单唾液酸神经节苷脂对体外循环大鼠炎性反应的影响

目的 评价单唾液酸神经节苷脂(GM1)对体外循环(CPB)大鼠炎性反应的影响.方法 成年雄性SD大鼠24只,体重350 ～ 450 g,4～6月龄,采用随机数字表法,将其分为3组(n=8):假手术组(S组)、CPB组、CPB+ GM1组(G组).G组在预充液中加入GM1 20 mg/kg;C组预充液中加入等容量生理盐水.CPB组和G组于CPB停止后3h时,S组于相应时点,取颈静脉血样,采用ELISA法测定血浆神经元特异性烯醇化酶(NSE)和S-100β蛋白浓度,采用放射免疫分析法测定血浆TNF-α和IL-6浓度;取海马组织,采用Western blot法检测海马基质金属蛋白酶-9(MMP-9)、IL-10表达及NF-κB活性.结果 与S组比较,CPB组和G组血浆NSE、S-100β蛋白、TNF-α和IL-6浓度升高,海马MMP-9表达上调,NF-κB活性增强,IL-10表达下调(P＜0.05);与CPB组比较,G组血浆NSE、S-100β蛋白、TNF-α和IL-6浓度降低,海马MMP-9表达下调,NF-κB活性减弱,IL-10表达上调(P＜0.05).结论 GM1减轻CPB诱发大鼠脑损伤的机制可能与抑制中枢和全身炎性反应有关.     

The systemic inflammatory response to cardiopulmonary bypass

Although our understanding of the basic pathophysiology of systemic inflammatory response to CPB has significantly advanced in the last 2 decades, these experimentally derived ideas have yet to be fully integrated into clinical practice. Treatment of the systemic inflammatory response to CPB is also confounded by the fact that inhibition of inflammation might disrupt protective physiologic responses or result in immunosuppression. Although it is unlikely that no single therapeutic strategy will ever be sufficient in of itself to totally prevent CPB-associated morbidity, the combination of multiple pharmacologic and mechanical therapeutic strategies, each selectively targeted at different components of the inflammatory response, may eventually result in significantly improved clinical outcomes following cardiac surgery.     

The systemic inflammatory response syndrome and cardiopulmonary bypass

Cardiac surgery using cardiopulmonary bypass (CPB) provokes a systemic inflammatory response. This is mainly triggered by contact activation of blood by artificial surfaces of the extracorporeal circuit. Although often remaining sub-clinical and resolving promptly at the end of CPB, in its most extreme form this inflammatory response may be associated with the development of the systemic inflammatory response syndrome (SIRS) that can often lead to major organ dysfunction (MODs) and death. Here, we review the pathophysiology behind the development of this "whole body" inflammatory response and some of the methods currently used to minimise it.     

Inducible nitric oxide production is an adaptation to cardiopulmonary bypass-induced inflammatory response

BACKGROUND: Cardiopulmonary bypass (CPB) increases nitric oxide (NO) production by the activation of NO synthases (NOS). However, the role of NO from inducible NOS (iNOS) in CPB-induced inflammatory response remains unclear. We examined the effect of a selective iNOS inhibitor, aminoguanidine, on CPB-induced inflammatory response in a rat-CPB model. METHODS: Adult Sprague-Dawley rats underwent 60 minutes of CPB (100 mL x kg(-1) x min(-1), 34 degrees C). Group A (n = 10) received 100 mg/kg of aminoguanidine intraperitoneally 30 minutes before the initiation of CPB, and group B (n = 10) served as controls. RESULTS: There were significant time-dependent changes in plasma interleukin (IL)-6, IL-8, nitrate + nitrite, the percentage ratio of nitrotyrosine to tyrosine (%NO2-Tyr, an indicator of peroxynitrite formation), and respiratory index (RI). Three hours after CPB termination, IL-6, IL-8, and RI were significantly higher in group A (IL-6, 397.5+/-80.6 pg/mL; IL-8, 26.99+/-6.57 ng/mL; RI, 1.87+/-0.31) than in group B (IL-6, 316.5+/-73.9 pg/mL, p <0.05; IL-8, 17.21+/-3.12 ng/mL, p < 0.01; RI, 1.57+/-0.24, p < 0.05) although nitrate + nitrite (31.8+/-4.1 micromol/L) and %NO2-Tyr (1.15%+/-0.20%) were significantly lower in group A than in group B (nitrate + nitrite, 50.2+/-5.0 micromol/L, p < 0.01; %NO2-Tyr, 1.46%+/-0.21%, p < 0.01). Western immunoblot analysis from lung tissue of group A identified marked iNOS inhibition without inhibiting endothelial-constitutive NOS, and neutrophil accumulation in the lung specimens was significantly greater in group A (6.5+/-0.7/alveoli) than in group B (4.4+/-0.4/alveoli, p < 0.01). CONCLUSIONS: These results suggest that NO production from iNOS may be an adaptive response for attenuating the CPB-induced inflammatory response.     

Aprotinin and the systemic inflammatory response after cardiopulmonary bypass

Cardiopulmonary bypass is associated with a systemic inflammatory response, a spectrum of pathophysiologic changes ranging from mild organ dysfunction to multisystem organ failure. Complications include coagulation disorders (bleeding diathesis, hyperfibrinolysis) from platelet defects and plasmin activation, as well as pulmonary dysfunction from neutrophil sequestration and degranulation. Diverse injuries are a consequence of multiple inflammatory mediators (complement, kinins, kallikrein, cytokines). Both plasmin and kallikrein amplify the inflammatory response by activating components of the contact activation system. The full-Hammersmith (high dose) of aprotinin, a serine protease inhibitor approved for reducing blood loss and transfusion requirements in cardiopulmonary bypass, inhibits kallikrein and plasmin, resulting in suppression of multiple systems involved in the inflammatory response. Specifically, inhibition of factor XII, bradykinin, C5a, neutrophil integrin expression, elastase activity, and airway nitric oxide production are observed. Clinical correlates include reduced capillary leak, preserved systemic vascular resistance and blood pressure, and improved myocardial recovery following ischemia. Overall, evidence indicates that aprotinin attenuates the systemic inflammatory response associated with cardiopulmonary bypass.     

甲基强的松龙预先给药对体外循环诱发心脏手术患者肠粘膜屏障损伤的影响

目的 评价甲基强的松龙预先给药对体外循环(CPB)诱发心脏手术患者肠粘膜屏障损伤的影响.方法 择期心脏手术患者90例,年龄30-50岁,性别不限,体重50-75 kg,心功能分级Ⅰ或Ⅱ级,采用随机数字表法,将患者随机分为3组(n=30):非CPB对照组(Ⅰ组)、CPB对照组(Ⅱ组)和CPB甲基强的松龙组(Ⅲ组).Ⅲ组于手术开始前和CPB开始前分别静脉注射甲基强的松龙10mg/kg,Ⅰ组和Ⅱ组静脉注射等量生理盐水.于麻醉诱导前(T1)、CPB开始前(T2)、CPB 30 min(T3)、CPB结束后30min(T4)、术后120 min(T5)时采集中心静脉血样测定血浆内毒素浓度;记录术后7d内感染发生情况.结果 3组Tl时血浆内毒素浓度比较差异无统计学意义,且均在正常范围;与Ⅰ组比较,Ⅲ组T3、T4和T5时血浆内毒素浓度升高,术后感染发生率升高(P＜0.05);与Ⅱ组比较,Ⅲ组T3、T4和T5时血浆内毒素浓度降低,术后感染发生率降低(P＜0.05).结论 甲基强的松龙预先给药可减轻心脏手术患者CPB所致的肠粘膜屏障功能损害.     

两种氧合器对心肺转流炎症反应的影响

目的动态监测室间隔缺损修补术患者在心肺转流(CPB)各时段血清可溶性细胞间粘附分子(sICAM-1)、可溶性E-选择素(sE-selection)及肿瘤坏死因子α(TNF-α)的变化规律,并比较西京-90鼓泡式氧合器和希健-Ⅱ膜式氧合器对其的影响。方法选择择期行室间隔缺损修补术的患者30例,随机均分为鼓泡式氧合器组(B组)和膜式氧合器组(M组)。所有患者分别在麻醉后CPB开始前(T1)、主动脉阻断开放前(T2)、CPB结束时(T3)、术后2h(T4)、6h(T5)、24h(T6)及48h(T7)取静脉血5ml用ELISA法测定sICAM-1、sE-selection及TNF-α的浓度。结果两组患者血清中的TNF-α于T2时开始显著升高,T4时达到峰值(P<0·01)。sICAM-1于T5时开始升高,T6时达峰值。sE-selection于T4时开始升高,T5时达峰值(P<0·01)。M组大部分时点TNF-α、sICAM-1、sE-selection的浓度均低于B组。结论希健-Ⅱ膜式氧合器引起的炎症反应较轻。     

Comparative effectiveness of methylprednisolone and zero-balance ultrafiltration on inflammatory response after pediatric cardiopulmonary bypass

Studies have demonstrated that systemic inflammatory response syndrome (SIRS) remains one of the major causes of cardiopulmonary bypass (CPB)-associated organ injury during pediatric cardiac surgery. The purpose of this investigation was to compare the effectiveness of methylprednisolone (MP) and zero-balance ultrafiltration (ZBUF) on SIRS during pediatric CPB. Thirty infants undergoing open-heart surgeries were randomized to receive either MP in the priming solution (group M, n = 15) or ZBUF during CPB (group Z, n = 15). All the patients survived. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) were measured before CPB (T1), 5 min after the start of CPB (T2), at the termination of CPB (T3), the fourth hour (T4), and the eighth hour (T5) postoperatively. The results showed that the plasma concentrations of TNF-alpha in the Z group were significantly less than those in the M group at T4 and T5 (P < 0.05), and the plasma concentrations of IL-6 were significantly less than those in the M group at T4 (P < 0.05); the plasma concentrations of IL-8 in the Z group were significantly less than those in the M group at T5 (P < 0.05). There was no difference between two groups on the plasma concentrations of IL-10. The duration of postoperative mechanical ventilation was (9.6 +/- 0.8 h) in the M group and (7.8 +/- 0.4 h) in the Z group (P < 0.05). This study showed that application of ZBUF is more effective to decrease the level of inflammatory mediators including TNF-alpha, IL-6, and IL-8 than administration of MP after pediatric CPB.     

The effects of cardiopulmonary bypass temperature on inflammatory response following cardiopulmonary bypass.

OBJECTIVES: The inflammatory response to cardiopulmonary bypass is believed to play an important role in end organ dysfunction after open heart surgery and may be more profound after normothermic systemic perfusion. The aim of the present study was to investigate the effects of cardiopulmonary bypass temperature on the production of markers of inflammatory activity after coronary artery surgery. METHODS: Forty-five low risk patients undergoing elective coronary artery surgery were prospectively randomized into three groups: hypothermia (28 degrees C, n = 15), moderate hypothermia (32 degrees C, n = 15), and normothermia (37 degrees C, n = 15). All patients received cold antegrade crystalloid cardioplegia and topical myocardial cooling with saline at 4 degrees C. Serum samples were collected for the estimation of neutrophil elastase, interleukin 8, C3d, and IgG under ice preoperatively, 5 min after heparinisation, 30 min following start of CPB, at the end of CPB, 5 min after protamine administration, and 4, 12 and 24 h postoperatively. RESULTS: Patients were similar with regard to preoperative and intraoperative characteristics (age, sex, severity of symptoms, number of grafts performed, aortic cross clamp time, cardiopulmonary bypass time). Neutrophil elastase concentration increased markedly as early as 30 min after the onset of cardiopulmonary bypass and peaked 5 min after protamine administration. Levels were not significantly different between the three groups. A similar finding was apparent for C3d release. Interleukin 8 concentrations also demonstrated a considerable increase related to cardiopulmonary bypass in all groups, but there was a significantly more rapid decline in interleukin 8 concentrations in the normothermic group in the postoperative period. Eluted IgG fraction showed a much earlier peak concentration than the other markers, occurring within 30 min of the start of cardiopulmonary bypass. Levels reached a plateau, before declining soon after the end of bypass and remained higher than preoperative values at 24 h. There was no difference between the three groups. The cumulative release of all markers was calculated from the concentration-time curves, and was not statistically different between groups. CONCLUSION: Normothermic systemic perfusion was not shown to produce a more profound inflammatory response compared to hypothermic and moderately hypothermic cardiopulmonary bypass.     

The systemic inflammatory response after cardiac surgery with cardiopulmonary bypass in children

Paediatric cardiac surgery often requires cardiopulmonary bypass (CPB) during the surgical intervention. CPB is known to elicit a systemic inflammatory response with activation of the complement and coagulation systems, stimulation of cytokine production, cellular entrapment in organs, neutrophil activation with degranulation, platelet activation, and endothelial dysfunction. These changes are associated with a risk of postoperative organ dysfunction and increased morbidity and mortality in the postoperative period. Clinical studies have concentrated on measurement of inflammatory markers and mediators in peripheral blood, where the systemic inflammatory response in the paediatric cardiac patient seems to be different from the adult case. Looking at the organ level, experimental studies have the advantage of providing information contributing to a better understanding of the pathological events that may lead to the deteriorated organ function. This review focuses on the systemic inflammatory response after cardiac surgery with CPB in children and experimental CPB models.     

米力农对心肺转流促炎细胞因子反应及心肌损伤的影响

目的探讨米力农对心肺转流(CPB)诱发的促炎细胞因子反应及心肌损伤的影响。方法24例择期瓣膜替换术病人,随机分成米力农组(M组)和对照组(C组),每组12例。麻醉诱导开始前,M组给予米力农30μg/kg负荷量静注,继以0.5μg·kg-1·min-1持续静脉输注;C组以相同速度输注等量生理盐水。分别于术前(T1)、CPB60min(T2)、CPB结束后2h(T3)、4h(T4)及24h(T5)各时间点测定动脉血中下列各项指标:肿瘤坏死因子α(TNFα)、白细胞介素6(IL6)、白细胞介素8(IL8)、血浆过氧化脂质(LPO)、心肌肌酸激酶同工酶(CKMB)。结果与T1比较,其余各时点两组TNFα、IL6、IL8、LPO、CKMB均明显升高(P<0.05或P<0.01),但M组升高明显低于C组(P<0.05)。结论米力农能有效抑制CPB诱发的促炎细胞因子反应和心肌损伤。     

The effect of lower limb ischaemia-reperfusion on intestinal permeability and the systemic inflammatory response.

OBJECTIVES: a relationship has been demonstrated between increased intestinal permeability, endotoxaemia and the development of the systemic inflammatory response syndrome (SIRS) after aortic surgery. The aim of this study was to evaluate whether isolated lower limb ischaemia-reperfusion (I/R) injury affects intestinal mucosal barrier function and cytokine release. PATIENTS AND METHODS: four groups of patients were investigated, group I, patients with critical limb ischaemia (CLI) undergoing infra-inguinal bypass surgery (n=18); group II, patients with intermittent claudication (IC) undergoing infra-inguinal bypass surgery (n=14); group III, patients with CLI unsuitable for arterial reconstruction, undergoing major amputation (n=12); and group IV, patients undergoing carotid endarterectomy for symptomatic carotid stenosis (n=13). Intestinal permeability, endotoxaemia and urinary soluble tumour necrosis factor receptors were assessed (p55TNF-R). RESULTS: an increase in intestinal permeability was observed on the 3rd postoperative day only in CLI group. This was found to correlate with arterial clamp time. Patients who had a femoro-distal bypass had significantly higher intestinal permeability compared to those who had femoro-popliteal bypass. Endotoxaemia was not detected in any of the groups. Postoperative urinary p55TNF-R concentrations were significantly higher in CLI group compared to the other groups. These did not correlate with the increased intestinal permeability. CONCLUSIONS:our results support the hypothesis that revascularisation of critically ischaemia limbs leads to intestinal mucosal barrier dysfunction and cytokine release. They also suggest that the magnitude of the inflammatory response following I/R injury is related to the degree of initial ischaemia.     

术前单次小剂量甲强龙对经皮肾镜碎石取石术后全身炎症反应综合征影响的回顾性研究

目的探讨术前单次小剂量甲强龙对经皮肾镜碎石取石术(PCNL)术后全身炎症反应综合征(SIRS)的影响。方法回顾性收集2019年1月至2021年5月期间在我院泌尿外科接受PCNL的患者资料315例,经排除最终纳入237例。根据术前是否使用甲强龙分为两组,对比两组术后SIRS的发生率及其他预后指标。结果甲强龙组患者120例,对照组117例,两组患者术前基线临床资料无统计学差异(P>0.05)。甲强龙组术后2小时降钙素原(PCT)及超敏C反应蛋白(HSCRP)、术后1天PCT及HSCRP低于对照组(P<0.05);甲强龙组术后当天发热率、术后住院时间低于对照组(P<0.05);两组术后SIRS发生率、术后血培养阳性率、脓毒血症发生率、重症监护病房(ICU)住院率均无统计学差异。结论术前单次小剂量甲强龙可降低PCNL患者术后PCT及HSCRP水平、手术当天发热率、术后住院时间,但对术后SIRS的发生无预防作用。     

小剂量氯胺酮对体外循环促炎细胞因子反应及心肌损伤的影响

目的 探讨小剂量氯胺酮对体外循环（CPB）诱发的促炎细胞因子反应及心肌损伤的影响。方法 20例择期瓣膜替换术病人,随机分成氯胺酮组（n＝10）和对照组（n＝10）。氯胺酮组于麻醉诱导和转流开始时按1mg.kg^-1静注氯胺酮,对照组则采用等量生理盐水注射。分别于术前（T1）、CPB60min（T2）、CPB结束后2h（T3)、4h(T4)及24h（T5）各时间点测定动脉血中下列各项指标;肿瘤坏死因子－α（TNF－α）、白细胞介素－6（IL－6）、白细胞介素－8（IL－8）、血浆过氧化脂质（LPO）、心肌肌酸酶同工酶（CK－MB）。结果 与术前（T1）比较,两组TNF－α、IL－6、IL－8、LPO、CK－MB均明显升高（P＜0．05或0．01）;但氯胺酮组T2－T5TNF－α、IL－6、IL－8浓度、T3LPO浓度和T3、T4、CK－MB活性均显著低于对照组（P＜0．05）。结论 小剂量氯胺酮能有效抑制CPB诱发的促炎细胞因子反应和心肌损伤。     

术中调节全身炎性反应对预防性镇痛的影响

目的 观察老年骨科患者术中使用乌司他丁调节全身炎性反应对预防性镇痛的影响.方法 80例老年骨科患者利用随机数字表及随机数余数分组方法被随机分入全麻+乌司他丁组(A组)、全麻+硬膜外麻醉组(B组)、全麻+乌司他丁复合硬膜外麻醉组(C组)、或单纯全麻组(D组).A组在切皮前予乌司他丁20万U,然后以20万U/h持续泵入至手...     

乌司他丁对体外循环期间胃肠循环及炎性因子的影响

目的 探讨乌司他丁对心内直视手术病人胃肠循环及炎性反应的影响。方法 选择30例风心病心内直视瓣膜置换术病人,麻醉诱导后插入胃管,随机分为对照组(C组)和乌司他丁组(U组);U组给予乌司他丁1.2万u·kg-1,于麻醉诱导后缓慢静注半量,另半量加入预充液中随转机进入体内。对照组用等量生理盐水代替。分别予CPB前(T0),主动脉阻断30min(T1),停机60min(T2),术后6h(T3)测定PaCO2和胃粘膜PCO2(PiCO2)、计算PiCO2与PaCO2之差P(i-a)CO2和胃粘膜pH(pHi),同时取颈内静脉血测,TNF-α和IL-6浓度。结果 pHi:C、U两组T1、T2显著降低(P<0.01),T3基本恢复至T0水平(P>0.05),两组间比较U组T1、T2、T3显著升高(P<0.05)。P(i-a)CO2、TNF-α和LI-6:U、C两组与T0比较T1、T2、T3显著升高(P<0.01),两组间比较U组T1、T2、T3显著下降(P<0.01)。结论 乌司他丁可改善CPB期间胃肠微循环,保护胃粘膜,还可减轻CPB期间促炎性细胞因子,TNF-α、IL-6的生成和释放,从而减轻CPB病人机体的急性炎症反应。     

白细胞滤除对犬体外循环诱发全身炎性反应的影响

目的探讨白细胞滤除对犬体外循环（CPB）诱发全身炎性反应的影响。方法蒙古犬12只，体重25—30kg，随机分为2组（n=6）：对照组（C组）和白细胞滤除组（LD组），C组不使用白细胞滤器，LD组将滤器安装于CPB的静脉回流端，在CPB2min时打开滤器5min。分别于CPB前即刻（T0）、阻断升主动脉后即刻（T1）、阻断升主动脉30min（T2）、开放升主动脉后5min（T3）、停CPB即刻（T4）、停CPB2h（T5）自股静脉抽血，测定白细胞计数和血浆L-选择素、白细胞介紊（IL）-6、IL-8、髓过氧化物酶（MPO）水平。于过滤后30、60、90min时测定滤器内IL-6、IL-8浓度，并在过滤后90min时取滤膜行病理学检查。结果LD组T1时白细胞计数低于C组；两组CPB期间血浆L-选择素、IL-6、IL-8浓度均高于T0，T5时LD组血浆L-选择素、IL-6、IL-8、MPO水平均低于C组。过滤后60、90min时滤器中IL-6、IL-8浓度高过滤后30min；滤器内白细胞滤膜全层布满白细胞，人血面白细胞多于出血面。结论白细胞滤除能抑制犬CPB所引起的全身炎性反应。     

The systemic inflammatory response syndrome

Sepsis and septic shock are the leading causes of death in intensive care units in developed countries despite recent advances in critical care medicine. Sepsis is the systemic inflammatory response to infection frequently associated with hypoperfusion followed by tissue injury and organ failure. The activation of monocytes/macrophages and neutrophils, with the consecutive release of pro-inflammatory mediators and activation of the coagulation cascade, seems to play a key role in the pathogenesis of sepsis. Elimination of the septic focus, anti-microbial therapy and supportive treatment are the cornerstones of sepsis therapy. In addition, the application of small doses hydrocortisone to patients with refractory septic shock and the treatment of patients with septic multiple organ failure with activated protein C are two adjunctive therapeutic strategies. Promising new experimental treatment options are interference with MIF, HMGB1, C5a or TREM-1 signal transduction pathways and an inhibition of apoptosis, which may further improve the prognosis of septic patients in the future.