Diaphragm Muscle Weakness in an Experimental Porcine Intensive Care Unit Model
Open Access
- 15 June 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (6), e20558
- https://doi.org/10.1371/journal.pone.0020558
Abstract
In critically ill patients, mechanisms underlying diaphragm muscle remodeling and resultant dysfunction contributing to weaning failure remain unclear. Ventilator-induced modifications as well as sepsis and administration of pharmacological agents such as corticosteroids and neuromuscular blocking agents may be involved. Thus, the objective of the present study was to examine how sepsis, systemic corticosteroid treatment (CS) and neuromuscular blocking agent administration (NMBA) aggravate ventilator-related diaphragm cell and molecular dysfunction in the intensive care unit. Piglets were exposed to different combinations of mechanical ventilation and sedation, endotoxin-induced sepsis, CS and NMBA for five days and compared with sham-operated control animals. On day 5, diaphragm muscle fibre structure (myosin heavy chain isoform proportion, cross-sectional area and contractile protein content) did not differ from controls in any of the mechanically ventilated animals. However, a decrease in single fibre maximal force normalized to cross-sectional area (specific force) was observed in all experimental piglets. Therefore, exposure to mechanical ventilation and sedation for five days has a key negative impact on diaphragm contractile function despite a preservation of muscle structure. Post-translational modifications of contractile proteins are forwarded as one probable underlying mechanism. Unexpectedly, sepsis, CS or NMBA have no significant additive effects, suggesting that mechanical ventilation and sedation are the triggering factors leading to diaphragm weakness in the intensive care unit.Keywords
This publication has 45 references indexed in Scilit:
- Neuromuscular adaptations to respiratory muscle inactivityRespiratory Physiology & Neurobiology, 2009
- Gene expression and muscle fiber function in a porcine ICU modelPhysiological Genomics, 2009
- Bench-to-bedside review: Diaphragm muscle function in disuse and acute high-dose corticosteroid treatmentCritical Care, 2009
- The Effects of Force Inhibition by Sodium Vanadate on Cross-Bridge Binding, Force Redevelopment, and Ca2+ Activation in Cardiac MuscleBiophysical Journal, 2007
- Rocuronium exacerbates mechanical ventilation–induced diaphragm dysfunction in ratsCritical Care Medicine, 2006
- A porcine model of acute quadriplegic myopathy: a feasibility studyActa Anaesthesiologica Scandinavica, 2006
- Myosin Loss in Denervated Rat Soleus Muscle after Dexamethasone TreatmentPathobiology, 2005
- Respiratory muscle fibres: specialisation and plasticityThorax, 2004
- Neuromuscular conditions in the intensive care unitIntensive Care Medicine, 1996
- Effects of Unilateral Phrenic Nerve Denervation on Diaphragm Contractility in Rat.The Tohoku Journal of Experimental Medicine, 1994