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INTERMITTENT SPONTANEOUS BREATHING PREVENTS MECHANICAL VENTILATION‐INDUCED DIAPHRAGM ATROPHY AND DYSFUNCTION
Author(s) -
IchinosekiSekine Noriko,
Yoshihara Toshinori,
Tsuzuki Takamasa,
Morton Aaron,
Hinkley Matthew J,
Powers Scott K,
Naito Hisashi
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb770
Subject(s) - medicine , diaphragm (acoustics) , mechanical ventilation , ventilation (architecture) , atrophy , spontaneous breathing trial , anesthesia , mechanical engineering , physics , acoustics , loudspeaker , engineering
Mechanical ventilation (MV) is used to provide adequate pulmonary ventilation for patients in respiratory failure. Although MV is often a life‐saving intervention, prolonged MV results in the rapid development of diaphragm atrophy and contractile dysfunction (collectively known as ventilator‐induced diaphragm dysfunction (VIDD)). Importantly, VIDD contributes to difficulty in weaning patients from MV, which is in turn associated with increased mortality and morbidity. Therefore, developing a strategy to protect the diaphragm against VIDD is important. Although studies have investigated the impact of prolonged MV on VIDD, limited data exist regarding the impact of intermittent spontaneous breathing during MV on protection against VIDD. Therefore, we investigated the effects of intermittent spontaneous breathing on VIDD. Adult male Wistar rats (n = ~10/group) were randomly assigned to one of three groups: 1) anesthetized control (CON) with no MV; 2) controlled MV (CMV) for 12 hours; and 3) intermittent spontaneous breathing during MV (1‐min spontaneous breathing phase per hour (IMV). In the IMV group, voluntary diaphragm activation occurred 89.2 ± 6.8 times during each minute of spontaneous breathing. As expected, CMV resulted in significant diaphragm atrophy and contractile dysfunction (P < 0.05) along with activation of caspase‐3 and phosphorylation of signal transducer/transcriptional activator‐3 (STAT3) in the diaphragm. In contrast, intermittent breathing prevented MV‐induced activation of caspase‐3 and phosphorylation of STAT3. Importantly, animals in the IMV group were protected against VIDD. These findings reveal that as little as 1‐min/hour of spontaneous breathing during MV is protective against VIDD, in part, by prevention of MV‐induced activation of caspase‐3 and STAT3 in the diaphragm. Support or Funding Information This work was supported by JSPS KAKENHI Grant Number 26350820 and 15KK0131 and NIH R01 , R01AR064189