细胞因子对猴脑选择性超深低温断血流复苏缺血性脑保护的影响机制

目的观察猴脑选择性超深低温断血流复苏实验前后血清中细胞因子的动态变化，了解脑缺血后选择性超深低温复苏对缺血性脑保护的炎性机制。方法健康恒河猴4只，先阻断双侧颈总动脉血流10分钟，然后建立闭胸式脑局部体外循环，行一侧颈内动脉冷灌注，同侧颈内静脉回流。60分钟后恢复脑血流，自然复苏。应用ELISA法统一测定实验前后猴血清中IL-2、IL-10、TNF-α、IFN-γ的浓度。结果4只恒河猴术后安全复苏并长期存活，术后头颅MRI检查正常，术后神经功能评分无异常。4种细胞因子在灌注结束后较术前均明显增高（P〈0．05），24小时后恢复至术前水平，72小时测得值与术前无显著差异（P〉0．05）。Spearman相关系数统计显示不同时间点促炎因子IL-2、TNF-α、IFN-γ与抑炎因子IL-10之间呈明显的正相关。结论猴脑选择性超深低温断血流复苏可引起抗炎细胞因子与促炎细胞因子一过性增高，其中抑炎因子IL-10的明显表达和促炎因子之间互相抑制，互相作用，促使细胞因子网络维持动态平衡，从而减轻机体炎性反应同时抑制了脑缺血后机体炎性反应所引起的脑组织损伤，发挥脑保护作用。     

选择性深低温断血流对猴神经功能及神经元超微结构的影响

目的研究选择性深低温断血流对猴神经功能及神经元超微结构的影响。方法建立闭胸式脑局部体外循环,一侧颈内动脉冷灌注,同侧颈内静脉回流,60～80min后恢复脑血流,实验动物自然复苏。手术前后监测各主要脏器的血生化变化、观察神经功能并在预定的时间内处死动物行全脑电镜检查。结果7只猴中2只未能建立实验模型,其余5只均于术后复苏,其中4只长期存活;各主要脏器功能未见显著变化,术后神经功能评分无异常,神经元超微结构无明显异常。结论脑选择性深低温可明显提高脑对缺血缺氧的耐受性,延长血流阻断的时间。     

在深低温停循环中小预充量体外循环的脑保护效果

目的 观察在深低温停循环中小预充量体外循环的脑保护效果.方法 将实验动物分为假手术组(S组)、小预充量组(L组)、大预充量组(H组),建立联合脑微透析和体外循环(CPB)的动物模型.实验中进行微透析取样和生理指标监测,结束后取脑组织作组织学检测,用高效液相色谱法和CMA600分析仪检测微透析样品.结果 实验中,H组所用多巴胺和碳酸氢钠的量高于L组[(2.07±0.63)mg＞(1.12±0.47)mg;(14±3)ml＞(7±3)ml,P＜0.05].检测显示,H组的乳酸/葡萄糖和乳酸/丙酮酸比值在体外循环后高于L组(12.63±0.44＞3.71±1.31;13.14±1.37＞3.82±1.41,P＜0.05);H组的谷氨酸水平在实验后期高于L组(6.02±0.65＞2.21±0.72,P＜0.05);H组脑组织损伤程度明显重于L组.结论 深低温停循环时,与大预充量比较小预充量体外循环有显著的脑保护作用.     

The optimal flow rate for antegrade cerebral perfusion during deep hypothermic circulatory arrest

The aim of this study is to compare cerebral protection using antegrade cerebral perfusion (ACP) with various flow rates during deep hypothermic circulatory arrest (DHCA) in a piglet model. Twenty‐three piglets were randomized to five groups: the control group (n = 3), DHCA group (n = 5), ACP25 group (n = 5), ACP50 group (n = 5), and ACP80 group (n = 5). Three control piglets did not undergo operations. Twenty piglets underwent cardiopulmonary bypass (CPB) and DHCA for 60 min at 20°C. ACP was conducted at 0, 25, 50, and 80 mL/kg/min in the DHCA, ACP25, ACP50, and ACP80 group, respectively. Serum S‐100B protein and neuron‐specific enolase were monitored, and brain tissues were assayed for the activities of caspase‐3 and stained for the evidence of apoptotic cellular injury. Rise in serum S‐100B level (post‐CPB—pre‐CPB) in the ACP50 group was significantly lower than that in the ACP80 group (P = 0.001). Caspase‐3 levels were significantly elevated in the ACP80 group compared with the ACP25 (P = 0.041) and ACP50 group (P = 0.01), while positive terminal deoxyneucleotidyl transferase‐mediated biotin‐dUTP nick end labeling reaction scores in the ACP80 group were significantly higher than those in the ACP25 (P = 0.043) and ACP50 group (P = 0.023). Cerebral protection effects of ACP at 25 and 50 mL/kg/min were superior to that of ACP at 80 mL/kg/min as determined by cerebral markers, immunology, and histology.     

Neurologic recovery after deep hypothermic circulatory arrest in rats: A description of a long‐term survival model without blood priming

Brain injury associated with deep hypothermic circulatory arrest (DHCA) has been recognized in patients with congenital heart diseases and those undergoing aortic arch surgeries. However, the preclinical investigation of long‐term cerebral injury and recovery mechanisms related to DHCA has been restricted to a satisfactory recovery animal model with a determined recovery time. This study aimed to evaluate the feasibility of a long‐term surviving DHCA model without blood priming in rats, in order to investigate the pathophysiology of long‐term complications in further studies. Twelve Sprague‐Dawley rats were divided into 2 groups: sham group (n = 3) and DHCA group (n = 9). The DHCA group was further assigned to the surviving time of postoperative day 2, 14, and 30 (n = 3, respectively). The entire cardiopulmonary bypass (CPB) circuit consisted of a modified reservoir, a custom‐designed small‐volume membrane oxygenator, a roller pump and a heater/cooler. A 24‐G catheter was cannulated in the branch of the left femoral artery for arterial blood pressure monitoring. Cardiopulmonary bypass was established via the right external jugular vein–right atrium and tail artery. Rats were cooled to a rectal temperature of 18°C, followed by 30 minutes of DHCA with global ischemia. After re‐warming for approximately 40 minutes, the animals were weaned from the CPB at 35.5°C. Blood gas and hemodynamic parameters were recorded preoperatively and intraoperatively, and at 2, 14, and 30 days postoperatively. Thereafter, the brains were perfusion fixed and histologically analyzed. All DHCA processes were successfully achieved, and none of the rats died. Blood gas analysis and hemodynamic parameters at each time point were normal, and vital signs of all rats were stable. Histopathologic deficits in the hippocampus (pathological score, surviving hippocampal neurons, and Ki67‐positive neurons) manifested after 30 minutes of DHCA, which persisted for at least 14 days and recovered after 30 days. A novel and simple long‐term recovery model of DHCA in rats was established in the present study, and histopathologic deficits were observed after clinically relevant 30‐minute DHCA durations, in order to determine the 30‐day recovery time frame.     

选择性脑灌注对深低温停循环下的脑保护作用

目的总结并分析39例急性DeBakey Ⅰ型主动脉夹层患者在深低温停循环期间选择性脑灌注对脑保护的效果。方法经右锁骨下动脉或升主动脉插灌注管,右心房插引流管建立体外循环。全身降温至鼻咽温28℃时阻断并切开升主动脉,左、右冠状动脉开口灌注冷血心脏停跳液15—20ml／kg,完成近心端处理。鼻咽温18℃,肛温20℃时停体外循环,头部戴冰帽,取20°-30°头低位,阻断主动脉弓三大分支,右锁骨下动脉脑灌注5例,无名动脉和左颈总动脉插管脑灌注34例,灌注流量5—8ml／（kg·min）。结果体外循环转流时间206～256min,平均（230±30）min;主动脉阻断时间95—155min,平均（118±23）min;选择性脑保护灌注时间39—59min,平均（53±14）min。手术死亡3例（7．69％）。一过性精神障碍2例（5．13％）。结论选择性脑灌注能显著降低深低温停循环手术的脑部并发症,有助于改善DeBakey Ⅰ型主动脉夹层患者的手术预后。     

婴儿深低温体外循环术后肺表面活性物质的变化

目的 比较婴儿先天性心脏病在深低温停循环(DHCA)或深低温低流量(DHLF)下行心内直视手术后肺表面活性物质(PS)活性水平的变化. 方法 根据采用的体外循环(CPB)方法不同,将20例室间隔缺损伴肺动脉高压的婴儿分为DHCA组和DHLF组,每组10例.测定CPB前,CPB结束5分钟和2小时时PS活性水平的饱和卵磷脂/总磷脂(SatPC/TPL)和饱和卵磷脂/总蛋白(SatPC/TP)值和肺静态顺应性. 结果 DHLF组术后住ICU时间明显长于DHCA组(P<0.05), DHLF组术后SatPC/TPL、SatPC/TP和肺静态顺应性下降的幅度均明显大于DHCA组(P<0.01). 结论 DHLF较DHCA更能引起PS活性水平的降低,从而引起更严重的肺损伤.     

深低温停循环主动脉夹层手术后高胆红素血症的危险因素分析

目的研究深低温停循环(deep hypothermic circulatory arrest,DHCA)主动脉夹层手术后高胆红素血症的危险因素。方法回顾性分析青岛大学附属医院177例DHCA下Stanford A型夹层手术患者资料,男126例,女51例,年龄≥18岁,ASA均为Ⅳ级。将患者分为两组:高胆红素血症组(HB组,n=96),血浆总胆红素(total bilirubin,TBIL)51.3μmol/L;正常组(N组,n=81),TBIL≤51.3μmol/L。采用Logistic回归分析高胆红素血症的危险因素。结果术后高胆红素血症发生率为54.2%。阻断时间(OR=1.026,95%CI 1.005～1.048,P=0.017),术中输红细胞(OR=1.192,95%CI 1.032～1.378,P=0.017),术前TBIL(OR=1.098,95%CI 1.038～1.161,P=0.001)是DHCA主动脉夹层手术后高胆红素血症的独立危险因素。采用ROC曲线分析显示,阻断时间、术中输红细胞、术前TBIL的临界值分别为93.5min、3.0U、21.3μmol/L。HB组术后输注血浆量明显多于N组(P0.05)。HB组存活率明显低于N组(81.3%vs 92.6%,P=0.03)。结论DHCA主动脉夹层手术后高胆红素血症的发生率较高,预后较差。阻断时间93.5min、术中输注红细胞3.0U、术前TBIL21.3μmol/L是高胆红素血症发生的危险因素。     

Exploring effects of remote ischemic preconditioning in a pig model of hypothermic circulatory arrest

Objectives. During aortic and cardiac surgery, risks for mortality and morbidity are inevitable. Surgical setups involving deep hypothermic circulatory arrest (DHCA) are effective to achieve organ protection against ischemic injury. The aim of this study was to identify humoural factors mediating additive protective effects of remote ischemic preconditioning (RIPC) in a porcine model of DHCA. Design. Twenty-two pigs were randomized into the RIPC group (n?=?11) and the control group (n?=?11). The RIPC group underwent four 5-minute hind limb ischemia-reperfusion cycles prior to cardiopulmonary bypass and DHCA. All animals underwent identical surgical procedures including 60?min DHCA at 18?°C. Blood samples were collected from vena cava and sagittal sinus at several time points. After the 8-hour follow-up period, the brain, heart, and kidney tissue samples were collected for tissue analyses. Results. Serum levels of brain damage marker S100B recovered faster in the RIPC group, after 4?hours of the arrest, (p?Conclusions. The faster recovery of S100B, lower systemic lactate levels and favourable regional antioxidant response suggest possible neuronal cellular and mitochondrial protection by RIPC, whereas better cardiac index underlines functional effects of RIPC. The exact humoural factor remains unclear.