Rapid Onset of Specific Diaphragm Weakness in a Healthy Murine Model of Ventilator-induced Diaphragmatic Dysfunction

Mrozek, Ségolène; Jung, Boris; Petrof, Basil J.; Pauly, Marion; Roberge, Stéphanie; Lacampagne, Alain; Cassan, Cécile; Thireau, Jérôme; Molinari, Nicolas; Futier, Emmanuel; Scheuermann, Valérie; Constantin, Jean Michel; Matecki, Stéfan; Jaber, Samir

doi:10.1097/aln.0b013e318261e7f8

Cited by 60 publications

(64 citation statements)

References 43 publications

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“…They obtained biopsy specimens from diaphragm muscle in brain-dead organ donors who had complete diaphragmatic inactivity and MV for 18 - 69 hours, and reported marked atrophy of diaphragm muscle fibers, consistent with the findings of previous animal studies [12]. Significant atrophy of diaphragm muscle fibers after prolonged MV has been reported in various species, including mice, rats, rabbits, and pigs [13][14][15][16]. Mrozek et al [15] recently reported VIDD in a mouse model in which 6 hours of MV resulted in significant reduction of diaphragmatic specific force [15].…”

Section: Discussionsupporting

confidence: 66%

“…Significant atrophy of diaphragm muscle fibers after prolonged MV has been reported in various species, including mice, rats, rabbits, and pigs [13][14][15][16]. Mrozek et al [15] recently reported VIDD in a mouse model in which 6 hours of MV resulted in significant reduction of diaphragmatic specific force [15]. However, they did not show any histological findings of atrophy, in contrast to several other animal and human studies [12,14,17,18].…”

Section: Discussionmentioning

confidence: 55%

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Effects of Lower Tidal Volume on Ventilator-Induced Diaphragmatic Dysfunction

DH¹

2017

JLPRR

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Purpose: Mechanical ventilation (MV) is one of the most important treatment to achieve sufficient alveolar ventilation in patients with lack of adequate pulmonary gas exchange. This study was performed to evaluate the effects of tidal volume ventilation to diaphragmatic dysfunction by both histological evaluation and the main protease pathway after MV with a murine ventilator induced diaphragmatic dysfunction (VIDD) model. Materials and Methods:Healthy male C57/BL6 mice (10 - 12 weeks old, 25 - 30 g) were randomly divided into 3 experimental groups: high tidal volume MV for 6 hours (HTV group, n = 6), low tidal volume MV for 6 hours (LTV group, n = 6), and control (Control group, n = 6). Arterial blood gas analysis, examination of diaphragmatic contractile properties, histological evaluation, and biochemical evaluation of main proteolysis pathways were performed in all three groups. Results:The results of arterial blood gas analysis were comparable among the three groups and all of them were within the normal ranges. Diaphragmatic force production was lower in the HTV group compared to the LTV and control group, respectively. Diaphragmatic force production in the LTV group was higher than that in the HTV group but only slightly reduced compared to the control group. There were no histological differences were found between the groups. No alterations in the level of calpain 1 or 2 were observed among the group, respectively. Conclusion:Lower tidal volume ventilation partially reduces ventilator-induced diaphragmatic dysfunction. Further studies are needed to determine the mechanism.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 55%

Effects of Lower Tidal Volume on Ventilator-Induced Diaphragmatic Dysfunction

DH¹

2017

JLPRR

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“…Indeed, numerous animal studies consistently report that prolonged MV results in a rapid and time-dependent decrease in diaphragmatic specific force production measured in vitro using electrical stimulation of diaphragmatic muscle strips (9,16,19,33,35,56,87,93,98). A recent report suggests that as few as 6 h of MV results in diaphragmatic contractile dysfunction in mice (73). In a rat model of MV, 12 h of full ventilator support results in a ϳ15-20% reduction in maximal diaphragmaticspecific force production, whereas 48 h of MV can depress diaphragm maximal specific force by ϳ50% below the level of control animals (56,87) (Fig.…”

Section: Mv-induced Diaphragmatic Contractile Dysfunctionmentioning

confidence: 99%

“…Numerous animal studies using a variety of species (mice, rats, rabbits, and pigs) have reported that prolonged MV results in significant atrophy of diaphragm muscle fibers (16,49,73,78,100,107). However, because the rat and human diaphragm are anatomically alike and contain a similar fiber type composition (76,81), the rat has become the most commonly used animal model to study MV-induced changes in diaphragm fiber size and function.…”

Section: Mv-induced Diaphragm Atrophymentioning

confidence: 99%

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Ventilator-induced diaphragm dysfunction: cause and effect

Powers

Wiggs

Sollanek

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

136

156

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Powers SK, Wiggs MP, Sollanek KJ, Smuder AJ. Ventilator-induced diaphragm dysfunction: cause and effect. Am J Physiol Regul Integr Comp Physiol 305: R464 -R477, 2013. First published July 10, 2013 doi:10.1152/ajpregu.00231.2013 is used clinically to maintain gas exchange in patients that require assistance in maintaining adequate alveolar ventilation. Common indications for MV include respiratory failure, heart failure, drug overdose, and surgery. Although MV can be a life-saving intervention for patients suffering from respiratory failure, prolonged MV can promote diaphragmatic atrophy and contractile dysfunction, which is referred to as ventilator-induced diaphragm dysfunction (VIDD). This is significant because VIDD is thought to contribute to problems in weaning patients from the ventilator. Extended time on the ventilator increases health care costs and greatly increases patient morbidity and mortality. Research reveals that only 18 -24 h of MV is sufficient to develop VIDD in both laboratory animals and humans. Studies using animal models reveal that MV-induced diaphragmatic atrophy occurs due to increased diaphragmatic protein breakdown and decreased protein synthesis. Recent investigations have identified calpain, caspase-3, autophagy, and the ubiquitin-proteasome system as key proteases that participate in MV-induced diaphragmatic proteolysis. The challenge for the future is to define the MV-induced signaling pathways that promote the loss of diaphragm protein and depress diaphragm contractility. Indeed, forthcoming studies that delineate the signaling mechanisms responsible for VIDD will provide the knowledge necessary for the development of a pharmacological approach that can prevent VIDD and reduce the incidence of weaning problems. respiratory muscle; atrophy; mechanical ventilation; weaning; muscle wasting MECHANICAL VENTILATION (MV) is used clinically to achieve sufficient pulmonary gas exchange in patients unable to sustain adequate alveolar ventilation on their own. Common indications for MV include respiratory failure due to chronic obstructive pulmonary disease, status asthmaticus, and/or heart failure. In addition, MV is often an essential intervention in patients suffering from acute drug overdose, neuromuscular diseases, sepsis, and during surgery along with postsurgical recovery.The number of patients receiving prolonged MV in the United States exceeds more than 300,000 each year in the intensive care unit (ICU) (20). Although MV can be a lifesaving measure, prolonged MV results in the rapid development of diaphragmatic weakness due to both atrophy and contractile dysfunction. This detrimental impact of prolonged MV on the diaphragm has been termed ventilator-induced diaphragmatic dysfunction (VIDD) and VIDD is predicted to be a major contributor to problems in weaning patients from the ventilator (26, 114). Although previous reports describing the impact of prolonged MV on the diaphragm have appeared in the literature, advances in our understanding of the mechanisms responsible for VIDD h...

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Dysfunction of respiratory muscles in critically ill patients on the intensive care unit

Berger

Bloechlinger

Haehling

et al. 2016

J cachexia sarcopenia muscle

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Muscular weakness and muscle wasting may often be observed in critically ill patients on intensive care units (ICUs) and may present as failure to wean from mechanical ventilation. Importantly, mounting data demonstrate that mechanical ventilation itself may induce progressive dysfunction of the main respiratory muscle, i.e. the diaphragm. The respective condition was termed ‘ventilator‐induced diaphragmatic dysfunction’ (VIDD) and should be distinguished from peripheral muscular weakness as observed in ‘ICU‐acquired weakness (ICU‐AW)’.Interestingly, VIDD and ICU‐AW may often be observed in critically ill patients with, e.g. severe sepsis or septic shock, and recent data demonstrate that the pathophysiology of these conditions may overlap. VIDD may mainly be characterized on a histopathological level as disuse muscular atrophy, and data demonstrate increased proteolysis and decreased protein synthesis as important underlying pathomechanisms. However, atrophy alone does not explain the observed loss of muscular force. When, e.g. isolated muscle strips are examined and force is normalized for cross‐sectional fibre area, the loss is disproportionally larger than would be expected by atrophy alone. Nevertheless, although the exact molecular pathways for the induction of proteolytic systems remain incompletely understood, data now suggest that VIDD may also be triggered by mechanisms including decreased diaphragmatic blood flow or increased oxidative stress. Here we provide a concise review on the available literature on respiratory muscle weakness and VIDD in the critically ill. Potential underlying pathomechanisms will be discussed before the background of current diagnostic options. Furthermore, we will elucidate and speculate on potential novel future therapeutic avenues.

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Rapid Onset of Specific Diaphragm Weakness in a Healthy Murine Model of Ventilator-induced Diaphragmatic Dysfunction

Abstract: Controlled mechanical ventilation for 6 h in the mouse is associated with significant diaphragmatic but not limb muscle weakness without atrophy or sarcolemmal injury and activates proteolysis.

Cited by 60 publications

References 43 publications

Effects of Lower Tidal Volume on Ventilator-Induced Diaphragmatic Dysfunction

Effects of Lower Tidal Volume on Ventilator-Induced Diaphragmatic Dysfunction

Ventilator-induced diaphragm dysfunction: cause and effect

Dysfunction of respiratory muscles in critically ill patients on the intensive care unit

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