抑肽酶对长期低温保存兔肺的保护作用的研究

目的 :探讨抑肽酶对长期低温保存兔肺保护作用。方法 :应用离体兔肺缺血再灌注模型 ,15只白兔随机分为三组 (抑肽酶组、对照组 1、对照组 2 ) ,抑肽酶组和对照组 1用Euro -Collins液进行肺灌洗和低温保存(10℃ ,2 4h)后 ,以新鲜兔血离体灌注 30min。抑肽酶组在兔血中加入抑肽酶 (2 5万KIU) ;对照组 1不用抑肽酶。对照组 2取自正常兔肺 ,不进行肺灌洗和保存。灌注中测定肺动脉氧差 (△PO2 ) ,肺动脉压 (PAP) ,灌注完毕取肺电镜观察微观结构。应用TUNEL(末端脱氧核糖核酸转移酶 (TdT)介导的dUTP缺口末端标记 )技术检测肺细胞凋亡情况。结果 :与对照组 1比较 ,抑肽酶组的动静脉氧差较大 (2 0min时差异显著 ,P <0 .0 5 ) ,肺动脉压较低 (P <0 .0 5 )。电镜观察对照组 1肺结构破坏重。细胞凋亡检测显示对照组 1细胞凋亡数目高于抑肽酶组 (P =0 .0 0 18)和对照组 2 (P =0 .0 0 0 1) ,抑肽酶组细胞凋亡数目高于对照组 2 (P =0 .0 0 0 )。结论 :抑肽酶对于长期低温保存的兔肺有保护作用。细胞凋亡可作为评价肺移植后保护效果的指标之一。     

Effects of aprotinin on endothelium-dependent relaxation of large coronary arteries

Objective: Aprotinin is widely used in heart surgery for reduction of intraoperative blood loss. But recent reports presenting results from rat aorta experiments claimed that aprotinin selectively impairs endothelium-dependent relaxation (EDR) as well as basal NO availability in concentrations similar to doses routinely used in cardiovascular surgery. An impairment of coronary EDR by aprotinin would be a great danger for any cardiothoracic intervention. We therefore tested the influence of aprotinin in the coronary arteries of a non-rodent species. Methods: Fresh coronary arteries of pigs were obtained from the local slaughterhouse and transported to our laboratory in cold oxygenated Krebs–Henseleit solution. Five-millimeter long rings were consecutively tested with or without aprotinin in concentrations of 500 KIU/ml (n = 7) or 1000 KIU/ml (n = 6) in oxygenated normothermic Krebs–Henseleit solution. PGF₂ (10 μmol/l) was used for inducing contraction and substance P (10 nmol/l) for inducing EDR, which was calculated in percentage of the precontraction. Indomethacin (10 μmol/l) was added in all measurements to eliminate the influence of prostaglandins. In additional similar experiments (n = 5), the influence of 1000 KIU/ml aprotinin on the EDR caused by the endothelium-derived hyperpolarizing factor (EDHF) was tested using l-NNA (300 μmol/l) to block all NO formation. Results: The EDR of pig coronaries (82 ± 5% or 80 ± 5% of the precontraction in the control tests before and after aprotinin exposure) was not significantly changed by 500 KIU/ml aprotinin (78 ± 7%). A small, but significant reduction of less than 1/10 of the EDR was induced by 1000 KIU/ml aprotinin (74 ± 5%). After accounting for l-NNA for NO blockage, no aprotinin-related difference remained (59 ± 6% vs 60 ± 6% in controls). Conclusion: For clinically relevant concentrations of aprotinin up to 500 KIU/ml, no significant reduction of the EDR can be found in epicardial coronary arteries of the pig. For higher doses of 1000 KIU/ml, a reduction in NO production seems to be the cause of the small but significant reduction of the EDR by aprotinin. Therefore, danger for impairment of coronary EDR by aprotinin at clinical dosage levels, as suggested by studies on rat aortas, seems to be absent in coronary arteries of a large mammalian model.     

Bioavailability of 1-deamino-8-D-arginine vasopressin with an enzyme inhibitor (aprotinin) from the small intestine in healthy volunteers

Objective: The bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP), with and without an enzyme inhibitor, was studied in six healthy, male volunteers aged 19–34 years, followed for 8 h after each drug administration. Methods: For i.v. administration the subjects received 4 μg dDAVP. For intestinal administration 500 μg dDAVP was administered directly, in two separate sessions, in the first part of the duodenum via a triple-lumen channel tube. In one session a solution of isotonic polyethylene glycol (PEG) was given as a continuous enteral perfusion. In the other session a solution of PEG and aprotinin was administered enterally at the constant rate of 5 ml⋅min⁻¹ for 4 h. Plasma dDAVP was measured using a specific, sensitive radioimmunoassay and intestinal juice was collected for measurement of lipase, chymotrypsin and pH every 30 min for 5 h. Results: The intestinal chymotrypsin activity was decreased after perfusion of aprotinin while the lipase activity was not modified. After i.v. administration, the half-life of elimination of dDAVP was 1.56 h and plasma clearance 1.24 ml⋅min⋅kg⁻¹. The mean bioavailability after duodenal administration of dDAVP + aprotinin was 0.46% compared with 0.09% after duodenal administration of dDAVP alone. The bioavailability of dDAVP after direct duodenal administration of an aqueous solution was similar to that after swallowing a tablet in a previous study and increased 5 times when given together with a perfusion of an enzyme inhibitor. Received: 27 October 1995/Accepted in revised form: 26 February 1996     

45. Die Schocklunge - ein neues Behandlungsprinzip

Zusammenfassung In einer retrospektiven Studie werden an 2 Kollektiven von je 38 und 60 Patienten mit Pneumonitis (Schocklunge) zwei Behandlungsmethoden verglichen. Die erste Gruppe erhielt Heparin in Kombination mit Aprotinin. Im zweiten Kollektiv gaben wir Heparin, Frischplasma, Nicotinsäure, Methylprednisolon und alpha-Receptor-Blocker. In dem ersten Kollektiv betrug die Gesamtletalität 50%. Von den beatmeten Patienten verstarben 64%. Im zweiten Kollektiv betrug die Gesamtletalität 26,5%. Von den beatmeten Patienten verstarben 33%. Auf Grund unserer Erfolge halten wir zum jetzigen Zeitpunkt eine Kombinationstherapie mit Aprotonin für nicht mehr indiziert.     

抑肽酶对成年豚鼠心肌再灌注损伤的保护作用

目的：探索抑肽酶的心肌保护作用。方法：建立离体心脏顺行灌注后左心做功模型，２０只成年豚鼠随机分为Ａ、Ｂ两组，分别以４℃Ｓｔ．ＴｈｏｍａｓＨｏｓｐｉｔａｌｃａｒｄｉｏｐｌｅｇｉｃｓｏｌｕｔｉｏｎＮｏ．２（ＳＴＳ）和ＳＴＳ＋抑肽酶（１５０ＫＩｕｍＬＳＴＳ）为心停搏液，测定缺血（９０分钟，２０℃）前、后和再灌注（６０分钟）时心脏动力学指标，心肌腺苷酸和丙二醛含量，并行心肌电镜观察。结果：Ｂ组再灌注后的心功能恢复，腺苷酸贮备和超微结构的改善明显高于或优于Ａ组，而丙二醛含量显著低于Ａ组（Ｐ＜０．０５）。结论：抑肽酶加入ＳＴＳ中可减少氧自由基产生，对成年豚鼠心肌缺血再灌注损伤有保护作用。     

Identification of a novel pulmonary oedema producing toxin from Indian red scorpion (Mesobuthus tamulus) venom.

The experiments were conducted to identify the toxin that produces pulmonary oedema in Mesobuthus tamulus (BT) envenomed animals. Crude BT venom was subjected to Sephadex gel filtration (G-75) and the fractions were screened for optical density (OD), neurotoxicity (prolongation of compound action potential in frog sciatic nerve) and lethality. All these parameters exhibited a peak between 54-94 ml eluates. Fractions of this peak were pooled (SP) and loaded on to carboxymethyl cellulose column. The column was then eluted with increasing buffer concentrations at constant pH and temperature. Eluates were screened for neurotoxicity and OD. Four peaks of neurotoxic activity (T1-T4) were detected. T2 and T3 were lethal whereas T1 and T4 were non-lethal. T2 exhibited mainly neurotoxicity and failed to augment phenyldiguanide (PDG)-induced reflex response or to produce pulmonary oedema. T3 was having minimal neurotoxic actions but augmented PDG-reflex and produced pulmonary oedema. The effects of T3 persisted even after dialysis with 8 kDa cut-off filter but not those of T2. The T3 effects resembled toxic manifestations of BT venom and were blocked by aprotinin pre-treatment. T3 demonstrated a band at approximately 100 kDa in SDS-PAGE. The results demonstrate the presence of a lethal, high molecular weight, pulmonary oedema producing toxin in BT venom.     

抑肽酶用于减少脊柱矫形手术出血的观察

目的探讨在脊柱矫形手术应用大剂量抑肽酶减少出血量的疗效。方法对30例应用抑肽酶的脊柱矫形手术的出血量与对照组的资料进行临床分析。结果用药组比对照组的出血量显著减少。结论术前应用大剂量抑肽酶可显著减少脊柱矫形手术的出血量。     

乌司他丁对婴幼儿体外循环心脏手术血小板功能的保护作用

目的 探讨乌司他丁在婴幼儿心肺转流(CPB)围术期对血小板功能的保护及止血作用.方法 45例3岁以下房间隔缺损(ASD)或室间隔缺损(VSD)患儿随机分为三组,每组15例,分别在预充液中一次性加入抑肽酶(A组)、乌司他丁(U组)或未用药(C)组;选取4个时间点采静脉血测定血小板膜糖蛋白受体GP Ⅰ b和GPⅡb/Ⅲ a及血小板计数;记录术后纵隔引流量及输血量.结果 GP Ⅰ b、GP Ⅱ b/Ⅲa组内及A、U组与C组之间比较有统计学意义(P<0.01),A组与U组间无统计学意义.血小板计数组间比较无统计学意义.A、U组术后纵隔引流量明显少于C组(P<0.05),U组与A组间无统计学意义.三组术后输血量无统计学意义.结论 乌司他丁在婴幼儿先心病围术期通过保护GP而对血小板功能有部分保护作用,从而减轻术后非外科性出血,减少输血量,可取代抑肽酶作为婴幼儿先心病手术的血液保护用药.     

乌司他丁和抑肽酶对心肌缺血再灌注损伤保护作用的对比研究

目的评价乌司他丁和抑肽酶对小儿心内直视术围体外循环(CPB)期心肌缺血再灌注损伤的保护作用。方法按入选标准筛选2004-01—2005-08在温州医学院附属第二医院治疗的90例先天性心脏病患儿,随机双盲法分成6组:对照组(A组),小剂量乌司他丁组(10000U/kg,B组),大剂量乌司他丁组(20000U/kg,C组),小剂量抑肽酶组(75000kIU/kg,D组),大剂量抑肽酶组(150000kIU/kg,E组),小剂量乌司他丁 小剂量抑肽酶组(F组),每组15例。于CPB前(T1)、升主动脉开放后5min(T2)、CPB结束后30min(T3)、4h(T4)、24h(T5)5个时间点抽取桡动脉血,行血浆心肌肌钙蛋白I(cTnI)浓度及肌酸磷酸激酶(CK)、肌酸磷酸激酶同工酶(CK-MB)活性测定。术中定时监测激活全血凝固时间(ACT),红细胞压积(HCT);同时记录主动脉阻断(ACC)时间、总转流时间、心脏复跳情况及围术期血管活性药物使用情况。结果C、E、F组cTnI、CK、CK-MB明显低于A组(P<0.05);在T5点,B、D组cTnI明显低于A组(P<0.05)。与F组比较,A、B、D组cTnI、CK-MB,A组CK浓度明显升高(P<0.05)。B组与C组、D组与E组比较,cTnI、CK-MB浓度明显升高(P<0.05)。F组自动复跳率较A组增高,血管活性药物使用率较A组降低(P<0.05)。结论围CPB期单次使用乌司他丁和抑肽酶都能减轻心肌缺血再灌注损伤,药效呈剂量依赖性,但两者的保护作用差异无显著性;使用小剂量乌司他丁加小剂量抑肽酶减轻心肌损伤较为合理。     

抑肽酶联合控制性降压在脊柱手术中的应用

目的 探讨抑肽酶联合控制性降压在脊柱手术中应用的血液保护效应.方法 45例择期行脊柱手术患者,随机均分为抑肽酶联合控制性降压组(联合组)、单纯控制性降压组(降压组)和对照组.分别在术前、术毕、术后24 h抽血检测血常规和凝血功能.比较三组患者手术失血量、输血量和凝血功能变化.结果 联合组与降压组手术失血量、输血量、术后24 h切口引流量均较对照组明显下降(P<0.01),联合组上述指标低于降压组(P<0.05).与对照组和降压组比较,联合组术后部分凝血活酶时间(APTT)延长(P<0.01),纤维蛋白原(Fib)值偏高(P<0.05).结论 抑肽酶联合控制性降压可明显减少脊柱手术的失血量和异体血的输入量.