 .0 5 ) ,在 2 4h两组无差异 (P >0 .0 5 )。结论　浅低温心脏不停搏手术可以减少细胞因子的释放 ,减轻体外循环炎性反应。     

浅低温体外循环心脏跳动二尖瓣置换术对心肌保护的体视学研究

目的用体视学定量法对比分析两种二尖瓣置换术（MVR）对心肌超微结构的影响，旨在为浅低温体外循环心脏不停跳心内直视手术对心肌保护效果作进一步客观的评价。方法将40例风湿性心脏病二尖瓣病变患者随机分为两组进行手术，20例在浅低温体外循环心脏不停跳下行MVR（不停跳组），20例在中低温冷血停搏液灌注心脏停跳下行MVR（停跳组）。两组均分别于体外循环前后切取少许心肌组织，用计算机图像分析系统对心肌超微结构的体视学定量进行对比分析。结果两组线粒体各参数在转流前差异无显著性（P均〉0.05）。停跳组在转流中、后线粒体平均直径（-↑Dmit）、平均截面积（-↑Amit）较转流前增大，但体密度（Vmit）、面数密度（Namit）、比表面（δmit）较不停跳组减少，差异均有显著性（P〈0.05或P〈0.01）；两组肌原纤维体密度（Vvmyo）在转流前、转流中变化不大，差异均无显著性（P均〉0.05），而转流后停跳组肌原纤维Vvmyo、比表面（δmyo）均较不停跳组减少，差异有显著性（P〈0.05和P〈0.01）。结论浅低温体外循环心脏跳动中心内直视手术是一种较接近生理状态的心肌保护方法，能最大程度地减轻心肌缺血、缺氧损伤，避免再灌注损伤，最大程度地保护心肌细胞形态结构的完整性，从而获得较理想的心肌保护效果。     

左卡尼汀强化St.Thomas No.2液对低温离体心脏的保存效果

背景:在心脏瓣膜置换中应用添加左卡尼汀的心脏停搏液可明显减轻心肌线粒体的脂质过氧化反应,保护心肌细胞.目的:观察加入左卡尼汀的St.Thomas No.2液对大鼠离体心脏低温保存的效果.方法:利用Langendorff 灌注装置建立SD大鼠离体心脏灌注和工作模型,随机分成4组,其中2组采用 St.Thomas No.2 液作为心脏停搏液与保存液分别保存心脏4 h、6 h,另2组采用添加左卡尼汀的St.Thomas No.2液作为心脏停搏液与保存液分别保存心脏4 h、6 h.结果与结论:与St.Thomas No.2 液保存4 h组比较,添加左卡尼汀的St.Thomas No.2液保存 4 h组心脏心率、冠状动脉流量、左心室收缩峰压和左心室内最大上升速率及心肌含水量、ATP含量差别无显著性意义(P > 0.05),但心肌酶漏出量明显减少(P < 0.05);添加左卡尼汀的St.Thomas No.2液保存 6 h组上述指标检测结果均优于St.Thomas No.2保存6 h组 (P < 0.05).提示左卡尼汀强化的St.Thomas No.2液可显著提高大鼠离体心脏的低温保存效果.     

左卡尼汀强化St.Thomas No.2液对低温离体心脏的保存效果

背景：在心脏瓣膜置换中应用添加左卡尼汀的心脏停搏液可明显减轻心肌线粒体的脂质过氧化反应,保护心肌细胞。目的：观察加入左卡尼汀的St.Thomas No.2液对大鼠离体心脏低温保存的效果。方法：利用Langendorff灌注装置建立SD大鼠离体心脏灌注和工作模型,随机分成4组,其中2组采用St.Thomas No.2液作为心脏停搏液与保存液分别保存心脏4h、6h,另2组采用添加左卡尼汀的St.Thomas No.2液作为心脏停搏液与保存液分别保存心脏4h、6h。结果与结论：与St.Thomas No.2液保存4h组比较,添加左卡尼汀的St.Thomas No.2液保存4h组心脏心率、冠状动脉流量、左心室收缩峰压和左心室内最大上升速率及心肌含水量、ATP含量差别无显著性意义（P〉0.05）,但心肌酶漏出量明显减少（P〈0.05）;添加左卡尼汀的St.Thomas No.2液保存6h组上述指标检测结果均优于St.Thomas No.2保存6h组（P〈0.05）。提示左卡尼汀强化的St.ThomasNo.2液可显著提高大鼠离体心脏的低温保存效果。     

Monitoring of fibrinolysis parameters during myocardial revascularization according to type of procedure.

The aim of the study was to assess the effect of cardiothoracic surgery on the dynamics of plasminogen, D-dimers and plasminogen activator inhibitor (PAI-I) during the first 24 h after surgery. The study included 14 patients operated with (on-pump) and 14 without (off-pump) the use of extracorporeal circulation (ECC). Blood sampling was carried out on induction of anesthesia (timepoint 1), on introduction of heparin (point 2) and protamine (point 3), at the end of surgery (point 4), and the next morning (point 5). Relative to point 1, the utilization of plasminogen at point 2 was 24% and 17% in the on-pump and off-pump groups, respectively (p=0.001 both). Increased D-dimer concentration from the baseline was more pronounced in the on-pump group (p=0.001). At point 5, D-dimer concentrations were comparable in both groups and different from baseline levels. PAI-I activity showed within-group differences from baseline at point 5 in the off-pump group (p=0.001), and at points 3 and 5 in the on-pump group (p=0.002 and 0.001, respectively). At point 5, the activity of PAI-I was comparable in both groups, yielding p=0.001 vs. baseline. Fibrinolysis was more pronounced and more dynamic in the on-pump group due to activation of the systemic inflammatory response induced by the use of ECC. In the off-pump group, fibrinolysis was a normal physiological response to the surgical procedure.     

Correlation between inflammatory response and markers of neuronal damage in coronary revascularization with and without cardiopulmonary bypass

Off-pump coronary artery bypass graft (CABG) surgery may reduce the inflammatory response and the neuronal damage associated with conventional CABG on cardiopulmonary bypass. The purpose of this study was to explore the protective effect of off-pump surgery by assessing plasma inflammatory and neuronal injury markers. Forty-one patients with coronary artery disease undergoing elective CABG were examined: 21 on-pump (Group I) and 20 off-pump (Group II). The perioperative release of interleukin-2 receptor (IL-2r), IL-6, tumor necrosis factor-alpha, S-100 protein (S-100) and neuron-specific enolase (NSE) were measured. Postoperative peak values of NSE (p < 0.001) and S-100 (p < 0.05) were significantly lower in Group II. IL-6 showed significantly lower values in off-pump patients (p < 0.001). A significant correlation was found between NSE and IL-6 (p < 0.001). In conclusion, off-pump surgery reduces the inflammatory response as well as the perioperative release of neuronal damage markers. Correlation between inflammatory activation and neuronal markers may suggest a link between inflammation and release of markers of neuronal clinical and subclinical injury.     

Secretory phospholipase A(2) activity and release kinetics of vascular tissue remodelling biomarkers after coronary artery bypass grafting with and without cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) has long been recognised as a main cause of a postoperative complex systemic inflammatory response after coronary artery bypass grafting (CABG). METHODS: We determined the kinetics of peripheral blood release of the novel inflammatory biomarkers secretory phospholipase A(2) (sPLA(2)), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) during the first 6 days following surgery in 16 patients undergoing CABG with (on-pump, n=9) or without (off-pump, n=7) CPB. Kinetic curves for these markers were compared to those of the well-known inflammatory parameters C-reactive protein (CRP) and fibrinogen. RESULTS: sPLA(2) activity exhibited a maximum value on day 2, then decreased until day 6 for both groups and in a similar manner as CRP levels. On the other hand, elevation of plasma levels of both MMP-9 and TIMP-1 occurred as early as on day 1 and remained at this level until day 6. No significant difference in kinetic characteristics (peak value, area under the curve, initial slope) between CABG with and without CPB was observed. CONCLUSIONS: These data show that the off- and on-pump groups did not show significantly different kinetics for the releases of all biomarkers studied, including sPLA(2) and biomarkers of the MMP-TIMP network. The off-pump procedure may therefore lead to global surgical trauma as important as CPB in terms of the systemic inflammatory process and matrix proteolysis pathway activation.     

Off-pump cardiac surgery abolishes complement activation

BACKGROUND: This prospective randomized study compared the inflammatory response in patients undergoing elective on-pump and off-pump coronary artery bypass grafting. PATIENTS AND METHODS: Forty-four patients undergoing elective coronary artery bypass grafting were recruited with 22 patients randomized to on-pump heart surgery and 22 patients to off-pump coronary bypass surgery. Plasma levels of C3bc, the terminal SC5b-9 complement complex, myeloperoxidase, beta-thromboglobulin and prothrombin fragment F1 + 2 were measured before the operation, intraoperatively, at termination of the operation, and two hours post-operatively. RESULTS: Complement was markedly activated in the on-pump group as indicated by a significant increase in C3bc and SC5b-9 (p < 0.001 for both), whereas no complement activation was seen in the off-pump group (p = 0.001 between the groups). In contrast, both groups showed significant activation of neutrophils, platelets and coagulation, as indicated by an early increase in myeloperoxidase and a post-operative increase in beta-thromboglobulin and F1 + 2, respectively. Notably, there were no intergroup differences with regard to neutrophil and platelet activation, whereas coagulation activation was more pronounced in the off-pump group (p < 0.01). CONCLUSIONS: Off-pump surgery completely eliminated the heart-lung machine-induced complement activation. Neutrophils and platelets were equally activated in both groups, whereas coagulation was enhanced post-operatively in the off-pump group.     

Effects of off-pump coronary artery bypass grafting on patient outcome.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with postoperative myocardial stunning, hypothermia, formation of microemboli, and systemic inflammatory response syndrome, all of which may prolong recovery from coronary artery bypass grafting (CABG) surgery. This study sought to compare outcomes in patients undergoing CABG off pump versus on pump. METHODS: Outcomes, including mortality and several morbidities, were reviewed in 1,623 on-pump patients and 683 off-pump patients. Morbidities assessed included postoperative bleeding, incidence of multiorgan dysfunction, and neurologic complications. Chi-square and t-test analysis were used to determine statistical significance. RESULTS: Mortality was 42% lower in the off-pump group than the on-pump group. Both critical care and total hospital length of stay were significantly shorter in the off-pump group. The incidence of postoperative bleeding requiring transfusion or a return to the operating room was reduced by 29% in the off-pump group and the incidence of multiorgan dysfunction was reduced by 31%. The off-pump patients also presented a significantly lower incidence of cerebral vascular accidents and seizures than on-pump patients. CONCLUSIONS: We conclude that there is an association between improved patient outcome and off-pump CABG surgery. The outcomes of this study show a statistically significant decrease in mortality, critical care length of stay, total hospital stay, incidence of bleeding requiring transfusion or return to the operating room, amount of blood transfused, incidence of multiorgan dysfunction, cerebral vascular accidents, and seizures in off-pump patients when compared with on-pump patients. Such results support the use of myocardial revascularization off pump as an alternative to CABG surgery on pump. CABG surgery off pump may allow a better postoperative clinical course in patients who are candidates for the procedure.