The pharmacologic activity of leukotriene B< (LTB<) continues to generate intense research interest. LTB4 is known to stimulate degranulation, aggregation, chemotaxis, and chemokinesis of polymorphonuclear leukocytes, as well as promote superoxide generation.1 The proinflammatory effects of this eicosanoid mediator may play a role in the pathogenesis of several inflammatory diseases such as asthma,2 inflammatory bowel disease,3 psoriasis,4 and gout.1*'5 We recently disclosed the acetophenone/ xanthone LTB4 receptor antagonist LY282210 (compound 4, Chart I),6 which evolved from two separate series of compounds represented by LY255283 (1, acetophenone class)7 and LY223982/LY210073 (2/3, benzophenone/

Lung lavage effectively removed inhaled radioactive particles from the lungs in a variety of animal experiments. Several types of lung lavage procedures were used. The removal of several different radionuclides has been studied, including 9sZr-Y5Nb, '44Ce, 239Pu, 23aPu and 24'Am. A single lung lavage in a beagle dog removed about 12% of the initial lung burden (ILB) of the inhaled material. Multiple lung lavages have removed up to 50% of the ILB. A single lung lavage in beagle dogs performed between 2 and 196 days after a single inhalation exposure removed the same percentage of the existing lung burden of '44Ce particles. It was also found that inhaled material with a short lung retention time is poorly removed from the lung by lavage. The removal of radioactive particles with long lung retention times was similar for beagle dogs, baboons and one human. Lung lavage and chelating agents were found effective when used together. In one experiment, the use of lung lavage removed substantial amounts of 144Ce in fused aluminosilicate particles from beagle dogs and prevented the clinical appearance of radiation pneumonitis to 1' 8 months after exposure, whereas, other dogs exposed to the same amounts of '44Ce, but not given lung lavages, died in less than 9 months.

No abstract

The effectiveness of a single, unilateral bronchopulmonary lavage in removing relatively insoluble radioactive material from the lung was evaluated at various times after inhalation exposure to radioactive aerosol in dogs. Twenty-seven beagle dogs exposed to aerosols of 144Ce fused clay achieved initial lung burdens ranging from 23 to 73 pCi/kg body weight. The dogs were divided into nine groups of three dogs each and each group was given a single bronchopulmonary lavage of the right lung at one of the following times after exposure; 2 hr, 2,4,7, 14,28,56,128 and 196 days. Mean percentages of the right lung burden recovered in the lavage fluid were: 45, 25, 22, 19, 25, 12, 17, 14 and 17%, respectively. After the lung lavage, the dogs were sacrificed, dissected, and the tissues analyzed. At least 93 % ofthesacrifice body burden was found in the lungs out to 56 days after exposure. At 128 and 196 days after exposure, lung burdens were means of 88 and 81 % of the sacrifice body burden, respectively.The results indicate that a sizable percentage of the insoluble particles in the lung remains accessible to removal by bronchopulmonary lavage for periods up to 6 months after exposure; however, translocation from the lungs to other tissues increases with time. Also, depending on the isotope, the total radiation dose delivered to lung before lavage can become so large at longer times after exposure that removal of material from the lung has little effect in reducing total cumulative dose to tissues.

The effect of fluid flow rate during bronchopulmonary lavage to remove radioactive particles from the lungs of beagle dogs was investigated. Six adult beagle dogs were exposed by inhalation to aerosols of lUCe in fused clay particles. Four of the dogs were treated with bronchopulmonary lavage of both right and left lungs on day 2 post-exposure. The remaining two dogs were not lavaged and were used to determine the distribution of the inhaled aerosol between the right and left lung. The lavage fluid was introduced into the lung at two flow rates; 0.67 l/min and 1.7 l/min. Lavage of the right lung at the fast rate in two dogs removed 24 and 27% of the right initial lung burden (ILB); lavages of the right lung at the slow rate in the other two dogs removed 35 and 36% of the right IBL. Bronchopulmonary lavage of the left lung of all four dogs, two at the fast rate and two at the slow rate, removed 26,49,23 and 30% of the left ILB, respectively. Total amount removed from both lungs was 2440% of the ILB of lMCe. The order in which the lungs were lavaged did not influence the amount of radiocerium removed. The bilateral procedure did not alter the distribution of material between right and left lung.