EFFECTS OF N-ACETYLCYSTEINE ON DIAPHRAGMATIC FUNCTION AND MALONDIALDEHYDE CONTENT IN ESCHERICHIA-COLI ENDOTOXEMIC RATS

We evaluated the effects of sublethal Escherchia coli endotoxemia with or without concomitant administration of N-acetylcysteine, an antioxidant agent, on a diaphragmatic strength, endurance, and malondialdehyde (MDA) content in rats. One hundred ninety rats were inoculated subcutaneously on 2 successive days with 0.6 and 1.2 mg/100 g body weight of E. coli lipopolysaccharide respectively (E animals, n = 100) or saline (C group, n = 90). E and C animals were divided into two groups based on administration of endotoxin or saline alone (E group, n = 55; C group, n = 47, respectively) or endotoxin or saline plus N-acetylcysteine (1 g/kg body weight/day intraperitoneally) (E-NAC group, n = 45; C-NAC group, n = 43, respectively). Diaphragmatic strength was assessed in vivo 48 h after the first endotoxin or saline administration by measuring the transdiaphragmatic pressure (Pdi) generated during electrical stimulation of the phrenic nerves at 0.5, 10, 20, 30, 50, and 100 Hz. Endurance index was calculated as the percent ratio of Pdi generated after 30 s of phrenic stimulation at 10 Hz divided by the initial force. Diaphragmatic MDA (fluorometric technique) was measured 0, 6, 18, 30, 42, and 48 h after the first dose of endotoxin or saline. Pdi for 50 and 100 Hz was significantly reduced in Group E as compared with group C. This phenomenon was associated with a reduced endurance performance as assessed by a lower diaphragmatic endurance index In E as compared with C animals (90.9 +/- 4.2 versus 114.3 +/- 4.1 respectively; p < 0.01). Diaphragmatic MDA content (nM/mg prot) was significantly higher in E as compared with C animals 18 h (0.99 +/- 0.17 versus 0.53 +/- 0.05; p < 0.05) and 42 h (+/- 0.12 versus 0.46 +/- 0.03; p < 0.05) after the first endotoxin or saline inoculation. N-acetylcysteine administration prevented both the reduction in diaphragmatic strength and endurance and the increase in muscle MDA content observed during E. coli endotoxemia. These results suggest that diaphragmatic dysfunction during sublethal endotoxemia could be related to reactive oxygen metabolites.