title: Diaphragm contractile dysfunction causes by off-target low-dose irradiation.
abstract: BACKGROUND
  Diaphragm is a primary inspiratory muscle and often receives off-target dose in patients with thoracic radiotherapy, and whether acute effect of low dose irradiation would cause contractile dysfunction of the diaphragm remains unclear. We use a rat model to investigate the effect of low-dose irradiation on diaphragm contractile function in the current study.
  
  
  METHODS
  The radiation dose distributions in patients with esophageal cancer receiving radiotherapy were calculated to determine the dose received by the off-target diaphragm area. Rats were randomly assigned to an irradiated or a non-irradiated control group (n = 10 per group). A single-fraction of 5 Gy radiation was then delivered to the diaphragms of Sprague-Dawley rats in the irradiated group. The control group received sham irradiation (0 Gy). Rats were sacrificed 24 hours after the irradiation procedures and diaphragms were removed en bloc for contractile function assessment, oxidative injury and DNA damage analysis. Oxidative injury was determined by analyzing concentration of protein carbonyls and DNA damage was determined by analyzing retention of γH2AX foci in nuclei of diaphragmatic tissue.
  
  
  RESULTS
  At 24 hours after delivery of a single dose of 5 Gy radiation, specific twitch (p = 0.03) and tetanus tension (p = 0.02) were significantly lower in the irradiated group than in the control group. The relative force-frequency curves showed a significant downward shift in the irradiated group. Protein carbonyl level (p < 0.01) and percentage of γH2AX-positive diaphragm muscle cells were significantly higher in the irradiated group than in the control group 24 hours after irradiation (58% vs. 30%, p = 0.01).
  
  
  CONCLUSIONS
  Off-target low dose irradiation could induce acute contractile dysfunction of the diaphragm which was related to radiation-induced direct DNA and indirect oxidative damage.
authors.affiliation: Department of Radiation Oncology, Far Eastern Memorial HospitalTaipei, Taiwan; Department of Medicine, School of Medicine, National Yang-Ming UniversityTaipei, Taiwan; Institute of Traditional Medicine, School of Medicine, National Yang-Ming UniversityTaipei, Taiwan.
authors.forename: Chen-Hsi
authors.initials: CH
authors.lastname: Hsieh
authors.affiliation: School and Graduate Institute of Physical Therapy, College of Medicine, National Taiwan University Taiwan.
authors.forename: Yun-Cheng
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming UniversityTaipei, Taiwan; Department of Radiation Oncology, Mackay Memorial HospitalTaipei, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Integrated Diagnostic & Therapeutics, National Taiwan University Hospital Taipei, Taiwan.
authors.forename: Huey-Dong
authors.initials: HD
authors.lastname: Wu
authors.affiliation: School and Graduate Institute of Physical Therapy, College of Medicine, National Taiwan UniversityTaiwan; Physical Therapy Center, National Taiwan University HospitalTaipei, Taiwan.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Wang
keywords: Irradiation; oxidative stress; respiratory measurement; respiratory muscles