PULMONARY RESPONSE TO HYPEROXIA - EFFECTS OF MAGNESIUM

Animals and humans rapidly develop respiratory failure and die within a few days when exposed to 100% oxygen. Postmortem examination of the lungs shows histopathologic features characteristic of diffuse alveola r damage, clinically recognized as adult respiratory distress syndrome (ARDS). Ar the present rime, there is no effective therapy available to alter outcomes in ARDS. Importantly, hypomagnesemia also is frequen tly observed in critically ill patients at risk of developing ARDS. in a model oi hyperoxic lung injury, rats were exposed to 100% oxygen fo r 48, 64, and 96 hr and several experiments were performed. First, cha nges in the features of bronchoalveolar lavage and in alveolar macroph age function were compared in rats exposed to room air and those expos ed to hyperoxia. Second, we studied the effect of hypomagnesemia on th e severity of hyperoxic lung injury. Third, we evaluated the pulmonary responses to high-dose and normal-dose Mg therapy in rats exposed to hyperoxia. In ail groups, hyperoxia induced significant changes in the total and differential cell counts with increased lipid peroxidation of lavaged cells, enhanced chemiluminescence from alveolar macrophages , and protein leakage into the alveolar spaces. After 48 hr of hyperox ia, oxygen-free radical formation and hydrogen peroxide production by the alveolar macrophage were diminished compared to baseline, implying a toxic effect of hyperoxia on the alveolar macrophages. Overall, hyp omagnesemia tended to magnify the degree of hyperoxic lung injury, whi le high-dose Mg therapy tended to attenuate the effects of hyperoxia. In conclusion, in this animal model of diffuse alveolar damage, altera tions in host serum magnesium levels may modulate the degree of lung d amage.