Habazettl H, Conzen P F, Vollmar B, Yekebas E, Peter K
Department of Surgery Innenstadt, Klinikum Grosshadern, University of Munich, Federal Republic of Germany.
J Appl Physiol (1985). 1992 Jul;73(1):44-9. doi: 10.1152/jappl.1992.73.1.44.
Heparin neutralization by protamine after cardiac surgery and cardiopulmonary bypass may be associated with complement activation, transient leukopenia, thromboxane A2 release, and severe pulmonary hypertension. The role of leukocytes in the heparin-protamine reaction was studied in leukopenic pigs (n = 9) and a control group (n = 8). Leukopenia was induced by pretreatment with cyclophosphamide (30 mg.kg-1.day-1) for 6-7 days. During general anesthesia and after catheterization, baseline recordings of hemodynamics were performed and blood samples were withdrawn. Heparin (250 IU/kg) was injected and measurements were repeated after 10 min. Protamine sulfate (100 mg) was then infused over 2 min and measurements were performed after 2, 5, and 15 min. Prostanoid concentrations were measured by radioimmunoassays. In additional in vitro experiments, the release of thromboxane B2 from washed platelets and leukocytes after heparin-protamine stimulation was measured. Pretreatment with cyclophosphamide reduced leukocyte counts by 95.5% and the number of neutrophils by greater than 99.9%. Protamine infusion increased mean pulmonary arterial pressure by 74 and 46% and pulmonary vascular resistance by 185 and 384% in control and leukopenic animals, respectively. Thromboxane B2 concentrations increased in both groups. Stimulation by heparin, protamine, or heparin and protamine in sequence did not induce any thromboxane A2 release from washed blood cells. It is concluded that leukocytes do not contribute to pulmonary hypertension after heparin-protamine.
心脏手术和体外循环后鱼精蛋白对肝素的中和作用可能与补体激活、短暂性白细胞减少、血栓素A2释放及严重肺动脉高压有关。在白细胞减少的猪（n = 9）和对照组（n = 8）中研究了白细胞在肝素-鱼精蛋白反应中的作用。通过环磷酰胺预处理（30mg·kg-1·天-1）6 - 7天诱导白细胞减少。在全身麻醉期间及插管后，进行血流动力学的基线记录并采集血样。注射肝素（250IU/kg），10分钟后重复测量。然后在2分钟内输注硫酸鱼精蛋白（100mg），并在2、5和15分钟后进行测量。通过放射免疫测定法测量前列腺素浓度。在另外的体外实验中，测量肝素-鱼精蛋白刺激后洗涤血小板和白细胞中血栓素B2的释放。环磷酰胺预处理使白细胞计数减少95.5%，中性粒细胞数量减少超过99.9%。在对照组和白细胞减少的动物中，输注鱼精蛋白分别使平均肺动脉压升高74%和46%，肺血管阻力升高185%和384%。两组中血栓素B2浓度均升高。肝素、鱼精蛋白或肝素与鱼精蛋白依次刺激均未诱导洗涤血细胞释放任何血栓素A2。结论是白细胞在肝素-鱼精蛋白后所致的肺动脉高压中不起作用。
