title: Chronic intermittent hypobaric hypoxia attenuates radiation induced heart damage in rats.
abstract: OBJECTIVE
  Radiation-induced heart damage (RIHD) is becoming an increasing concern for patients and clinicians due to the use of radiotherapy for thoracic tumor. Chronic intermittent hypobaric hypoxia (CIHH) preconditioning has been documented to exert a cardioprotective effect. Here we hypothesized that CIHH was capable of attenuating functional and structural damage in a rat model of RIHD.
  
  
  METHODS
  Male adult Sprague-Dawley rats were randomly divided into 4 groups: control, radiation, CIHH and CIHH plus radiation. Cardiac function was measured using Langendorff perfusion in in vitro rat hearts. Cardiac fibrosis, oxidative stress and endoplasmic reticulum stress (ERS) was assessed by quantitative analysis of protein expression.
  
  
  RESULTS
  No significant difference between any two groups was observed in baseline cardiac function as assessed by left ventricular end diastolic pressure (LVEDP), left ventricular developing pressure (LVDP) and the derivative of left ventricular pressure (±LVdp/dt). When challenged by ischemia/reperfusion, LVEDP was increased but LVDP and ±LVdp/dt was decreased significantly in radiation group compared with controls, accompanied by an enlarged infarct size and decreased coronary flow. Importantly, CIHH dramatically improved radiation-induced damage of cardiac function and blunted radiation-induced cardiac fibrosis in the perivascular and interstitial area. Furthermore, CIHH abrogated radiation-induced increase in malondialdehyde and enhanced total superoxide dismutase activity, as well as downregulated expression levels of ERS markers like GRP78 and CHOP.
  
  
  CONCLUSIONS
  CIHH pretreatment alleviated radiation-induced damage of cardiac function and fibrosis. Such a protective effect was closely associated with suppression of oxidative stress and ERS responses.
authors.affiliation: Department of Radiation oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiation oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Yixian
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Radiation oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Radiation oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Cao
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang 050000, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang 050000, China. Electronic address: wangsheng@hebmu.edu.cn.
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D059865:Endoplasmic Reticulum Stress; D006321:Heart / Q000503:physiopathology / Q000528:radiation effects*; D006931:Hyperbaric Oxygenation; D008297:Male; D011832:Radiation Injuries / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
keywords: Chronic intermittent hypobaric hypoxia; Endoplasmic reticulum stress; Oxidative stress; Radiation induced heart damage