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 A(2) (TXA(2)) participated in the
lung injury and have evaluated the efficacy of
ozagrel, a TXA(2) synthase inhibitor, on the
lung injury in guinea-pigs.
Oleic acid injection increased the plasma level of TXB(2), a stable metabolite of TXA(2), and the time-course of plasma TXB(2) was similar to that of the decreased partial
oxygen pressure of arterial blood (Pao(2)) induced with
oleic acid.
Ozagrel administered intravenously 30 min before
oleic acid injection prevented the decrease in Pao(2) and pulmonary vascular hyper-permeability. It also prevented increases in
lactate dehydrogenase activity, a measure of lung cell injury, TXB(2 )and its weight ratio to 6-keto
prostaglandin F(1alpha) in bronchoalveolar lavage fluid. Although
ozagrel administered simultaneously with
oleic acid ameliorated the decrease in Pao(2), post treatment showed little effect. We suggest that TXA(2) participated in the
oleic acid lung injury, as an "early phase" mediator, and rapidly-acting TXA(2) synthase inhibitors were effective in the prevention of
acute lung injury.