国产抑肽酶的临床应用

心脏外科手术中，体外循环转流能破坏血小板及凝血系统的功能。近年来有研究表明，抑肽酶作为一种蛋白酶抑制剂，有良好的抑制纤溶系统及保护血小板的功能，我们将５８例患者随机分成两组，观察术中和术后血小板功能、输血量和胸腔引流量、ＡＣＴ及尿量。研究表明，抑肽酶对血小板功能具有保护作用，可减少术后出血及库血用量，减少因出血和输血所引发的一系列并发症。本研究未发现应用国产抑肽酶所造成的副作用。     

Efficacy of tranexamic acid as compared to aprotinin in open heart surgery in children

Background:

Coagulopathy is a major issue in children undergoing high-risk pediatric cardiac surgery. Use of anti-fibrinolytics is well documented in adults, but recently there are questions raised about safety and effectiveness of their use on routine use. Tranexamic acid is a potent anti-fibrinolytic, but its role is not fully understood in children. This study aims to study the benefits tranexamic acid in controlling postoperative bleeding in pediatric cardiac surgical patients.

Methods and Results:

Fifty consecutive children who underwent cardiac surgery were randomized prospectively to receive either aprotinin (Group A; n = 24) or tranexamic acid (Group B; n = 26) from September 2009 to February 2010 were studied. Primary end points were early mortality, postoperative drainage, reoperation for bleeding and complications. Mean age and body weight was smaller in Group A (Age: 48.55 vs. 64.73 months; weight 10.75 vs. 14.80 kg) respectively. Group A had more cyanotic heart disease than Group B (87.5% vs. 76.92%). Mean cardiopulmonary bypass time (144.33 vs. 84.34 min) and aortic cross-clamp time (78.5 vs. 41.46 min) were significantly higher in group A. While the blood and products usage was significantly higher in Group A, there was no difference in indexed postoperative drainage in first 4, 8 and 12 h and postoperative coagulation parameters. Mean C-reactive protein was less in Group A than B and renal dysfunction was seen more in Group A (25% vs. 7.6%). Mortality in Group A was 16.66% and 7.6% in Group B.

Conclusion:

Anti-fibrinolytics have a definitive role in high-risk children who undergo open-heart surgery. Tranexamic acid is as equally effective as aprotinin with no additional increase in morbidity or mortality.

Ultramini Abstract:

Coagulopathy has been a major issue in pediatric cardiac surgery, and anti-fibrinolytics have been used fairly regularly in various settings. This study aims to evaluate the efficacy of tranexamic acid as compared against that of aprotinin in a randomized model. Tranexamic acid proves to be equally effective with less toxicity with no added mortality.     

Impact of tranexamic acid vs. aprotinin on blood loss and transfusion requirements after cardiopulmonary bypass: a prospective,randomised, double-blind trial

Summary

Introduction: Aprotinin (AP) reduces blood loss and transfusions after cardiopulmonary bypass (CPB), but may sensitise patients and is expensive. Tranexamic acid (TA) has less side-effects, but data regarding its efficacy are controversial. The aim of our prospective, randomised, double-blind study was to compare the impact of AP vs. TA on drainage blood loss and transfusion requirements in patients undergoing first time CABG on CPB.

Materials and Methods: One hundred and twenty adult patients were randomised to receive either high-dose AP according to Hammersmith or a total of 2 g TA. Perioperative blood products were transfused in a standardised fashion. Blood loss was measured up to 24 h. Demographic and clinical patient data were collected until hospital discharge.

Results: The data from 118 patients (TA: n = 58, TA appears to be a cost-effective alternative to AP AP: n = 60) who completed the study according to protocol were analysed. Blood loss at 24 h postoperation in TA patients was significantly higher (896 ± 354 ml) as compared to AP patients (756 ± 347ml; p = 0.03). TA patients received 1.5 ± 1.5 units of red blood cells (AP: 1.5 ± 1.7, p = 1.0), 1.3 ± 2.0 units of fresh frozen plasma (AP: 1.0 ± 2.0, p = 0.38) and 0.5 ± 1.4 units of platelets (AP: 0.2 ± 0.7, p = 0.15). Clinical data, including perioperative myocardial infarction rate, acute renal failure, mechanical ventilation, hospital stay and mortality, were not significantly different between either group.

Conclusion: Our data show a difference in blood loss between TA and high-dose AP. Although statistically significant, it has little clinical relevance, because perioperative transfusion requirements were similar for both groups. Thus, TA appears to be a cost-effective alternative to AP in primary CABG patients.     

Aprotinin Inhibits Vascular Smooth Muscle Cell Inflammation and Proliferation via Induction of HO-1

Aprotinin is used clinically in cardiopulmonary bypass surgery to reduce transfusion requirements and the inflammatory response. The mechanism of action for the anti-inflammatory effects of aprotinin is still unclear. We examined our hypothesis whether inhibitory effects of aprotinin on cytokine-induced inducible nitric oxide synthase (iNOS) expression (IL-1β plus TNF-α), reactive oxygen species (ROS) generation, and vascular smooth muscle cell (VSMC) proliferation were due to HO-1 induction in rat VSMCs. Aprotinin induced HO-1 protein expression in a dose-dependent manner, which was potentiated during inflammatory condition. Aprotinin reduced cytokine mixture (CM)-induced iNOS expression in a dose dependent manner. Furthermore, aprotinin reduced CM-induced ROS generation, cell proliferation, and phosphorylation of JNK but not of P38 and ERK1/2 kinases. Aprotinin effects were reversed by pre-treatment with the HO-1 inhibitor, tin protoporphyrin IX (SnPPIX). HO-1 is therefore closely involved in inflammatory-stimulated VSMC proliferation through the regulation of ROS generation and JNK phosphorylation. Our results suggest a new molecular basis for aprotinin anti-inflammatory properties.     

体外循环时血小板的构象与功能变化和血液麻醉对其的保护作用

目的 探讨体外循环(CPB)时血小板(PL)的构象与功能变化以及血液麻醉对PL的保护作用.方法 人工血管材料聚对苯二甲酸乙二醇脂(polyethylene terephthalate,PET)表面处理后接枝牛血清白蛋白(BSA)成为PET-BSA.取PET和PET-BSA试片进行对比实验:(1)通过PL乳酸脱氢酶(LDH)的定量测定,计算材料表面吸附的PL量;(2)通过PL的膜糖蛋白GMP140单克隆抗体免疫学测定,计算材料表面活化的PL量;(3)在材料表面进行PL吸附实验,通过扫描电镜观察PL的形态.(4)选择体外循环心内直视手术30例随机分为抑肽酶组和对照组;检测转流中不同时期血液中FDP、PK、PLG和TXB2的量;记录24 h纵隔和心包引流量;电镜观察PL构象.结果 PET-BSA表面吸附的PL量明显低于对照组(P<0.05),活化PL量仅为对照组的20%.扫描电镜显示白蛋白涂层吸附PL少;对照组PL呈重叠状且有伪足.血液麻醉组较对照组纤维蛋白溶解酶原(PLG)分解少,纤溶系统被抑制,PL结构被保护.结论 CPB时血浆蛋白彼此竞争吸附于血管壁上,然后PL与被吸附的血浆蛋白相互作用,PL与构象变化的纤维蛋白在其γ链C端结合位点上结合;同时PL被激活并暴露其CPⅡb/Ⅲa作用位点;构象变化的PL引发凝血的综合进展.抑肽酶的血液麻醉作用是对纤溶酶和激肽释放酶活化的抑制;保护PL结构中的GPⅡb免受破坏,保护了PL术后的凝血功能.     

抑肽酶治疗脑出血脑水肿临床分析

目的:探讨抑肽酶治疗脑出血脑水肿的作用机制。方法:92例高血压脑出血病例随机分为治疗组与对照组。对照组给予20%甘露醇常规减轻脑水肿治疗,治疗组在对照组治疗基础上加用抑肽酶,观察2组疗效和血肿吸收情况。结果:治疗组基本治愈率为77%,明显高于对照组的45%(P<0·05);治疗组各部位血肿全部吸收率为69%,明显优于对照组的45%(P<0·05)。结论:抑肽酶通过对激肽释放酶和激肽级联系统的抑制作用,减少凝血酶的产生和对血肿局部凝血酶的拮抗作用,从而达到促进水肿和血肿吸收作用。     

氨甲环酸与抑肽酶对血液保护功能的对比研究

目的　比较氨甲环酸(TA)与抑肽酶(AP)对体外循环术中血液保护功能的影响,探讨其机制。方法　选取体外循环心脏手术病人 82例,随机分为氨甲环酸用药组、抑肽酶用药组和对照组。TA组总量 1. 5g,于麻醉诱导后切皮前及体外循环开始后两个时间点各给半量,一次性静脉推注;AP组 500万KIU同TA组两个时间点半量分次持续滴注给药,对照组不用药。于术前、后分别测定血小板数量与功能、平均血小板体积、凝血三项、D-二聚体,记录各组术中出血量、术后 12h、24h纵隔心包引流量及术后输血量。结果　AP组与TA组较空白对照组在术前后血小板数量功能变化、D-dimer值及术后引流量、输血量这些方面均有显著性差异 (P<0. 05),而AP组与TA组在此方面的数值差异均无统计学意义。结论　本实验证明了氨甲环酸在体外循环中作用近似抑肽酶,除明显抑制术中体内纤溶系统激活外,在减少术后血小板数目和功能的减低方面发挥了作用。另外两药均可明显减少术后的引流量、全血及成分血的输入量。     

大剂量抑肽酶对体外循环心脏瓣膜置换病人心肌保护作用

目的观察体外循环(CPB)心脏瓣膜置换手术中使用大剂量抑肽酶对心肌的保护作用。方法40例心脏瓣膜置换手术病人,随机分成A组(抑肽组,n=20)和B组(对照组,n=20),A组在体外循环预充液中1次加入5×104kIU/kg抑肽酶;B组在体外循环预充液中加入相等容量的乳酸林格液代替。分别于围术期多时点采取中心静脉血,测定血清心肌肌钙蛋白I(cTnI)、肌酸激酶(CK)及其同工酶(CK-MB)的水平,记录两组转机时间、主动脉阻断时间、开放至复跳时间、自动复跳或电击复跳、复跳后低血压情况。结果A、B两组cTnI在CPB开始后均不同程度升高,A组升高值较B组低,在CPB后各时点的差异显著(P<0·01)。CK、CK-MB明显高于转流前,至开放循环72h后恢复至CPB前水平,A组的变化值均较B组小(P<0·01)。A组心脏自动复跳率、窦性心率恢复率高于B组(P<0·05)。电除颤率、心律失常发生率、复跳后低血压发生率低于B组(P<0·05)。结论体外循环瓣膜置换手术使用大剂量抑肽酶能加强心肌保护的效果,抑肽酶预处理减轻心肌缺血和再灌注造成的损害。     

血凝酶与抑肽酶在人工关节置换术中的应用

目的:评价血凝酶与抑肽酶减少手术出血量的效果及安全性。方法:75例全髋关节置换术患者随机分为Ⅰ、Ⅱ、Ⅲ组,每组25例。术前15min,3组分别静脉注射血凝酶2kU、抑肽酶278IU、注射用水10ml。结果:Ⅰ、Ⅱ组术后24h出血量及术后输血量分别为(286.9±65.6)、(301.9±81.1)ml及(101.8±29.6)、(98.3±36.1)ml,比Ⅲ组的(369.2±59.3)、(220.2±48.5)ml显著减少(P<0.01)。3组术毕血红蛋白、血小板、纤维蛋白原比术前明显降低(P<0.01),但均在正常范围。Ⅱ组有1例发生严重过敏反应。结论:术中应用血凝酶或抑肽酶均有明显的止血效果,但血凝酶更安全。     

抑肽酶对体外循环呼吸指数和胸肺顺应性的影响

目的探讨抑肽酶是否减轻体外循环(CPB)所致急性肺损伤。方法28例首次心脏瓣膜置换术患者随机分为对照组及抑肽酶组，各14例。于CPB前(T1)、主动脉开放后10min(T2)、CPB结束后10min(T3)、60min(T4)监测胸肺顺应性(Cs)和动态肺顺应性(Cd),同步监测吸入气氧浓度(FiO