Differing effects of nitrogen mustard and hydroxyurea on lung O2 toxicity in adult sheep.

We measured the effects of leukocyte depletion on the pulmonary response to breathing 100% O2 in adult sheep, using two dissimilar agents. A group of eight sheep received 4.0 g/day of hydroxyurea for 4 to 6 days, and six sheep received two to four doses of 0.4 mg/kg of nitrogen mustard before exposure to 100% O2. A group of seven sheep breathed 100% O2 with no drug treatment. A group of five control sheep breathed compressed air for 96 h. Hydroxyurea selectively reduced circulating neutrophils (602 ± 245 neutrophils, 2,537 ± 394 lymphocytes per mm3), and nitrogen mustard decreased both circulating neutrophils (633 ± 326) and lymphocytes (521 ± 129). In untreated sheep breathing 100% O2, survival time was 92.6 ± 3.4 h and postmortem blood-free lung water to dry lung ratio was 4.4 ± 0.2. Hydroxyurea significantly delayed the onset of oxygen toxicity as measured by changes in lung lymph flow, PaO2, PaCO2, and time to respiratory failure (111.8 ± 7.7 h), although the degree of final lung injury was unchanged ...