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

Objectives: To assess the alterations in diaphragmatic contractility measur ed in vitro during experimental septic peritonitis and to evaluate the effe ct of polyethylene glycol-absorbed superoxide dismutase (PEG-SOD) on the al terations 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, 1 2, and 16 hrs after CLP. In the second experiment, PEG-SOD (4000 units/kg) was administered intraperitoneally, and then diaphragmatic contractility wa s measured at 10 and 16 hrs after CLP, Levels of lipid peroxides and antiox idant enzymes in the diaphragm tissue were measured at 10 and 16 hrs after CLP, Measurements and Main Results: In experiment 1, diaphragmatic twitch charac teristics and force-frequency relationships were determined at 4, 10, 12, a nd 16 hrs after CLP, In experiment 2, the effects of administration of PEG- SOD on twitch characteristics and force-frequency relationships were determ ined at 10 and 16 hrs after CLP. The levels of diaphragmatic thiobarbituric acid reactive substances and superoxide dismutase (SOD) and glutathione pe roxidase activities were measured at 10 and 16 hrs after CLP, Twitch tensio n and force-frequency curves were significantly lower in the CLP groups tha n in the sham-operated group. Administration of PEG-SOD attenuated the redu ction in twitch tension and the downward shift of force-frequency curves af ter CLP, Diaphragmatic levels of thiobarbituric acid reactive substances in creased after CLP, However, the administration of PEG-SOD prevented increas es in levels of diaphragmatic thiobarbituric acid reactive substances after CLP, Diaphragmatic SOD activity, hut not glutathione peroxidase activity, was increased after CLP, Conclusions: Intra-abdominal sepsis (CLP) induced a marked reduction in dia phragmatic contractility, hut PEG-SOD attenuated this reduction. Therefore, we conclude that oxygen-derived free radicals play an important role in th e alterations in diaphragmatic contractility during intra-abdominal sepsis.