Recovery of diaphragm function following mechanical ventilation in a rodent model.
BACKGROUND
Mechanical ventilation (MV) induces diaphragmatic muscle fiber atrophy and contractile dysfunction (ventilator induced diaphragmatic dysfunction, VIDD). It is unknown how rapidly diaphragm muscle recovers from VIDD once spontaneous breathing is restored. We hypothesized that following extubation, the return to voluntary breathing would restore diaphragm muscle fiber size and contractile function using an established rodent model.


METHODS
Following 12 hours of MV, animals were either euthanized or, after full wake up, extubated and returned to voluntary breathing for 12 hours or 24 hours. Acutely euthanized animals served as controls (each n = 8/group). Diaphragmatic contractility, fiber size, protease activation, and biomarkers of oxidative damage in the diaphragm were assessed.


RESULTS
12 hours of MV induced VIDD. Compared to controls diaphragm contractility remained significantly depressed at 12 h after extubation but rebounded at 24 h to near control levels. Diaphragmatic levels of oxidized proteins were significantly elevated after MV (p = 0.002) and normalized at 24 hours after extubation.


CONCLUSIONS
These findings indicate that diaphragm recovery from VIDD, as indexed by fiber size and contractile properties, returns to near control levels within 24 hours after returning to spontaneous breathing. Besides the down-regulation of proteolytic pathways and oxidative stress at 24 hours after extubation further repairing mechanisms have to be determined.
Department of Surgical Intensive and Intermediate Care, and Department of Anesthesiology, University hospital of the RWTH Aachen, University of Excellence, Aachen, Germany.
Christian S
CS
Bruells
Department of Surgical Intensive and Intermediate Care, and Department of Anesthesiology, University hospital of the RWTH Aachen, University of Excellence, Aachen, Germany.
Ingmar
I
Bergs
Department of Surgical Intensive and Intermediate Care, and Department of Anesthesiology, University hospital of the RWTH Aachen, University of Excellence, Aachen, Germany.
Rolf
R
Rossaint
Department of Surgical Intensive and Intermediate Care, and Department of Anesthesiology, University hospital of the RWTH Aachen, University of Excellence, Aachen, Germany.
Jun
J
Du
Department of Surgical Intensive and Intermediate Care, and Department of Anesthesiology, University hospital of the RWTH Aachen, University of Excellence, Aachen, Germany.
Christian
C
Bleilevens
Department of cardiothoracic and vascular surgery, University hospital of the RWTH Aachen, University of Excellence, Aachen, Germany.
Andreas
A
Goetzenich
Institute of Neuropathology and JARA - Translational Brain Medicine, University hospital of the RWTH Aachen, University of Excellence, Aachen, Germany.
Joachim
J
Weis
Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, United States of America.
Michael P
MP
Wiggs
Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, United States of America.
Scott K
SK
Powers
Department of Surgical Intensive and Intermediate Care, and Department of Anesthesiology, University hospital of the RWTH Aachen, University of Excellence, Aachen, Germany.
Marc
M
Hein
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D003964:Diaphragm / Q000473:pathology / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D051381:Rats; D020127:Recovery of Function / Q000502:physiology*; D012121:Respiration, Artificial / Q000009:adverse effects*; D015656:Respiratory Mechanics / Q000502:physiology*; D013997:Time Factors