Involvement of thromboxane A2 (TXA2) in the early stages of oleic acid-induced lung injury and the preventive effect of ozagrel, a TXA2 synthase inhibitor, in guinea-pigs

Abstract

An intravenous injection of oleic acid into animals can produce a lung injury with hypoxaemia and pulmonary vascular hyper-permeability. Although oleic acid lung injury is used as a model of acute respiratory distress syndrome (ARDS), the precise mechanisms of the lung injury are still unclear. We have investigated whether thromboxane A2 (TXA2) participated in the lung injury and have evaluated the efficacy of ozagrel, a TXA2 synthase inhibitor, on the lung injury in guinea-pigs. Oleic acid injection increased the plasma level of TXB2, a stable metabolite of TXA2, and the time-course of plasma TXB2 was similar to that of the decreased partial oxygen pressure of arterial blood (Pao2) induced with oleic acid. Ozagrel administered intravenously 30 min before oleic acid injection prevented the decrease in Pao2 and pulmonary vascular hyper-permeability. It also prevented increases in lactate dehydrogenase activity, a measure of lung cell injury, TXB2 and its weight ratio to 6-keto prostaglandin F1 α in bronchoalveolar lavage fluid. Although ozagrel administered simultaneously with oleic acid ameliorated the decrease in Pao2, post treatment showed little effect. We suggest that TXA2 participated in the oleic acid lung injury, as an “early phase” mediator, and rapidly-acting TXA2 synthase inhibitors were effective in the prevention of acute lung injury.