title: Enhanced generation of reactive oxygen species in the limb skeletal muscles from a murine infarct model of heart failure.
abstract: BACKGROUND
  The generation of reactive oxygen species (ROS) is enhanced in the failing myocardium. We hypothesized that ROS were also increased in the limb skeletal muscles in heart failure. Methods and Results-- Myocardial infarction (MI) was created in mice by ligating the left coronary artery. After 4 weeks, the left ventricle was dilated and contractility was diminished by echocardiography. Left ventricular end-diastolic pressure was elevated after MI in association with an increase in lung weight/body weight and the presence of pleural effusion. The generation of ROS in the limb muscles, including the soleus and gastrocnemius muscles, which were excised after MI, was measured by electron spin resonance spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (hydroxy-TEMPO). Overall, generation was increased, but it was attenuated in the presence of dimethylthiourea or 4,5-dihydroxy-1,2-benzenedisulfonic disodium salt in the reaction mixture, indicating increased generation of hydroxyl radicals originating from superoxide anion. Thiobarbituric acid-reactive substance formation was also increased in muscles after MI. Mitochondrial complex I and III activities were both decreased after MI, which may have caused the functional uncoupling of the respiratory chain and ROS production. Antioxidant enzyme activities, including superoxide dismutase, catalase, and glutathione peroxidase, were comparable between groups.
  
  
  CONCLUSIONS
  Skeletal muscle in post-MI heart failure expressed an increased amount of ROS in association with ROS-mediated lipid peroxidation. This supports the hypothesis that oxidative stress may cause (at least in part) skeletal muscle dysfunction in heart failure.
authors.affiliation: Departments of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. prehiro@cardiol.med.kyushu-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Tsutsui
authors.forename: T
authors.initials: T
authors.lastname: Ide
authors.forename: S
authors.initials: S
authors.lastname: Hayashidani
authors.forename: N
authors.initials: N
authors.lastname: Suematsu
authors.forename: T
authors.initials: T
authors.lastname: Shiomi
authors.forename: J
authors.initials: J
authors.lastname: Wen
authors.lastname: Nakamura Ki
authors.forename: K
authors.initials: K
authors.lastname: Ichikawa
authors.forename: H
authors.initials: H
authors.lastname: Utsumi
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D004452:Echocardiography; D004562:Electrocardiography; D004578:Electron Spin Resonance Spectroscopy; D017079:Exercise Tolerance; D005979:Glutathione Peroxidase / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D006439:Hemodynamics; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism*; D009929:Organ Size; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000209:etiology
chemical_list: D017382:Reactive Oxygen Species; D013113:Spin Labels; D017392:Thiobarbituric Acid Reactive Substances; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase