抑肽酶在体外循环中的应用

抑肽酶为丝氨酸蛋白酶抑制剂,在体外循环心内直视手术中大剂量应用可显著减少术后失血量及输血量,目前抑肽酶在体外循环中的用法、用量尚未统一,作用机制也未完全阐明,但对它的临床效果已基本肯定,且未发现明显毒、副作用,在心内直视手术中的应用已越来越广泛。     

体外循环中肝素、鱼精蛋白对血小板的激活及抑肽酶的抑制作用

目的研究在体外循环中肝素化及鱼精蛋白中和时血小板的激活以及应用抑肽酶对这种激活的抑制作用。方法２０例心脏瓣膜置换术患者随机等分为两组：对照组和抑肽酶组，分别于肝素化及应用鱼精蛋白前后检测血小板胞浆游离钙浓度，磷脂酶Ａ２活性及血浆血栓素水平。结果上述指标在肝素化及鱼精蛋白中和后均显著升高，其中鱼精蛋白中和时升高幅度更大，应用抑肽酶对肝素及鱼精蛋白所引起的上述改变均有显著抑制作用。结论抑肽酶对肝素和鱼精蛋白所致的血小板激活有显著抑制作用，这可能与抑肽酶在体外循环中的止血作用有关。     

抑肽酶对体外循环中血小板花生四烯酸代谢的保护

选择４５例心脏瓣膜置换术患者，其中２３例应用小剂量抑肽酶作用为药组观察体外循 期间血小板的功能失调与花生四烯酸代谢紊乱，以及小剂旺抑肽酶的防治效果。结果发现；用药组术后失血量比对照组减少了５０．２％，输血旺减少６７．０％．对照组ＣＰＢ期间血小板胞浆游离钙浓度及膜磷脂酶Ａ２，环氧化酶活性，血浆ＴＸＡ２水平及ＴＸＡ２／ＰＧＩ２比均显著升高，用药组上述改变的均受到显著抑制。     

体外循环中小剂量抑肽酶对血栓素及血小板功能与结构的作用

体外循环中小剂量抑肽酶对血栓素及血小板功能与结构的作用李建华＊孙继领＊高小环＊王京庆＊王红卫＊表１两组血小板计数聚集功能粘附功能ＴＸＢ２ＰＧＦ１α及ＴＸＡ２／ＰＧＦ１α变化（ｘ±ｓ）组别麻醉后ＣＰＢ１０ｍｉｎＣＢＰ４０ｍｉｎ术终术后２ｈ术后１２ｈ术后...     

小剂量抑肽酶在体外循环中对血小板功能的保护作用

本文取３０例患者，随机分为两组（每组１５例），对照组预充液中加入等量的生理盐水；实验组预充液中一次性加入１５～２０×１０６ＫＩＵ抑肽酶。观察两组转机前后血小板计数和平均体积及血小板粘附、聚集功能。结果为转机后血小板数量变化不大，对照组的血小板功能较实验组明显下降。实验组的出血量及输血量较对照组低，表明小剂量抑肽酶能够保护转机期间血小板功能，减少术后出血。     

抑肽酶对体外循环中血小板膜糖蛋白的影响

本研究拟利用流式细胞技术观察体外循环中抑肽酶对血小板膜糖蛋白Ⅱb、Ⅲa(GPⅡb、Ⅲa)表达的影响,以探讨抑肽酶作用的分子生物学机制。资料及方法选择30例先天性房缺或/并室缺患儿,年龄在3～15岁,体重12～28 kg,心功能Ⅰ～Ⅱ级,男14例,女16例,随机分为两组:对照组和抑肽酶组。术前用药均为肌注哌替啶1mg/kg、氟哌利多0.1 mg/kg、东莨菪碱0.01 mg/kg,入室后静脉     

在体外抑肽酶对血小板的作用

选择健康献血员取血，观察抑肽酶在体外对血小板功能及花生四烯酸代谢的影响，抑肽酶剂量分为三组：５０ＫＩＵ／ｍｌ（对照组）、１５０ＫＩＵ／ｍｌ（小剂量组）、３００ＫＩＵ／ｍｌ（大剂量组）。结果表明：抑肽酶可显著抑制血小板粘附率以及由ＡＤＰ和凝血酶所诱导的血小板聚集，这两种抑制均为可复性，大剂量与小剂量无明显差异。抑肽酶对ＡＤＰ所诱导的磷脂酶Ａ２，环氧化酶的活化具有显著抑制作用，但当它们已被激活时并不能     

抑肽酶在体外循环术中的应用

１０１例各种心脏直视手术病例在体外循环中应用抑肽酶，另以同期５２例心脏直视手术病例作为对照，研究大剂量抑肽酶在心脏直视手术中的作用，用药组转流结束后创面较对照组干燥，手术止血时间缩短，术中失血减少，术后２４小时出血量减少约５０％（用药组３１６±１１４ｍｌ，对照组５９８±１９７ｍｌ）；库血输入量抑肽酶组亦比对照组用量少（用药组４６８±１４８ｍｌ，对照组７８３±１２２ｍｌ）。大剂量抑肽酶在体外循环中的应用是安全有效的，它明显减少术中、术后的出血及库血用量。     

小剂量抑肽酶在体外循环中保护血小板作用及减少术后出血

为评估小剂量抑肽酶（１．５×１０６ＫＩＵ）对血小板功能的保护及止血作用，用药组（Ａ组ｎ＝２０）体外循环（ＣＰＢ）预充液中一次性加抑肽酶，对照组（Ｂ组ｎ＝２０）加入同容积生理盐水。检测结果Ａ组较Ｂ组血小板计数、血小板聚集率均增高；血栓烷Ｂ２下降；ＡＣＴ延长但中和效果佳；术中止血时间缩短；术后失血量和输血量明显降低。结论：小剂量抑肽酶减轻血小板膜受体在ＣＰＢ中的损害、增强其聚集功能、减轻血小板数量下降；抑肽酶与肝素有协同作用并竞争性抑制肝素对血小板功能抑制；明显减少手术后失血和输血量。     

体外循环对血小板功能影响的研究

选择心脏瓣膜替换术病人１０例，用流式细胞术（ＦＣＭ）方法在围术期定量检测血小板质膜蛋白Ｉｂ、ＩＩｂ／ＩＩａ复合物、血小板α颗粒膜蛋白、溶酶体完整膜蛋白－ＣＤ６３及血小板计数等项血小板膜糖蛋白指标进行统计学处理。结果表明体外循环中血小板计数、膜糖蛋白Ｉｂ均明显下降；α－颗粒膜蛋白１４０、溶酶体完整膜蛋白及膜糖蛋白Ｉｂ／ＩＩａ均显著增高。证实体外循环（ＣＰＢ）对血小板膜糖蛋白的影响，更深入了解ＣＰＢ导致血小板功能获得性损害的分子机制。     

氨甲苯酸和抑肽酶对体外循环中肝素抗凝作用的影响

目的为探讨氨甲苯酸和抑肽酶的止血疗效。方法将３４例成人心脏手术患者分为３组，Ａ组于体外循环（ＣＰＢ）前、中、后给予氨甲苯酸共７５０ｍｇ；Ｂ组ＣＰＢ中给予抑肽酶２００万Ｕ；并设一对照组。结果氨甲苯酸使ＣＰＢ中激活全血凝固时间（ＡＣＴ）明显缩短，追加肝素量较另两组显著增加（Ｐ＜０．０５），２４小时胸液量较对照组减少２３％（Ｐ＞０．０５）。抑肽酶使ＣＰＢ中ＡＣＴ略延长，与对照组相比无统计学意义，对肝素用量无影响，２４小时胸液减少３５％（Ｐ＜０．０５）。两用药组术中术后库血用量均显著减少（Ｐ＜０．０１），术后胸液量相似（Ｐ＞０．０５）。结论氨甲苯酸止血疗效弱并缩短ＡＣＴ及明显增加肝素用量，不如抑肽酶疗效可靠。     

大剂量抑肽酶对体外循环导致凝血机制紊乱的作用

３０例行心脏直视手术病人随机分为对照组和抑肽酶用药组。于麻醉后、主动脉阻断开放时、体外循环结束后１０ｍｉｎ、２ｈ和术后２４ｈ，分别观察血小板计数、血小板聚集率、ＴＸＢ２、６－ｋｅｔｏ－ＰＧＦ１α、ⅧＲ：Ａｇ、ＡＴⅢ：Ａ与ＦＤＰ，并记录术后２４ｈ纵隔心包引流量。结果表明，大剂量抑肽酶可增加术后血小板功能、抑制纤溶、提高术后凝血因子含量等，从而减少了术后出血。     

Changes in Platelet, Granulocyte, and Complement Activation During Cardiopulmonary Bypass Using Heparin-coated Equipment

Abstract: The effects of heparin-coated cardiopulmonary bypass (CPB) systems on platelet, granulocyte, and complement activation were investigated during cardiopulmonary bypass. Thirty patients underwent coronary artery bypass surgery with a heparin-coated (Carmeda Bio-Active Surface, CBAS, Medtronic, U.S.A.) CPB system (HC group, n = 10), a heparin-coated oxygenator and uncoated CPB circuit (HO group, n = 10), or an uncoated system (UC group, n = 10). In the HO group, plasma C3a (1667 ± 632 ng/ml) and C4a (1088 ± 319 ng/ml) concentrations were significantly (p < 0.05) lower than in the UC group (2846 ± 1045 ng/ml and 1494 ± 480 ng/ml, respectively) 10 min after the administration of protamine, but there were no significant differences in the platelet or granulocyte counts. In the HC group, granulocyte elastase concentrations 120 min after the onset of CPB (365 ± 177 μg/L) and 10 min after the administration of protamine (676 ± 314 μg/L) were significantly (p < 0.05) lower than in the other 2 groups (820 ± 341 and 893 ± 303 μg/L and 1365 ± 595 and 1,258 ± 622 μg/L). In addition, the increase in the plasma C3a concentration in the HC group 60 (p < 0.05) and 120 min after the onset of CPB (p < 0.05) was significantly less than in the other 2 groups. The C3a and C4a concentrations 10 min after the administration of protamine were significantly (p < 0.005 and p < 0.05) less in the HC group than in the UC group. Platelet counts 10 min after the administration of protamine were significantly higher (p < 0.05) and plasma β-throm-boglobulin concentrations during CPB were significantly lower in the HC group than in the other 2 groups 5 (p < 0.05), 60, and 120 min (p < 0.005) after the onset of CPB. Postoperative blood loss during the first 12 h in the HC group was significantly (p < 0.05) less than that in the UC group. The heparin-coated oxygenator and uncoated CPB circuit reduced complement activation but demonstrated no significant effects on the platelet and granulocyte systems. However, the heparin-coated CPB circuit (with all components making blood contact) reduced platelet, granulocyte, and complement activation and significantly reduced postoperative blood loss. Therefore, heparin coating of CPB systems improves biocompatibility.     

体外循环时小剂量抑肽酶对纤溶系统和血小板的影响

心脏直视手术体外循环时应用小剂量抑肽酶，观察其对纤溶系统和血小板的影响。３０例随机分为对照组和抑肽酶用药组。用药组仅一次在预充液中加入小剂量抑肽酶２×１０６ＫＩＵ。分别于转流前、转流３０分钟、转流结束时及转流停止后２小时测定ＰＬＧ、ＦＤＰ、ＰＫ、ＴＸＢ２、ｔ－ＰＡ、６－ｋｅｔｏ－ＰＧＦ１α，ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α浓度。术后２４小时纵隔心包引流量用药组较对照组减少出血４１．７％，Ｐ＜０．０１。电镜观察用药组血小板改变不明显；对照组呈现破碎、脱颗粒、微管扩张、聚集。作者认为小剂量抑肽酶能有效地抑制高纤溶活性，可保护血小板功能，减少术后出血。     

Aprotinin Reduces the Expression of P-Selectin on the Surface of Platelet and Leukocyte-Platelet Conjugates

P-Selectin, an adhesion molecule expressed on the surfaces of activated platelets and the vascular endothelium, mediates platelet binding to monocytes and neutrophils. Monocytes and neutrophils produce superoxide anion by activated platelets through p-selectin. Aprotinin, a serine protease inhibitor, inhibits plasmin to activate platelets during cardiopulmonary bypass (CPB). A total of 25 patients were studied to clarify the effects of aprotinin on p-selectin expression during CPB. Nine patients were not given aprotinin (control group), and 16 were given aprotinin of 2 million U in the priming solution (aprotinin group). The platelet count and soluble p-selectin in the plasma, p-selectin on the surface membranes of platelets, and leukocyte-platelet conjugate levels were measured during and after CPB. The platelet count was maintained well in the aprotinin group. The increases of soluble p-selectin in the plasma, platelet surface p-selectin, and leukocyte-platelet conjugates were less in the aprotinin group than in the control group (p < 0.05). In conclusion, aprotinin in patients undergoing CPB may reduce the early inflammatory reactions induced by p-selectin.