Effects of controlled mechanical ventilation on sepsis-induced diaphragm dysfunction in rats.

OBJECTIVES: Diaphragm dysfunction develops during severe sepsis as a consequence of hemodynamic, metabolic, and intrinsic abnormalities. Similarly, 12 hours of controlled mechanical ventilation also promotes diaphragm dysfunction. Importantly, patients with sepsis are often treated with mechanical ventilation for several days. It is unknown if controlled mechanical ventilation exacerbates sepsis-induced diaphragm dysfunction, and this forms the basis for these experiments. We investigate the effects of 12-hour controlled mechanical ventilation on contractile function, fiber dimension, cytokine production, proteolysis, autophagy, and oxidative stress in the diaphragm of septic rats. DESIGN: Randomized controlled experiment. SETTING: Animal research laboratory. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: Treatment with a single intraperitoneal injection of either saline or Escherichia coli lipopolysaccharide (5 mg/kg). After 12 hours, the saline-treated animals (controlled mechanical ventilation) and half of the septic animals (lipopolysaccharide + controlled mechanical ventilation) were submitted to 12 hours of controlled mechanical ventilation while the remaining septic animals (lipopolysaccharide) were breathing spontaneously for 12 hours. They were compared to a control group. All animals were studied 24 hours after saline or lipopolysaccharide administration. MEASUREMENTS AND MAIN RESULTS: Twenty-four hours after saline or lipopolysaccharide administration, diaphragm contractility was measured in vitro. We also measured diaphragm muscle fiber dimensions from stained cross sections, and inflammatory cytokines were determined by proteome array. Activities of calpain, caspase-3, and proteasome, expression of 20S-proteasome α subunits, E2 conjugases, E3 ligases, and autophagy were measured with immunoblotting and quantitative polymerase chain reaction. Lipopolysaccharide and/or controlled mechanical ventilation independently decreased diaphragm contractility and fiber dimensions and increased diaphragm interleukin-6 production, protein ubiquitination, expression of Atrogin-1 and Murf-1, calpain and caspase-3 activities, autophagy, and protein oxidation. Compared with lipopolysaccharide alone, lipopolysaccharide + controlled mechanical ventilation worsened diaphragm contractile dysfunction, augmented diaphragm interleukin-6 levels, autophagy, and protein oxidation, but exerted no exacerbating effects on diaphragm fiber dimensions, calpain, caspase-3, or proteasome activation. CONCLUSIONS: Twelve hours of controlled mechanical ventilation potentiates sepsis-induced diaphragm dysfunction, possibly due to increased proinflammatory cytokine production and autophagy and worsening of oxidative stress.

Body-related envy: a social comparison perspective in sport and exercise.

These three studies sought to better understand experiences of body-related envy and to examine the association with motivation and exercise behavior in young adult males and females. In an interview study, participants (N = 11) discussed body-related envy within a framework of social comparison. In Study 2, a thematic content analysis was conducted on self-reported narratives of body-related envy experiences reported by 288 participants. Themes of body-related envy triggers, cognitions, and cognitive and behavioral outcomes were identified. Findings from Studies 1 and 2 highlighted the possible link between body-related envy and exercise motivation and behavior. Study 3 tested these associations with males and females (N = 595) who completed a self-report questionnaire. In the structural equation model, body-related envy was positively associated with external, introjected, and identified regulations, and identified regulation was positively associated with exercise behavior. Taken together, the importance of body-related envy in the experience of cognitive, affective, and behavioral outcomes related to sport and exercise contexts is highlighted.