Diaphragmatic fatigue during sepsis-Mechanisms and therapy

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We investigated the alteration and mechanisms in diaphragmatic contractility in intra-abdominal sepsis in vitro. Intra-abdominal sepsis was produced using the cecal ligation and perforation technique (CLP). We assessed the diaphragmatic contractility by twitch characteristics and force-frequency curves in vitro. In the first study, we investigated the time course changes in diaphragmatic contractility after CLP. Diaphragmatic contractile dysfunction was began to develop 10hr after CLP and further reduction was observed 16hr after CLP. In the second study, we investigated the effects of PEG-SOD, PEG-CAT and DMSO on diaphragmatic contractility and MDA levels in septic peritonitis and the activities of two main antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx) in vitro. PEG-SOD, PEG-CAT and DMSO were administered intraperitoneally 30 min before and 12h after CLP. Diaphragmatic MDA levels were significantly elevated after CLP. PEG=SOD, PEG-CAT and DMSO significantly improved diaphragmatic contractility and prevented the elevation in diaphragmatic MDA levels after CLP. Diaphragmatic SOD activities were significantly increased after CLP. These results suggest that several types of oxygen-derived free radicals play a role in the reduction in diaphragmatic contractility after CLP.