Rationale:Mechanical ventilation is associated with diaphragm dysfunction and systemic inflammation. Whether inflammation is involved in ventilator−induced diaphragm dysfunction is largely unknown. Activation of toll like receptor−4 (TLR−4) activates intracellular inflammatory cascades. Aim: To investigate the role of toll like receptor 4 (TLR−4) signaling in the development of ventilator−induced diaphragm dysfunction. Methods: Wild type (WT, n = 4) and TLR−4 knock−out (TLR4−KO, n = 4) mice were mechanically ventilated for 8 hours (tidal volume 8 ml/kg; PEEP 1,5 cm H20; respiratory rate 170/min). Immediately after sacrifice diaphragm muscle bundles were dissected. From these bundles chemically skinned diaphragm fibers were isolated. Absolute maximal force generation was determined upon calcium activation (pCa 4.5). Results: Pao2 / Fio2 ratio were not significantly different between WT and TLR4−KO mice after 8 hours of mechanical ventilation (492 ± 40 and 531 ± 45 respectively). Absolute maximal force generation of diaphragm fibers from TLR4 KO mice was 15% higher compared to WT mice (2,34 ± 0.32 mg vs. 2,04 ± 0.13 mg respectively).
Conclusion:The present study demonstrates that TLR−4 signaling is involved in the development of ventilator−induced diaphragm dysfunction. TLR−4 signaling did not affect pulmonary function in mechanically ventilated mice. This abstract is funded by: None. Am J Respir Crit Care Med 179;2009:A4196 Internet address: www.atsjournals.org Online Abstracts Issue
Corresponding author's email: J.Hannink@elg.umcn.nlPatients with COPD report more dyspnea during arm than during leg exercise. One of the major causes of dyspnea is dynamic Purpose: hyperinflation (DH), which is caused by airflow limitation as well as increase in ventilation. The aim of our study was to compare DH at equal ventilation (isoventilation) during arm and leg work and to investigate the effects of breathing pattern on DH.: Thirteen clinically stable patients with mild-to-very severe COPD (FEV 59±6%) participated in this study. Arm and leg constant Methods 1 work rate (CWR) ergometry were performed in random order with ventilation equal to that at 50% of peak arm load. The corresponding leg load of that level of ventilation was determined from the incremental leg test. Respiratory physiology was measured breath-by-breath. Change in inspiratory capacity, measured at rest and at 2min intervals, was used to reflect DH.At steady state isoventilation (37±2 and 36±2L/min for arm and leg CWR tests respectively, p>0.05), arm load was 29±5Watt and Results: leg load 52±6Watt (p<0.001). The level of DH, 0.32±0.09 and 0.27±0.08L during arm and leg exercise respectively, was not significantly different ( Figure 1). However, breathing frequency was greater during arm than during leg exercise (24±1 versus 21±1breaths/min, p<0.01) (Figure 2) and the opposite was true for tidal volume (1.56±0.15 versus 1.69±0.14L, p<0.01).At similar ventilation, we found a similar degree of DH during arm and leg CWR tests in patients with mild-to-very severe Conclusion: COPD. Although differences in breathing pattern were observed between arm and leg exercise, these did not affect the level of DH. Figure 1. Inspiratory capacity during isoventilation leg and arm constant work rate ergometry.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.