Laurindo F R, Goldstein R E, Davenport N J, Ezra D, Feuerstein G Z
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
J Appl Physiol (1985). 1989 Jun;66(6):2681-90. doi: 10.1152/jappl.1989.66.6.2681.
Platelet-activating factor (PAF) is a phospholipid mediator that induces cardiovascular collapse and release of the secondary mediator thromboxane A2 (TxA2). To clarify mechanisms involved in this collapse and, specifically, the relative contribution of left ventricular and right ventricular dysfunction, we studied 12 open-chest pigs. PAF infusion (0.04-0.28 nmol.kg-1.min-1) induced a 5- to 120-fold increase in pulmonary vascular resistance, a 75-98% fall in cardiac output, and systemic arterial hypotension. Right ventricular failure was indicated by chamber enlargement, decreased shortening, and increased right atrial pressures. In contrast, left ventricular dysfunction was accompanied by decreases in chamber dimensions and filling pressures that were unresponsive to volume expansion. U 46619 (a stable TxA2 analogue) and mechanical pulmonary artery constriction induced changes similar to PAF. In 11 additional closed-chest pigs, TxA2 blockade with indomethacin attenuated the PAF-induced rise in pulmonary vascular resistance, right ventricular dysfunction, and systemic hypotension. A specific TxA2 synthase inhibitor, OKY-046, also diminished hemodynamic effects of PAF in six other pigs. Tachyphylaxis was not observed in five pigs repeatedly given PAF. We conclude that acute right ventricular failure as the result of severe increase in pulmonary vascular resistance is the primary mechanism early in the course of PAF-induced shock in the pig. PAF-induced release of TxA2 may contribute significantly to these events.
血小板活化因子（PAF）是一种磷脂介质，可诱发心血管衰竭并释放次级介质血栓素A2（TxA2）。为了阐明参与这种衰竭的机制，特别是左心室和右心室功能障碍的相对作用，我们研究了12只开胸猪。输注PAF（0.04 - 0.28 nmol·kg⁻¹·min⁻¹）可使肺血管阻力增加5至120倍，心输出量下降75 - 98%，并导致体循环动脉低血压。右心室衰竭表现为心室扩大、缩短率降低和右心房压力升高。相比之下，左心室功能障碍则伴有心室尺寸和充盈压降低，且对容量扩张无反应。U 46619（一种稳定的TxA2类似物）和机械性肺动脉收缩引起的变化与PAF相似。在另外11只闭胸猪中，用吲哚美辛阻断TxA2可减轻PAF诱导的肺血管阻力升高、右心室功能障碍和体循环低血压。一种特异性TxA2合酶抑制剂OKY - 046在另外6只猪中也减弱了PAF的血流动力学效应。在5只反复给予PAF的猪中未观察到快速耐受性。我们得出结论，在猪中，PAF诱导的休克过程早期，肺血管阻力严重增加导致的急性右心室衰竭是主要机制。PAF诱导的TxA2释放可能对这些事件有显著贡献。
