Hobbhahn J, Habazettl H, Conzen P, Peter K
Institut für Anaesthesiologie der Ludwig-Maximilians-Universität München, Klinikum Grosshadern.
Anaesthesist. 1991 Jul;40(7):365-74.
Protamine is a strongly alkaline polypeptide with a molecular weight of about 4500. Protamine solutions contain paraben compounds as antimicrobial agents. Rapid neutralization of heparin by protamine may cause an anaphylactoid reaction characterized by a non-immunogenic histamine release and by unknown mediators mechanisms. This response is associated with systemic peripheral vasodilation resulting in slight to moderate hypotension. Weak negative inotropic effects by mechanisms different from the reduction of ionized calcium concentrations may also contribute to systemic hypotension. Apart from these mostly slight reactions, severe reactions may occur with life-threatening systemic hypotension, bronchospasm and, in rare cases, death. They are caused by anaphylactic/anaphylactoid reactions resulting in catastrophic pulmonary vasoconstriction which induces right and eventually global ventricular failure. Sensitization to protamine (anaphylactic) and anaphylactoid reactions are the underlying mechanisms. The majority of anaphylactic/anaphylactoid reactions are associated with complement activation and the release of anaphylatoxins C3a and C5a. These activate the cyclo-oxygenase pathway of the arachidonic acid metabolism in yet unidentified cells, probably within the lung. As a result, thromboxane and prostaglandins are released. Thromboxane is the pivotal mediator responsible for the pulmonary vasoconstriction and, presumably, also for the bronchospasm during protamine reactions. The pronounced activation of polymorphonuclear leukocytes and the decrease in platelet counts may reflect a mere epiphenomenon. The degree of right ventricular afterload increase at which systemic hypotension requiring immediate therapy would occur depends mainly on the contractile state of the heart. Potential risk patients for severe protamine reactions are depot insulin-dependent diabetics and patients with prior exposure to protamine.
鱼精蛋白是一种分子量约为4500的强碱性多肽。鱼精蛋白溶液含有对羟基苯甲酸酯类化合物作为抗菌剂。鱼精蛋白对肝素的快速中和可能会引发类过敏反应，其特征为非免疫原性组胺释放和不明介质机制。这种反应与全身外周血管扩张有关，导致轻度至中度低血压。通过不同于降低离子钙浓度的机制产生的微弱负性肌力作用也可能导致全身低血压。除了这些大多轻微的反应外，还可能发生严重反应，包括危及生命的全身低血压、支气管痉挛，罕见情况下会导致死亡。它们是由过敏/类过敏反应引起的，导致灾难性的肺血管收缩，进而诱发右心室并最终导致全心室衰竭。对鱼精蛋白的致敏（过敏）和类过敏反应是潜在机制。大多数过敏/类过敏反应与补体激活及过敏毒素C3a和C5a的释放有关。这些物质激活了尚未明确的细胞（可能在肺内）中花生四烯酸代谢的环氧化酶途径。结果，血栓素和前列腺素被释放。血栓素是鱼精蛋白反应期间负责肺血管收缩以及可能导致支气管痉挛的关键介质。多形核白细胞的明显激活和血小板计数的减少可能仅仅反映了一种附带现象。发生需要立即治疗的全身低血压时右心室后负荷增加的程度主要取决于心脏的收缩状态。严重鱼精蛋白反应的潜在风险患者是长效胰岛素依赖型糖尿病患者和既往接触过鱼精蛋白的患者。
