Zhang B, Wieslander J B
Department of Experimental Research, University of Lund, Malmö University Hospital, Sweden.
Microsurgery. 1996;17(2):89-96. doi: 10.1002/(SICI)1098-2752(1996)17:2<89::AID-MICR3>3.0.CO;2-R.
The study was composed of two parts, arterial and venous; the 24 rabbits in each arm were divided into three equal groups and treated with either saline (control) or 1 mg/kg body weight (bw) of a new recombinant hirudin HBW 023 given as a single dose or standard heparin 1 mg/kg bw followed by quarter doses of heparin every half hour. Both arms included a control group given equal volumes of saline. The study continued for 2 hours. The following parameters were evaluated: bleeding times from arteriotomy/venotomy, patency rates, and the weights of thrombotic materials. Plasma samples were taken for evaluation of anti-factor lla (anti-Flla), anti-factor Xa (anti-Fxa), and activated partial thromboplastin time (APTT). The bleeding times were significantly prolonged but were still within clinically acceptable levels, following both HBW 023 and heparin treatment. Patency rates were significantly improved in both the arterial and venous arms following HBW 023 and heparin treatment. A corresponding reduction in thrombotic materials was simultaneously registered in the arterial and venous arms following HBW 023 and heparin treatment. Hirudin (HBW 023) significantly improved the reduction compared with the heparin group in the venous study. Heparin treatment caused expected high levels of anti-FXa and prolonged APTT, but hirudin, being at least as effective in antithrombotic potency, changed the pre-treatment levels only slightly. Anti-Flla levels were immediately increased by both heparin and hirudin (the highest levels) but reached low levels after 2 hours of single-dose hirudin treatment, despite a simultaneously excellent antithrombotic effect. We conclude that the new recombinant hirudin HBW 023, like standard heparin, is a highly efficient antithrombotic agent in both small arteries and veins following severe vessel wall trauma. The bleeding times were simultaneously prolonged significantly (still within acceptable limits) following both heparin and HBW 023 treatment in the arterial arm but were only prolonged following heparin treatment in the venous arm. The advantage of r-hirudin HBW 023 was furthermore the single dose administration.
该研究由两部分组成，即动脉部分和静脉部分；每个部分的24只兔子被分成三个相等的组，分别用生理盐水（对照组）、1毫克/千克体重的新型重组水蛭素HBW 023单次给药或1毫克/千克体重的标准肝素治疗，随后每半小时给予肝素四分之一剂量。两个部分均包括给予等量生理盐水的对照组。研究持续2小时。评估了以下参数：动脉切开术/静脉切开术后的出血时间、通畅率和血栓物质的重量。采集血浆样本以评估抗凝血因子lla（抗Flla）、抗凝血因子Xa（抗Fxa）和活化部分凝血活酶时间（APTT）。在接受HBW 023和肝素治疗后，出血时间均显著延长，但仍在临床可接受范围内。在接受HBW 023和肝素治疗后，动脉和静脉部分的通畅率均显著提高。在接受HBW 023和肝素治疗后，动脉和静脉部分的血栓物质同时相应减少。在静脉研究中，与肝素组相比，水蛭素（HBW 023）显著提高了血栓物质的减少量。肝素治疗导致预期的高抗Fxa水平和APTT延长，但水蛭素在抗血栓效力方面至少同样有效，仅使治疗前水平略有变化。肝素和水蛭素均使抗Flla水平立即升高（达到最高水平），但在单次剂量水蛭素治疗2小时后降至低水平，尽管同时具有出色的抗血栓作用。我们得出结论，新型重组水蛭素HBW 023与标准肝素一样，在严重血管壁创伤后的小动脉和静脉中都是高效的抗血栓药物。在动脉部分，肝素和HBW 023治疗后出血时间均同时显著延长（仍在可接受范围内），但在静脉部分仅肝素治疗后出血时间延长。此外，重组水蛭素HBW 023的优势在于单次给药。
