Free radicals mediate amphetamine-induced acute pulmonary edema in isolated rat lung

Intravenous amphetamine abuse may cause serious cardiopulmonary complications via unknown mechanisms. We investigated the role of free radicals in the amphetamine-induced lung injury using isolated rat lungs. Adding amphetamine into the perfusate caused dose-dependent increases in perfusion pressure and lung weight. Amphetamine increased the filtration coefficient (K(f)) by 90 +/- 20% and 210 +/- 10% at doses of 10 microM and 50 microM, respectively, as compared to the baseline level. Pretreatment with dimethylthiourea (DMTU), an oxygen radical scavenger, abolished the pulmonary hypertension, lung weight gain, and permeability changes. We also examined the effect of amphetamine on free radical generation in polymorphonuclear leukocytes (PMN). Adding phorbol myristate acetate (PMA, 1 nM) enhanced the chemiluminescence indicating the functional viability of the isolated PMN. Amphetamine (50 microM) significantly enhanced the chemiluminescence generation of PMN by 152 +/- 26% as compared with the baseline value. Combination of amphetamine and PMA increased free radical formation by 360 +/- 85%. In summary, our results showed that amphetamine may cause acute lung injury by overproduction of free radicals. Although amphetamine can activate PMN, the source of free radicals remains to be determined.