O'Flaherty J T, Cousart S, Lineberger A S, Bond E, Bass D A, DeChatelet L R, Leake E S, McCall C E
Am J Pathol. 1980 Oct;101(1):79-92.
Phorbol myristate acetate is a potent aggregator of platelets. It was found that it was similarly potent in aggregating neutrophils and in producing striking thrombocytopenia and neutropenia when infused intravenously into rabbits. Aggregation and cytopenia were further correlated in that both types of responses developed abruptly and persisted for more than 90 minutes. Animals infused with 40 microgram/kg of the phorbol ester exhibited moderately severe respiratory distress. Their respiratory rate doubled shortly after the infusion, and this tachypnea persisted for more than 2 hours. At necroscopic examination, the lungs of these rabbits contained two outstanding abnormalities: numerous foci of alveolar hemorrhage and extensive intravascular accumulations of platelets and neutrophils. Thus, these animals had evidence of increased permeability and potential occlusion of the pulmonary microvasculature. Increased permeability, occlusion of lung blood vessels, or the occurrence of both processes was further indicated in studies on animals pre-infused with the plasma protein marker 125I-albumin: animals infused with the phorbol ester had a significantly increased amount of this label in their lungs in spite of thorough postmortem perfusion of their pulmonary vasculature with saline and fixative. We conclude that phorbol myristate acetate has actions in vivo that resemble those of a variety of other platelet (eg, arachidonic acid) and neutrophil (eg, chemotactic factors) aggregating agents that cause cytopenia and lung dysfunction. However, compared with these other agents, the phorbol ester produces respiratory distress of intermediate severity and greater duration. The drug, therefore, induces a syndrome that more closely resembles that seen in a variety of clinical and experimental conditions that associate shocklike states with cytopenia and lung dysfunction. It may serve as a useful tool in the study of the pathophysiology of these states as well as in those produced by other aggregating agents.
佛波醇肉豆蔻酸酯乙酸盐是一种强效的血小板聚集剂。研究发现，它在使嗜中性粒细胞聚集以及静脉注射到兔子体内时产生显著的血小板减少和嗜中性粒细胞减少方面同样具有强效。聚集和血细胞减少进一步相关，因为这两种类型的反应都突然出现并持续超过90分钟。注入40微克/千克佛波醇酯的动物表现出中度严重的呼吸窘迫。注入后不久，它们的呼吸频率加倍，这种呼吸急促持续超过2小时。尸检时，这些兔子的肺部有两个明显异常：大量肺泡出血灶以及血小板和嗜中性粒细胞在血管内广泛积聚。因此，这些动物有肺微血管通透性增加和潜在阻塞的证据。在对预先注入血浆蛋白标记物125I-白蛋白的动物进行的研究中，进一步表明了通透性增加、肺血管阻塞或这两个过程的发生：尽管在死后用盐水和固定剂对其肺血管进行了充分灌注，但注入佛波醇酯的动物肺部这种标记物的含量仍显著增加。我们得出结论，佛波醇肉豆蔻酸酯乙酸盐在体内的作用类似于多种其他导致血细胞减少和肺功能障碍的血小板（如花生四烯酸）和嗜中性粒细胞（如趋化因子）聚集剂的作用。然而，与这些其他药物相比，佛波醇酯产生的呼吸窘迫程度中等且持续时间更长。因此，该药物诱发的综合征更类似于在多种临床和实验条件下所见到的、将休克样状态与血细胞减少和肺功能障碍相关联的综合征。它可能是研究这些状态以及其他聚集剂所产生状态的病理生理学的有用工具。
