OXIDANT-ANTIOXIDANT BALANCE IN GRANULOCYTES DURING ARDS - EFFECT OF N-ACETYLCYSTEINE

The production of cytotoxic oxygen radicals by activated granulocytes is a proposed mechanism of lung injury in ARDS. Protective effects of N-acetylcysteine (NAG) have been described in experimental and clinica l ARDS, NAC could act in part by replenishing the intracellular stores of glutathione (GSH) in activated granulocytes, leading to detoxifica tion of oxygen radicals produced by these cells, To test this hypothes is, 16 patients in the early phase of ARDS were randomized to receive either NAC (n=8) or placebo (n=8); granulocyte GSH, granulocyte oxygen radical production, and plasma levels of granulocyte elastase were me asured in blood samples drawn sequentially within 8 h after the onset of ARDS (day 0), and then 24 (day 1), 72 (day 3), and 120 h (day 5) af ter the first sample; treatment with NAC or placebo was started immedi ately after day 0 and stopped just after day 3. Granulocyte GSH was si gnificantly higher on days 1 and 3 when NAC was received by the patien t. Unstimulated oxygen radical production, as measured ex vivo by lumi nol- and lucigenin-amplified chemiluminescence (CL), was higher in gra nulocytes from ARDS patients than from healthy control subjects, but w as not influenced by NAG. The plasma levels of granulocyte elastase we re five to eight times above the upper normal limit on day 0, decrease d steadily until day 5, and were uninfluenced by NAC. In summary, pare nteral NAC treatment started within 8 h of diagnosis increases the int racellular GSH in the granulocytes of ARDS patients without decreasing spontaneous oxidant production by these cells, The mechanisms of the protective effects of this drug previously reported in experimental an d clinical ARDS remain to be extablished.