Ventilator-induced Diaphgmatic Injury

Because controlled mechanical ventilation induces profound diaphragm muscle dysfunction and atrophy, Sassoon and colleagues tested the hypothesis that assisted mechanical ventilation will preserve diaphragmatic force and isotonic centractile properties and prevent overexpression of muscle atrophy factor-box (MAF-box). Studying sedated rabbits randomized equally into control animals, those with 3 days of assisted ventilation and those with controlled ventilation, they assessed in vitro diaphragmatic isometric and isotonic contractile function. The concentrations of contractile proteins, myosin heavy-chain isoform, and MAF-box mRNA were measured. Tetanic force decreased by 14% with assisted ventilation and 48% with controlled ventilation. Maximum shortening velocity tended to increase with controlled compared with assisted ventilation and control. Peak power output decreased 20% with assisted ventilation and 41% with controlled ventilation. Contractile proteins were unchanged with either mode of ventilation; myosin heavy-chain 2X mRNA tended to increase and that of 2A tended to decrease with controlled ventilation. The MAF-box gene was overexpressed with controlled ventilation. The authors concluded that preserving diaphragmatic contractions during mechanical ventilation attenuates the force loss induced by complete inactivity and maintains MAF-box gene expression in the control range.

In a critical care perspective, Vassilakopoulos and Petrof reviewed the evidence for ventilator-induced diaphragmatic dysfunction together with a discussion of the cellular changes that occur in the diaphragm in this condition and the known effects of other forms of skeletal muscle disuse.

To determine the role of antioxidants in diaphragmatic contractile dysfunction produced by prolonged ventilation, Betters and coworkers placed rats on mechanical ventilation for 12 hours with and without 20 mg/kg of Trolox, 6-hydroxy-2,5,7,8-tetramethylchoroman-2-carboxylic acid). Their mechanical ventilation protocol resulted in a 17% reduction in maximal tetanic force production. Trolox attenuated the loss of maximal force generation as well as the increase in the chymotrypsin-like activity of the 20S proteasome that resulted from mechanical ventilation. The authors concluded that oxidative damage induced by prolonged mechanical ventilation is accompanied by diaphragmatic dysfunction with protein degradation and that Trolox blocks this contractile defect.

Prolonged mechanical ventilation results in diaphragmatic atrophy and contractile dysfunction, but its effect on the rate of protein synthesis is not known. To investigate this issue, Shanely and coworkers studied rats receiving mechanical ventilation and measured diaphragmatic protein synthesis in vivo. The fractional rate of protein synthesis was computed as the magnitude of (¹³C)leucine enrichment in proteins divided by the enrichment of (¹³C)leucine in the precursor pool. After 6 hours of mechanical ventilation, the decrease in diaphragmatic protein synthesis reached 30% for mixed muscle protein and 65% for myosin heavy-chain protein. These decreases persisted for 18 hours. Real-time polymerase chain reaction analyses showed unchanged diaphragmatic levels of type I and IIx myosin heavy-chain mRNA levels during mechanical ventilation. The authors concluded that mechanical ventilation decreases the rate of protein synthesis in the diaphragm by impairment of post-transcriptional events.

In rats, Racz and coworkers studied the effects of 24 hours of mechanical ventilation on muscle protein and transcription factors at the levels of both messenger RNA and protein. The diaphragm of ventilated rats exhibited decreases in messenger RNA of MyoD, myosin heavy chain-2a and -2b, and sarcoplasmic/endoplasmic reticulum calcium–ATPase-1a; messenger RNA of myogenin was increased. Protein expression of MyoD and myogenin followed the changes in messenger RNA; isoforms of myosin heavy chains did not change. Parallel experiments on the gastrocnemius revealed that immobilization induced deconditioning; passive shortening induced no additional effects. The two muscles exhibited a similar pattern of change with the exception of protein expression of MyoD, which increased in the gastrocnemius and decreased in the diaphragm (messenger RNA decreased in both muscles). The authors conclude that controlled mechanical ventilation alters the levels of messenger RNA for muscle heavy chain isoforms and sarcoplasmic/endoplasmic reticulum calcium–ATPase isoforms within 24 hours.

In a state of the art review article, Laghi and Tobin discuss disorders of the respiratory muscles.

Citations 1-6 of 6 total displayed.

Trolox Attenuates Mechanical Ventilation–induced Diaphragmatic Dysfunction and Proteolysis

Jenna L. Betters, David S. Criswell, R. Andrew Shanely, Darin Van Gammeren, Darin Falk, Keith C. DeRuisseau, Melissa Deering, Tossaporn Yimlamai, and Scott K. Powers
Am. J. Respir. Crit. Care Med. 170: 1179 -1184. First published online as doi:10.1164/rccm.200407-939OC [Abstract] [Full text]

Mechanical Ventilation Depresses Protein Synthesis in the Rat Diaphragm

R. Andrew Shanely, Darin Van Gammeren, Keith C. DeRuisseau, A. Murat Zergeroglu, Michael J. McKenzie, Kevin E. Yarasheski, and Scott K. Powers
Am. J. Respir. Crit. Care Med. 170: 994 -999. First published online as doi:10.1164/rccm.200304-575OC [Abstract] [Full text]

Assist–Control Mechanical Ventilation Attenuates Ventilator-induced Diaphragmatic Dysfunction

Catherine S. H. Sassoon, Ercheng Zhu, and Vincent J. Caiozzo
Am. J. Respir. Crit. Care Med. 170: 626 -632. First published online as doi:10.1164/rccm.200401-042OC [Abstract] [Full text]

Ventilator-induced Diaphragmatic Dysfunction

Theodoros Vassilakopoulos and Basil J. Petrof
Am. J. Respir. Crit. Care Med. 169: 336-341. [Full text]

Early Changes in Rat Diaphragm Biology with Mechanical Ventilation

Gábor Z. Rácz, Ghislaine Gayan-Ramirez, Dries Testelmans, Pascal Cadot, Kristel De Paepe, Erno Zádor, Frank Wuytack, and Marc Decramer
Am. J. Respir. Crit. Care Med. 168: 297 -304. First published online as doi:10.1164/rccm.200206-541OC [Abstract] [Full text]

Disorders of the Respiratory Muscles

Franco Laghi and Martin J. Tobin
Am. J. Respir. Crit. Care Med. 168: 10-48. [Abstract] [Full text]

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