Heme Oxygenase in Skeletal Muscle

Abstract

Sepsis is a common cause of morbidity and mortality, particularly in elderly, immunocompromised, and critically ill patients. Indeed, severe sepsis is at present the most common cause of death in intensive care unit in the United States (Bone et al., 1992).Respiratory failure is a major clinical manifestation of sepsis, greatly contributing to the mortality of this pathologic condition (Montgomery et al., 1985). In this context, respiratory failure has been traditionally related to the development of adult respiratory distress syndrome (Montgomery et al., 1985). However, different experimental studies demonstrated that an impaired contractile function of respiratory muscles, including the diaphragm, is another important mechanism of respiratory failure during sepsis (Boczkowski et al., 1990 and Boczkowski et al. 1996; El Dwairi et al., 1998; Shindoh et al., 1992; Hussain et al., 1985; Van Surell et al., 1992). Diaphragmatic dysfunction during sepsis appears to be mediated mainly by oxidative stress (Shindoh et al., 1992; Supinski et al., 1996; Van Surell et al., 1992). In fact, we and others have recently shown an increased production of oxidants, such as superoxide anion and peroxynitrite, in the diaphragm of endotoxemic rats (El Dwairi et al, 1998; Boczkowski et al., 1999). The expression of the inducible isoform of nitric oxide (NO) synthase (NOS2) is partly responsible for this effect (Boczkowski et al., 1999).