Evaluation of a leukotriene receptor antagonist in prevention of hyperoxic lung injury in newborn rabbits.
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.
Kertesz
N J
NJ
Department of Pediatrics, Evanston Hospital, Northwestern University Medical School, Illinois 60201.
Holtzman
R B
RB
Adler
L
L
Hageman
J R
JR
D000818:Animals; D005609:Free Radicals; D007191:Indazoles / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D055370:Lung Injury; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010100:Oxygen; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D011817:Rabbits; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D018077:Receptors, Leukotriene
D005609:Free Radicals; D007191:Indazoles; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; C054217:ICI 198615; D010100:Oxygen