Prolonged controlled mechanical ventilation in humans triggers myofibrillar contractile dysfunction and myofilament protein loss in the diaphragm

Abstract

Prolonged CMV in humans triggers significant decreases in active and passive diaphragm myofibrillar force generation. This response is mediated, in part, by impaired myosin cross-bridge kinetics and decreased myofibrillar protein levels.

Intraoperative hemidiaphragm electrical stimulation reduces oxidative stress and upregulates autophagy in surgery patients undergoing mechanical ventilation: exploratory study

“…Moreover, high levels of oxidative stress and autophagy were linked to apoptotic and proteolytic processes that had consequences in diaphragm dysfunction and developed VIDD in mechanically ventilated patients [2, 21]. However, recent reports suggest that physiological levels of ROS formation and autophagy are essential for cellular signaling and homeostasis [22].…”

“…However, other studies reported a link between higher levels of autophagy and human diaphragm atrophy in mechanically ventilated patients [21]. For examples, Hussain et al reported higher levels of oxidative stress (4-HNE expression) and upregulated autophagy levels (LC3-II/I ratio) and evidence of autophagosome formation in chronically ventilated patients (average MV time 59 ± 16.5 h) in comparison with a control group (2–4 h of MV) [2, 21]. Also, animal studies have shown that diaphragm function preservation was accompanied by lower levels of oxidative stress and autophagy [20].…”

“…However, diaphragmatic unloading induced by MV may result in deleterious changes on the cellular level even within the first few hours from the intubation [1]. Diaphragm unloading may contribute to diaphragm muscle dysfunction that impairs weaning and can lead to the ventilator- induced diaphragm dysfunction (VIDD) [2]. Studies have shown that the intermittent intraoperative hemidiaphragm electrical stimulation may maintain or improve post-surgery diaphragm function [3–6].…”

Ventilator-induced diaphragmatic dysfunction

“…With respect to muscle contractility, one study found no changes in the force generated by permeabilized diaphragm fibers from brain-dead organ donor patients after an average mechanical ventilation period of 26 h [20]. However, another recent study with a longer (49 h) average period of mechanical ventilation reported decreased active as well as passive force production by isolated diaphragm myofibrils [21].…”

Respiratory muscle wasting in the ICU: is it time to protect the diaphragm?

“…Hussain and colleagues provide us with this important missing proof-of-concept information on the effects of VIDD on diaphragmatic contractility in humans and explore underlying mechanisms 15. These investigators obtained diaphragm biopsies from 13 subjects undergoing cardiac surgery (control group) and 12 brain-dead organ donors (CMV group).…”