Alteration in diaphragmatic contractility during septic peritonitis in rats: effect of polyethylene glycol-absorbed superoxide dismutase

OBJECTIVES: To assess the alterations in diaphragmatic contractility measured in vitro during experimental septic peritonitis and to evaluate the effect of polyethylene glycol-absorbed superoxide dismutase (PEG-SOD) on the alterations in contractility. DESIGN: Prospective, randomized, controlled animal trial. SETTING: Research laboratory. SUBJECTS: A total of 321 male Wistar rats, weighing 250-300 g. INTERVENTIONS: Rats were treated with cecal ligation and puncture (CLP). In the first experiment, diaphragmatic contractility was measured at 4, 10, 12, and 16 hrs after CLP. In the second experiment, PEG-SOD (4,000 units/kg) was administered intraperitoneally, and then diaphragmatic contractility was measured at 10 and 16 hrs after CLP. Levels of lipid peroxides and antioxidant enzymes in the diaphragm tissue were measured at 10 and 16 hrs after CLP. MEASUREMENTS AND MAIN RESULTS: In experiment 1, diaphragmatic twitch characteristics and force-frequency relationships were determined at 4, 10, 12, and 16 hrs after CLP. In experiment 2, the effects of administration of PEG-SOD on twitch characteristics and force-frequency relationships were determined at 10 and 16 hrs after CLP. The levels of diaphragmatic thiobarbituric acid reactive substances and superoxide dismutase (SOD) and glutathione peroxidase activities were measured at 10 and 16 hrs after CLP. Twitch tension and force-frequency curves were significantly lower in the CLP groups than in the sham-operated group. Administration of PEG-SOD attenuated the reduction in twitch tension and the downward shift of force-frequency curves after CLP. Diaphragmatic levels of thiobarbituric acid reactive substances increased after CLP. However, the administration of PEG-SOD prevented increases in levels of diaphragmatic thiobarbituric acid reactive substances after CLP. Diaphragmatic SOD activity, but not glutathione peroxidase activity, was increased after CLP. CONCLUSIONS: Intra-abdominal sepsis (CLP) induced a marked reduction in diaphragmatic contractility, but PEG-SOD attenuated this reduction. Therefore, we conclude that oxygen-derived free radicals play an important role in the alterations in diaphragmatic contractility during intra-abdominal sepsis.