title: Intraoperative hemidiaphragm electrical stimulation reduces oxidative stress and upregulates autophagy in surgery patients undergoing mechanical ventilation: exploratory study.
abstract: Mechanical ventilation (MV) during a cardio-thoracic surgery contributes to diaphragm muscle dysfunction that impairs weaning and can lead to the ventilator- induced diaphragm dysfunction. Especially, it is critical in older adults who have lower muscle reparative capacity following MV. Reports have shown that the intraoperative intermittent hemidiaphragm electrical stimulation can maintain and/or improve post-surgery diaphragm function. In particular, from a molecular point of view, intermittent ES may reduce oxidative stress and increase regulatory autophagy levels, and therefore improve diaphragm function in animal studies. We have recently shown in humans that intraoperative ES attenuates mitochondrial dysfunction and force decline in single diaphragm muscle fibers. The aim of this study was to investigate an effect of ES on oxidative stress, antioxidant status and autophagy biomarker levels in the human diaphragm during surgery.
  
  
  
  One phrenic nerve was simulated with an external cardiac pacer in operated older subjects (62.4 ± 12.9 years) (n = 8) during the surgery. The patients received 30 pulses per min every 30 min. The muscle biopsy was collected from both hemidiaphragms and frozen for further analyses. 4-hydroxynonenal (4-HNE), an oxidative stress marker, and autophagy marker levels (Beclin-1 and the ratio of microtubule-associated protein light chain 3, I and II-LC3 II/I) protein concentrations were detected by the western blot technique. Antioxidant enzymatic activity copper-zinc (CuZnSOD) and manganese (MnSOD) superoxide dismutase were analyzed.
  
  
  
  Levels of lipid peroxidation (4-HNE) were significantly lower in the stimulated side (p < 0.05). The antioxidant enzyme activities (CuZnSOD and MnSOD) in the stimulated side of the diaphragm were not different than in the unstimulated side (p > 0.05). Additionally, the protein concentrations of Beclin-1 and the LC3 II/I ratio were higher in the stimulated side (p < 0.05).
  
  
  
  These results suggest that the intraoperative electrical stimulation decreases oxidative stress levels and upregulates autophagy levels in the stimulated hemidiaphragm. These results may contribute future studies and clinical applications on reducing post-operative diaphragm dysfunction.
authors: Department of Aging and Geriatric Research, University of Florida, P.O.Box. 100107, Gainesville, FL, 32611, USA.
authors: Robert T
authors: RT
authors: Mankowski
authors: Department of Physical Therapy, University of Florida, Box 100154, UFHSC, Gainesville, FL, 32610-0154, USA.
authors: Shakeel
authors: S
authors: Ahmed
authors: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Florida, Gainesville, FL, USA.
authors: Thomas
authors: T
authors: Beaver
authors: Department of Aging and Geriatric Research, University of Florida, P.O.Box. 100107, Gainesville, FL, 32611, USA.
authors: Marvin
authors: M
authors: Dirain
authors: Department of Aging and Geriatric Research, University of Florida, P.O.Box. 100107, Gainesville, FL, 32611, USA.
authors: Chul
authors: C
authors: Han
authors: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Florida, Gainesville, FL, USA.
authors: Phillip
authors: P
authors: Hess
authors: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Florida, Gainesville, FL, USA.
authors: Tomas
authors: T
authors: Martin
authors: Department of Physical Therapy, University of Florida, Box 100154, UFHSC, Gainesville, FL, 32610-0154, USA.
authors: Barbara K
authors: BK
authors: Smith
authors: Department of Aging and Geriatric Research, University of Florida, P.O.Box. 100107, Gainesville, FL, 32611, USA.
authors: Shinichi
authors: S
authors: Someya
authors: Department of Aging and Geriatric Research, University of Florida, P.O.Box. 100107, Gainesville, FL, 32611, USA. cleeuwen@ufl.edu.
authors: Christiaan
authors: C
authors: Leeuwenburgh
authors: Department of Physical Therapy, University of Florida, Box 100154, UFHSC, Gainesville, FL, 32610-0154, USA. DMartin@phhp.ufl.edu.
authors: A Daniel
authors: AD
authors: Martin
mesh_terms: D000368:Aged; D001343:Autophagy; D000071183:Autophagy-Related Proteins / Q000378:metabolism; D001706:Biopsy; D003710:Demography; D003964:Diaphragm / Q000473:pathology* / Q000601:surgery*; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D007430:Intraoperative Care; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012121:Respiration, Artificial; D015854:Up-Regulation
chemical_list: D000071183:Autophagy-Related Proteins