title: Time course of diaphragm function recovery after controlled mechanical ventilation in rats.
abstract: Controlled mechanical ventilation (CMV) is known to result in rapid and severe diaphragmatic dysfunction, but the recovery response of the diaphragm to normal function after CMV is unknown. Therefore, we examined the time course of diaphragm function recovery in an animal model of CMV. Healthy rats were submitted to CMV for 24-27 h (n = 16), or to 24-h CMV followed by either 1 h (CMV + 1 h SB, n = 9), 2 h (CMV + 2 h SB, n = 9), 3 h (CMV + 3 h SB, n = 9), or 4-7 h (CMV + 4-7 h SB, n = 9) of spontaneous breathing (SB). At the end of the experiment, the diaphragm muscle was excised for functional and biochemical analysis. The in vitro diaphragm force was significantly improved in the CMV + 3 h SB and CMV + 4-7 h SB groups compared with CMV (maximal tetanic force: +27%, P < 0.05, and +59%, P < 0.001, respectively). This was associated with an increase in the type IIx/b fiber dimensions (P < 0.05). Neutrophil influx was increased in the CMV + 4-7 h SB group (P < 0.05), while macrophage numbers remained unchanged. Markers of protein synthesis (phosphorylated Akt and eukaryotic initiation factor 4E binding protein 1) were significantly increased (±40%, P < 0.001, and ±52%, P < 0.01, respectively) in the CMV + 3 h SB and CMV + 4-7 h SB groups and were positively correlated with diaphragm force (P < 0.05). Finally, also the maximal specific force generation of skinned single diaphragm fibers was increased in the CMV + 4-7 h SB group compared with CMV (+45%, P < 0.05). In rats, reloading the diaphragm for 3 h after CMV is sufficient to improve diaphragm function, while complete recovery occurs after longer periods of reloading. Enhanced muscle fiber dimensions, increased protein synthesis, and improved intrinsic contractile properties of diaphragm muscle fibers may have contributed to diaphragm function recovery.
authors.affiliation: Respiratory Muscle Research Unit, Laboratory of Pneumology and Respiratory Division, Katholieke Universiteit Leuven, Leuven, Belgium;
authors.forename: Debby
authors.initials: D
authors.lastname: Thomas
authors.forename: Karen
authors.initials: K
authors.lastname: Maes
authors.forename: Anouk
authors.initials: A
authors.lastname: Agten
authors.forename: Leo
authors.initials: L
authors.lastname: Heunks
authors.forename: Richard
authors.initials: R
authors.lastname: Dekhuijzen
authors.forename: Marc
authors.initials: M
authors.lastname: Decramer
authors.forename: Hieronymus
authors.initials: H
authors.lastname: Van Hees
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Gayan-Ramirez
mesh_terms: D000818:Animals; D002154:Calpain / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis; D053148:Caspase 3 / Q000378:metabolism; D003964:Diaphragm / Q000473:pathology / Q000503:physiopathology*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D023421:Models, Animal; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000473:pathology / Q000502:physiology; D009124:Muscle Proteins / Q000096:biosynthesis; D009133:Muscular Atrophy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D009504:Neutrophils / Q000473:pathology; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000096:biosynthesis; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology; D012121:Respiration, Artificial / Q000009:adverse effects*; D013997:Time Factors; D015300:Ventilator Weaning
chemical_list: D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; D051057:Proto-Oncogene Proteins c-akt; D002154:Calpain; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: controlled mechanical ventilation; diaphragm contractile properties; inflammation; protein synthesis; reloading