Relationship between Autophagy and Ventilator-induced Diaphragmatic Dysfunction

Abstract

In this model of VIDD, autophagy is induced by MV but is not responsible for diaphragmatic weakness. The authors propose that autophagy may instead be a beneficial adaptive response that can potentially be exploited for therapy of VIDD.

Ventilator‐induced diaphragmatic dysfunction in MDX mice

“…In the present study we observed an upregulation of mRNA transcripts for LC3B and other autophagy‐associated genes in concert with reduced LC3B‐II protein levels in MV diaphragms. This constellation of changes is consistent with an accelerated rate of autophagosome formation and degradation, respectively (i.e., increased autophagic flux) . Interestingly, autophagy has been reported to be defective in mdx mouse muscles under basal conditions, whereas pharmacological activation of autophagy ameliorates dystrophic manifestations .…”

“…Interestingly, autophagy has been reported to be defective in mdx mouse muscles under basal conditions, whereas pharmacological activation of autophagy ameliorates dystrophic manifestations . Moreover, we have previously reported that stimulation of autophagy in non‐dystrophic mice is associated with prevention of diaphragmatic weakness during the early stages of VIDD . Therefore, activation of autophagy could potentially help to mitigate MV‐induced force loss in the dystrophic diaphragm, although this hypothesis requires formal testing in future studies.…”

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

“…Overall, this aspect of VIDD may open new therapeutic avenues as the redox state of a cell might theoretically be influenced positively . Recent data indicate protection from diaphragmatic weakness with N‐acetylcysteine via augmented autophagosome formation in mice …”

“…97 Currently, no medical treatment for VIDD is available. 126 Anti-oxidants show benefits in animal models 40,71,72,127 and in a randomized trial in critically ill surgical patients. 128 However, human data remain sparse.…”

“…71 Recent data indicate protection from diaphragmatic weakness with N-acetylcysteine via augmented autophagosome formation in mice. 72 Data from animal VIDD models demonstrate a quick and complete recovery within hours if spontaneous breathing is resumed early. However, this needs to be interpreted before the background of limited times of mechanical ventilation (12 to 27 h.).…”