Monocyte inflammatory mediators impair in vitro hamster diaphragm contractility.
Sepsis has been shown to impair ventilatory muscle function. To determine whether this can be attributed to direct effects of inflammatory mediators on muscle fibers, we carried out in vitro studies on hamster costal diaphragm. Baseline measurements included supramaximal peak twitch (Pt) and tetanic tension (Po), twitch half relaxation time (1/2RT) and time-to-peak tension (TTP), and force frequency response (15 to 80 Hz). Fatigability was evaluated using 60-Hz stimulations at a duty cycle of 0.4 until tension fell to 50% of baseline. Preparations were then incubated in one of the following for 60 min: (1) Krebs solution (n = 5), (2) nonstimulated monocyte supernatant (n = 5), or (3) lipopolysaccharide-stimulated monocyte supernatant (n = 5). Baseline Pt, Po, 1/2RT, TTP, force frequency response, and fatigue profile were similar between groups. After incubation there was a significant fall in Pt (mean +/- SD, 538 +/- 65 to 288 +/- 13 g/cm2, p < 0.05) and Po (1,268 +/- 132 to 921 +/- 64 g/cm2, p < 0.05) in the LPS group, with no change in the other groups. There was no change in TTP; however, 1/2RT was lower in the LPS-stimulated group after incubation (p < 0.05). There was a rightward shift in the force frequency response for the LPS-stimulated group (p < 0.05). When normalizing for initial Po, there was no significant change in the time to fatigue for any of the three groups. This study demonstrated that monocyte secretory products impair diaphragmatic contractility in vitro by a direct effect on muscle fibers.(ABSTRACT TRUNCATED AT 250 WORDS)
Wilcox
P
P
Department of Medicine, University of British Columbia, Vancouver, Canada.
Osborne
S
S
Bressler
B
B
D000818:Animals; D016470:Bacteremia / Q000097:blood / Q000150:complications / Q000276:immunology; D006224:Cricetinae; D003964:Diaphragm / Q000187:drug effects* / Q000502:physiology; D004576:Electromyography; D005069:Evaluation Studies as Topic; D066298:In Vitro Techniques; D007249:Inflammation; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D008647:Mesocricetus; D009000:Monocytes / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects*; D012131:Respiratory Insufficiency / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha