Habazettl H, Martinek V, Vollmar B, Conzen P
Institute for Surgical Research, Klinikum Grosshadern, University of Munich, Germany.
J Thorac Cardiovasc Surg. 1997 Apr;113(4):784-91. doi: 10.1016/S0022-5223(97)70238-1.
A transient but severe systemic leukopenia regularly occurs after the antagonization of heparin by protamine in patients and in animals. The aim of the present study was to investigate the site and mechanisms of white blood cell retention during this transient leukopenia by studying the leukocyte-endothelial cell interaction in skeletal muscle venules.
Syrian golden hamsters were equipped with a dorsal skinfold chamber for intravital fluorescence microscopy and arterial and venous catheters for drug infusion, blood pressure measurement, and blood sampling. Microhemodynamic parameters and leukocyte-endothelial cell interactions were observed in one single collecting venule per animal after intravenous infusion of saline solution (control, n = 10), of protamine (n = 9), and after infusion of heparin followed by either intravenous protamine (n = 9) or intraarterial protamine (n = 9).
All parameters remained unchanged in the control group. Whereas venular diameters remained unchanged, protamine transiently increased arterial blood pressure and venular erythrocyte velocity in all groups. Systemic leukocyte counts and the venular leukocyte discharge concentration decreased concurrently after protamine administration by about 60% to 70% at 2 minutes while the fraction of rolling leukocytes and the number of adherent leukocytes remained unchanged. Two and one-half minutes later, systemic leukocyte counts and venular discharge concentrations normalized while the fraction of leukocytes rolling slowly along or adhering firmly to the venular endothelial wall increased considerably and similarly in all groups receiving protamine. Myeloperoxidase (an indicator of polymorphonuclear leukocytes) determination in 20 separate hamsters 2 minutes after protamine infusion revealed increased myeloperoxidase activity exclusively in the lungs.
The response of leukocytes to protamine infusion with or without prior heparinization is biphasic: initial retention of leukocytes in the lungs is followed by enhanced leukocyte-endothelial cell interaction in the systemic circulation.
在患者和动物中，用鱼精蛋白中和肝素后会定期出现短暂但严重的全身性白细胞减少。本研究的目的是通过研究骨骼肌微静脉中的白细胞 - 内皮细胞相互作用，来探究这种短暂性白细胞减少期间白细胞滞留的部位和机制。
给叙利亚金黄地鼠配备用于活体荧光显微镜检查的背部皮褶小室以及用于药物输注、血压测量和血液采样的动静脉导管。在每只动物静脉输注生理盐水（对照组，n = 10）、鱼精蛋白（n = 9）以及输注肝素后再静脉输注鱼精蛋白（n = 9）或动脉输注鱼精蛋白（n = 9）后，观察单个收集微静脉中的微观血流动力学参数和白细胞 - 内皮细胞相互作用。
对照组所有参数均保持不变。虽然微静脉直径不变，但鱼精蛋白使所有组的动脉血压和微静脉红细胞速度短暂升高。给药后2分钟，鱼精蛋白使全身白细胞计数和微静脉白细胞排出浓度同时下降约60%至70%，而滚动白细胞比例和黏附白细胞数量保持不变。2分半钟后，全身白细胞计数和微静脉排出浓度恢复正常，而在所有接受鱼精蛋白的组中，沿微静脉内皮壁缓慢滚动或牢固黏附的白细胞比例均显著增加且相似。鱼精蛋白输注2分钟后，对20只单独的地鼠进行髓过氧化物酶（多形核白细胞的指标）测定，结果显示仅肺中的髓过氧化物酶活性增加。
无论是否预先肝素化，白细胞对鱼精蛋白输注的反应都是双相的：最初白细胞滞留在肺中，随后全身循环中的白细胞 - 内皮细胞相互作用增强。
