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PubMed1993

Effect of free radical scavengers on endotoxin-induced respiratory muscle dysfunction.

Recent studies have suggested that free radicals contribute to the diaphragmatic dysfunction observed in sepsis. However, previous work has not determined which species of free radicals are responsible for producing these effects or whether the intercostal muscles are affected similarly during sepsis. The purpose of this study was to examine these issues using a hamster model of endotoxin-mediated sepsis in which diaphragm and intercostal muscle function was assessed on muscle strips excised from these animals after killing. Several groups of animals were studied, including animals injected with (1) saline, (2) endotoxin, (3) endotoxin plus active PEG-SOD, a superoxide scavenger, (4) endotoxin plus active PEG-catalase, a hydrogen peroxide scavenger, (5) endotoxin plus DMSO, a hydroxyl scavenger, and (6) endotoxin plus denatured PEG-SOD. We found that endotoxin administration elicited significant reductions in diaphragm and intercostal muscle contractility. In each of the three groups of animals to which active free radical scavengers were administered, the effects of endotoxin were attenuated. Denatured PEG-SOD did not protect the respiratory muscles from endotoxin-mediated dysfunction, however. These data indicate that both the diaphragm and intercostal muscles are affected similarly by sepsis; moreover, several free radical species (superoxide ions, hydrogen peroxide, and hydroxyl ions) play a role in mediating this type of injury.

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PubMed1992

Effect of PEG-superoxide dismutase on the diaphragmatic response to endotoxin.

Although it is known that endotoxin can induce diaphragmatic dysfunction, the mechanism of this effect is not fully understood. However, because the effects of endotoxin on other tissues appear to be mediated in part by free radicals, the present study sought to determine if free radicals may also contribute to the diaphragmatic dysfunction induced by endotoxin administration. Studies were performed on four groups of hamsters. One group of animals received intraperitoneal injections of endotoxin on the first and second days of study (i.e., 10 and 20 mg/kg, respectively). The second group received saline rather than endotoxin, the third group received both endotoxin and a free radical scavenger, PEG-SOD (2,000 U/kg given intraperitoneally every 12 h on Days 1 and 2), and the fourth group received PEG-SOD alone. All groups were killed on the third study day (i.e., 48 h after the initial injections). Diaphragmatic contractile function was assessed in vitro using muscle strips excised from the costal diaphragms of freshly killed animals; diaphragm samples were also assayed for malondialdehyde (MDA), a commonly used index of free-radical-mediated lipid peroxidation. MDA levels were higher in diaphragms from endotoxin-treated animals than from saline-treated control animals, and the contractility of diaphragm strips from endotoxin-treated animals was reduced when compared with strips from saline-treated control animals. Administration of PEG-SOD prevented MDA formation and contractile dysfunction in endotoxin-treated animals. Diaphragm contractility and MDA levels for animals given PEG-SOD alone were similar to those for saline-treated control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗