Prehospital Thrombolysis: A Manual from Berlin

In acute ischemic stroke, time from symptom onset to intervention is a decisive prognostic factor. In order to reduce this time, prehospital thrombolysis at the emergency site would be preferable. However, apart from neurological expertise and laboratory investigations a computed tomography (CT) scan is necessary to exclude hemorrhagic stroke prior to thrombolysis. Therefore, a specialized ambulance equipped with a CT scanner and point-of-care laboratory was designed and constructed. Further, a new stroke identifying interview algorithm was developed and implemented in the Berlin emergency medical services. Since February 2011 the identification of suspected stroke in the dispatch center of the Berlin Fire Brigade prompts the deployment of this ambulance, a stroke emergency mobile (STEMO). On arrival, a neurologist, experienced in stroke care and with additional training in emergency medicine, takes a neurological examination. If stroke is suspected a CT scan excludes intracranial hemorrhage. The CT-scans are telemetrically transmitted to the neuroradiologist on-call. If coagulation status of the patient is normal and patient''s medical history reveals no contraindication, prehospital thrombolysis is applied according to current guidelines (intravenous recombinant tissue plasminogen activator, iv rtPA, alteplase, Actilyse).Thereafter patients are transported to the nearest hospital with a certified stroke unit for further treatment and assessment of strokeaetiology. After a pilot-phase, weeks were randomized into blocks either with or without STEMO care. Primary end-point of this study is time from alarm to the initiation of thrombolysis. We hypothesized that alarm-to-treatment time can be reduced by at least 20 min compared to regular care.     

Recombinant Destabilase from Hirudo medicinalis Is Able to Dissolve Human Blood Clots In Vitro

Leeches are amazing animals that can be classified as conditionally poisonous animals since the salivary cocktail they produce is injected directly into the victim, and its components have strictly defined biological purposes, such as preventing blood clot formation. Thrombolytic drugs are mainly aimed at treating newly formed blood clots. Aged clots are stabilized by a large number of isopeptide bonds that prevent the action of thrombolytics. These bonds are destroyed by destabilase, an enzyme of the leech’s salivary glands. Here, we conducted a pilot study to evaluate the feasibility and effectiveness of the use of destabilase in relation to blood clots formed during real pathological processes. We evaluated the isopeptidase activity of destabilase during the formation of a stabilized fibrin clot. We showed that destabilase does not affect the internal and external coagulation cascades. We calculated the dose–response curve and tested the ability of destabilase to destroy isopeptide bonds in natural blood clots. The effect of aged and fresh clots dissolving ability after treatment with destabilase coincided with the morphological characteristics of clots during surgery. Thus, recombinant destabilase can be considered as a potential drug for the treatment of aged clots, which are difficult to treat with known thrombolytics.     

Rt-PA静脉溶栓治疗急性脑梗死的疗效及对血清IL-6，IL-17及VEGF水平的影响

目的:探讨重组组织纤溶酶原激活剂(Rt-PA)静脉溶栓治疗急性脑梗死的疗效及对血清白介素-6(IL-6)、IL-17及血管内皮生长因子(VEGF)水平的影响。方法:选择2014年8月至2016年8月我院接诊的86例急性脑梗死患者,通过随机数表法分为观察组(n=43)和对照组(n=43)。对照组给予常规治疗,观察组在对照组基础上进行Rt-PA静脉溶栓。比较两组的治疗效果、不良反应的发生情况、治疗前后美国国立卫生研究院卒中量表(NIHSS)评分、Barthel指数、血清IL-6、IL-17及VEGF水平的变化。结果:治疗14 d后,观察组NIHSS评分显著低于对照组,Barthel指数明显高于对照组(P0.05);观察组在治疗后1 d、3 d、7 d、14 d时血清IL-6、IL-17水平均显著低于对照组(P0.05),治疗后1 d、3 d、7 d时血清VEGF水平明显高于对照组,治疗后14 d时血清VEGF水平显著低于对照组(P0.05)。观察组治疗后总有效率显著高于对照组(P0.05)。结论:在急性脑梗死患者中早期采用Rt-PA治疗的效果显著,可有效促进神经功能恢复,且安全性高,可能与其降低血清IL-6、IL-17、VEGF水平有关。     

血栓溶解酶产生菌及其培养条件的研究

通过对根霉１２号发酵液的分析及发酵条件的研究,发现其发酵液中含有能溶解血栓的物质,但不能分解血细胞。它在麸皮胰蛋白胨培养基（ｐＨ５．１）上３０℃振荡培养４８～６０ｈ,ｐＨ值达到７．４左右时产生血栓溶解酶的活力最高。     

重组葡激酶对小型猪冠脉血栓的溶栓作用研究*

目的: 评价重组葡激酶的溶栓效力,并与相同作用方式的重组链激酶进行比较。方法: 30只中国实验小型猪分成5组,分别为溶剂对照组、阳性药对照组和三个重组葡激酶组,每组6只,采用麻醉动物、手术开胸、直流电刺激形成冠脉血栓;在冠脉血栓形成30 min后开始静脉给药,采用先推注、再蠕动泵恒速输注的方式给药;溶剂对照组静脉推注对照液,阳性药对照组静脉给予重组链激酶4 mg·kg^-1,三个重组葡激酶组分别静脉给予4 mg·kg^-1、2 mg·kg^-1、1 mg·kg^-1重组葡激酶,静脉推注体积为5 ml,1 min内注毕,输注速度为0.5 ml·min^-1,60 min内输毕,120 min后放血处死动物。于给药前及给药后30、60、120 min取静脉血,实验结束后取血栓形成部位的冠脉血管段,分别检测优球蛋白溶解时间(ELT)、血纤维蛋白原含量(Fbg)、纤维蛋白(原)降解产物(FDP)和伤口出血量,检测冠脉血栓溶解率、心肌缺血程度及缺血范围。结果: 与溶剂对照组相比,试验组ELT明显缩短(P＜0.05或P＜0.01),FDP 明显升高(P＜0.05或P＜0.01),较少量实验动物Fbg降解超过20%,对小型猪血压及心率无明显影响。与对照组相比,试验组高、中2个剂量组,最大血栓面积分别减少34.3%、15.4%(P＜0.05)。与等剂量的重组链激酶相比,重组葡激酶对电刺激引起的冠脉血栓具有更强的溶栓作用(P＜0.05或P＜0.01),引起的出血副反应少。结论: 重组葡激酶对小型猪冠脉血栓有较好的溶栓作用,相比重组链激酶,溶栓速度快、具有更高的纤维蛋白专一性,出血副反应较少。综合比较, 2 mg·kg^-1重组葡激酶具有较好的临床疗效和安全性保障。     

蚓激酶研究进展

蚓激酶是一种新型的溶栓制剂,具有良好的溶血栓治疗效果。综述了至今为止分离到的蚓激酶成分、生物学活性、药物学作用、抑制剂和空间结构分析等方面的研究进展 。     

Neuroprotection and stroke: time for a compromise

In April 2007, there existed a repertory of 286 trials concerned with acute ischemic stroke on the Stroke Trials Registry ( http://www.strokecenter.org/trials/ ), of which 209 trials were considered as complete (with no evidence of patient benefit unless one considers the much hard fought for and modest results of the tPA studies). Among other questions arising from such failures, one can wonder whether the plethora of pharmacological agents that exhibited neuroprotective properties in pre-clinical studies were selected for clinical trials entirely based upon their experimental efficacy. This mini-review will try to point out some of the weaknesses that could underline the failure of both researchers and clinicians involved in the field of stroke to obtain their ultimate goal – brain protection.     

间歇性充气加压疗法对下肢深静脉血栓患者血液流变学的影响

目的:观察间歇性充气加压疗法(intermittent pneumatic compression,IPC)对下肢深静脉血栓形成(deep vein thrombosis of lower limbs,DVT)患者的治疗效果,并从血液流变学方面探讨间歇性充气加压的作用机理.方法:2003年3月-2010年9月我科收治的243例下肢深静脉血栓患者,将其中42例IPC治疗病例定为B组实验组,145例单纯药物治疗病例中选取60例定为A组对照组.观察两组患者血液流变学指标和小腿肿胀消退情况的对比.结果:两组患者全血粘度、红细胞聚集指数、红细胞电泳时间、红细胞变形性,在治疗第1天较入院时无差异,组间无差异(P＞0.05),第3天较入院时有差异(P＜0.05),组间第3天有差异(P＜0.05),两组患者下肢肿胀度均明显消退,但B组肿胀消退速度明显快于对照组(P＜0.05).结论:间歇性充气加压治疗仪可有效改变血液流变学状态,改善血液高凝状态,有效缓解肢体肿胀症状,缩短住院时间.且不增加治疗难度,使用简单,治疗依从性好.     

降纤酶与尼莫地平治疗脑梗死的疗效比较

目的 观察纤纤酶对急性脑梗死患者血浆纤维蛋白原的变化,探讨溶栓与一般离梗死的临床效果。方法 治疗组静脉滴注降纤酶,对组一胸脉滴注尼莫地平。两组分别于用药前,治疗第1天、第7天、第14天测定纤维蛋白原、凝血酶原时间、肝肾功能、神经功能缺损评分及头颅CT。治疗14天进行疗效评定。结果 治疗组治疗前后比较血浆纤维蛋白原明显降低,对照组无明显变化,两组治疗前后比较凝血酶原时间均延长,组临床疗效明显优于对照组（P＜0.025）。结论 降纤酶对血浆纤维蛋白原有明显降低作用,可起到直接溶解和预防血栓形成,是治疗和预防脑梗死的有效药物。     

A prourokinase-RGDS chimera——Construction, expression and characterization

A tetrapeptide, RGDS, was inserted into proUK kringle domain G118-L119 by the construction of a mutant proUK-RGDS gene. The gene was expressed in the baculovirus expression system. Immunoaffinity chromatography was used to purify the chimera and protein with purity over 90% was achieved. The chimera was tested for its platelet membrane binding function and showed a calcium-dependent platelet binding activity. Amidolytic activity of the chimera was tested. The result indicated that specific amidolytic activity of plasmin activated chimera was 62000 IU/mg, comparable to the previously reported 65 355 IU/mg of plasmin activated natural proUK. Activation of plasminogen by the chimera after plasmin treatment followed Micbieal-Menten kinetics, and the Km was 0.97 μmol/L, which was also comparable to 1.64 μmol/L of native urokinase. The chimera also showed intensive ability to inhibit platelet aggregation in vitro. These results indicate that this chimera might be useful as a bifunctional thrombolytic agent.