Thromboxane Mediation of Pulmonary Hemodynamic Responses after Neutralization of Heparin by Protamine in Pigs
Thromboxane Mediation of Pulmonary Hemodynamic Responses after Neutralization of Heparin by Protamine in Pigs
复制标题
鱼精蛋白中和肝素后血栓素介导猪的肺血流动力学反应
作者：
P. Conzen;H. Habazettl;Ralph Gutmann;J. Hobbhahn;A. Goetz;K. Peter;W. Brendel
鱼精蛋白中和肝素通常与严重的血液动力学副作用相关，包括肺动脉高压和全身性低血压。由于前列腺素可能参与其中，作者研究了花生四烯酸代谢产物，特别是血栓素A2在这一过程中的作用。在用安氟醚和芬太尼麻醉期间，研究了四组猪：第1组（n = 10）接受肝素（250 IU/kg），15分钟后接受鱼精蛋白（100 mg）中和肝素。第2组（n = 11）采用相同的方案，不同之处在于在鱼精蛋白前5分钟输注血栓烷A2受体拮抗剂BM 13.177（10 mg/kg）。组1的方案也用于组3（n = 7），除了这些动物用吲哚美辛（10 mg/kg）预处理。第4组动物（n = 10）仅给予鱼精蛋白（100 mg）。鱼精蛋白中和肝素后，第1组肺动脉压和肺血管阻力显著增加。这伴随着环氧合酶产物血栓烷B2、6-酮-前列腺素F1α和前列腺素F2α的血浆浓度显著增加。第2组中环氧合酶产物增加至相当程度，但无血流动力学影响。两组的白细胞计数均下降。第3组和第4组中不存在血液动力学反应以及血浆前列腺素水平变化，但仅接受鱼精蛋白的动物中白细胞计数受影响较小。结果表明，鱼精蛋白的血流动力学副作用是由前列腺素介导的，血栓素A2的释放是关键步骤，因为血栓素受体拮抗剂预处理可有效地防止副作用。白细胞或血小板计数与血流动力学改变的严重程度无直接关系。
Protamine neutralization of heparin is often associated with severe hemodynamic side-effects, including pulmonary hypertension and systemic hypotension. Because prostanoids may be involved, the authors studied the role of arachidonic acid metabolites, especially thromboxane A2, in this process. During anesthesia with enflurane and fentanyl, four groups of pigs were studied: Group 1 (n = 10) received heparin (250 IU/kg), followed by protamine (100 mg) after 15 minutes to neutralize the heparin. The same protocol was used in group 2 (n = 11), except that the thromboxane A2 receptor antagonist BM 13.177 (10 mg/kg) was infused 5 minutes before the protamine. The protocol for group 1 was also used for group 3 (n = 7) except that these animals were pretreated with indomethacin (10 mg/kg). Animals in group 4 (n = 10) were given protamine only (100 mg). Pulmonary artery pressure and pulmonary vascular resistance increased significantly in group 1 after protamine neutralization of heparin. This was accompanied by significant increases in plasma concentrations of the cyclooxygen-ase products thromboxane B2, 6-keto-prostaglandin F1α, and prostaglandin F2α. Cyclooxygenase products increased to comparable degrees in group 2, but without hemodynamic effects. Leukocyte counts decreased comparably in both groups. Hemodynamic reactions, as well as changes in plasma prostanoid levels were absent in group 3, and group 4, but leukocyte counts were less affected in animals that received protamine alone. The results indicate that the hemodynamic side-effects of protamine are mediated by prostanoids and that thromboxane A2 release is the pivotal step, because side effects were effectively prevented by pretreatment with a thromboxane receptor antagonist. Leukocyte or platelet counts were not directly related to the severity of hemodynamic alterations.