Idell S, Peterson B T, Gonzalez K K, Gray L D, Bach R, McLarty J, Fair D S
Department of Medicine, University of Texas Health Center, Tyler 75710.
Am Rev Respir Dis. 1988 Nov;138(5):1282-94. doi: 10.1164/ajrccm/138.5.1282.
Extravascular, primarily intra-alveolar, fibrin deposition is a histologic hallmark of acute lung injury in humans and experimental animals, but the mechanisms leading to this finding are poorly understood. To determine whether local abnormalities in the fibrinolytic-procoagulant balance contribute to alveolar fibrin deposition in acute lung injury, we studied bronchoalveolar lavage (BAL) fluids of anesthetized sheep that received intravenous oleic acid. Prominent alveolar fibrin deposition was observed within 2 h after oleic acid-induced lung injury. Procoagulant and fibrinolytic activities were determined in BAL samples of anesthetized, mechanically ventilated sheep before and 2 h after intravenous oleic acid or saline. BAL procoagulant activity was found to be due mainly to tissue factor associated with Factor VII. In baseline BAL samples, we found relatively low levels of procoagulant activity and relatively high levels of fibrinolytic activity. After induction of oleic acid-induced lung injury, the procoagulant activity of BAL was markedly increased, whereas fibrinolytic activity was either depressed or undetectable. Antiplasmin activity was detectable in BAL of sheep after oleic acid-induced lung injury, which contributed at least in part to the depressed fibrinolytic activity observed. These perturbations occurred with the appearance of extensive alveolar fibrin deposition. In control sheep, BAL fibrinolytic activity was decreased, and antiplasmin activity increased modestly after 2 h of mechanical ventilation, but procoagulant activity was unchanged and alveolar fibrin was not observed. Procoagulant activity in lung lymph and plasma after lung injury did not differ from baseline values, and fibrinolytic activity was undetectable in lymph or plasma samples. These data indicate that increased procoagulant activity and concurrent disruption of the balance of coagulation and fibrinolysis establish local conditions that promote acute fibrin deposition in the alveoli of mechanically ventilated, oleic acid-injured sheep.
血管外，主要是肺泡内纤维蛋白沉积是人类和实验动物急性肺损伤的组织学标志，但导致这一发现的机制尚不清楚。为了确定纤维蛋白溶解-促凝平衡的局部异常是否导致急性肺损伤中的肺泡纤维蛋白沉积，我们研究了接受静脉注射油酸的麻醉绵羊的支气管肺泡灌洗（BAL）液。油酸诱导肺损伤后2小时内观察到明显的肺泡纤维蛋白沉积。在静脉注射油酸或生理盐水之前和之后2小时，测定麻醉、机械通气绵羊的BAL样本中的促凝和纤维蛋白溶解活性。发现BAL促凝活性主要归因于与因子VII相关的组织因子。在基线BAL样本中，我们发现促凝活性水平相对较低，纤维蛋白溶解活性水平相对较高。油酸诱导肺损伤后，BAL的促凝活性显著增加，而纤维蛋白溶解活性则降低或无法检测到。在油酸诱导肺损伤的绵羊的BAL中可检测到抗纤溶酶活性，这至少部分导致了观察到的纤维蛋白溶解活性降低。这些扰动与广泛的肺泡纤维蛋白沉积的出现同时发生。在对照绵羊中，机械通气2小时后，BAL纤维蛋白溶解活性降低，抗纤溶酶活性适度增加，但促凝活性未改变，未观察到肺泡纤维蛋白。肺损伤后肺淋巴和血浆中的促凝活性与基线值无差异，在淋巴或血浆样本中未检测到纤维蛋白溶解活性。这些数据表明，促凝活性增加以及凝血和纤维蛋白溶解平衡的同时破坏建立了局部条件，促进了机械通气、油酸损伤绵羊肺泡中的急性纤维蛋白沉积。
