Prolonged exposure to
hyperoxia can result in significant
lung injury and has been associated with the development of
bronchopulmonary dysplasia.
Leukotrienes (LT) recruit polymorphonuclear leukocytes (PMN) to the lung, increase vascular permeability, and have therefore been postulated to play a role in the pathogenesis of hyperoxic
lung injury. This study investigates ICI 198,615 (ICI), an
LTD4 and
LTE4 receptor antagonist in preventing hyperoxic
lung injury in newborn rabbits. Matched littermates of 7-day-old rabbits received ICI (0.1 or 1.0 microM/kg/h) or vehicle alone, were exposed to greater than 95% O2, and sacrificed after 48, 72, 84 and 96 h of exposure. Bronchoalveolar alveolar lavage fluid (BAL) of the left lung was analyzed for white cell count, differential, absolute number of PMNs, total
protein, and
cyclooxygenase products
6-keto-PGF1 alpha, and
thromboxane B2. Lung water was quantified utilizing the right lung. Results demonstrated no significant differences between the ICI groups or between the ICI groups and controls. In conclusion, the administration of the
LTD4 and
LTE4 receptor antagonist ICI 198,615 was insufficient to reduce the formation of
pulmonary edema, reduce mortality or attenuate hyperoxic
lung injury. These experiments suggest that a number of other mediators may be involved in the hyperoxic
lung injury process and that the functional inhibition of a portion of the
arachidonic acid cascade was not sufficient to either prevent or attenuate hyperoxic
lung injury in newborn rabbits.