title: Cardiac function and tolerance to ischemia-reperfusion injury in chronic kidney disease.
abstract: BACKGROUND
  Cardiac dysfunction is an independent risk factor of ischemic heart disease and mortality in chronic kidney disease (CKD) patients, yet the relationship between impaired cardiac function and tolerance to ischemia-reperfusion (IR) injury in experimental CKD remains unclear.
  
  
  METHODS
  Cardiac function was assessed in 5/6 ablation-infarction (AI) and sham male Sprague-Dawley rats at 20 weeks of age, 8 weeks post-surgery using an isolated working heart system. This included measures taken during manipulation of preload and afterload to produce left ventricular (LV) function curves as well as during reperfusion following a 15-min ischemic bout. In addition, LV tissue was used for biochemical tissue analysis.
  
  
  RESULTS
  Cardiac function was impaired in AI animals during preload and afterload manipulations. Cardiac functional impairments persisted post-ischemia in the AI animals, and 36% of AI animals did not recover sufficiently to achieve aortic overflow following ischemia (versus 0% of sham animals). However, for those animals able to withstand the ischemic perturbation, no difference was observed in percent recovery of post-ischemic cardiac function between groups. Urinary NOx (nitrite + nitrate) excretion was lower in AI animals and accompanied by reduced LV endothelial nitric oxide synthase and NOx. LV antioxidants superoxide dismutase-1 and -2 were reduced in AI animals, whereas glutathione peroxidase-1/2 as well as NADPH-oxidase-4 and H(2)O(2) were increased in these animals.
  
  
  CONCLUSIONS
  Impaired cardiac function appears to predispose AI rats to poor outcomes following short-duration ischemic insult. These findings could be, in part, mediated by increased oxidative stress via nitric oxide-dependent and -independent mechanisms.
authors.affiliation: Department of Kinesiology and Applied Physiology, University of Delaware, 25 N College Avenue, McDowell Hall, Newark, DE 19716, USA Department of Biological Sciences, University of Delaware, Newark, DE, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Kuczmarski
authors.affiliation: Department of Kinesiology and Applied Physiology, University of Delaware, 25 N College Avenue, McDowell Hall, Newark, DE 19716, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Martens
authors.affiliation: Department of Kinesiology and Applied Physiology, University of Delaware, 25 N College Avenue, McDowell Hall, Newark, DE 19716, USA Department of Behavioral Health and Nutrition, University of Delaware, Newark, DE, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Lennon-Edwards
authors.affiliation: Department of Kinesiology and Applied Physiology, University of Delaware, 25 N College Avenue, McDowell Hall, Newark, DE 19716, USA Department of Biological Sciences, University of Delaware, Newark, DE, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Edwards
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005919:Glomerular Filtration Rate; D006352:Heart Ventricles / Q000503:physiopathology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000503:physiopathology; D015427:Reperfusion Injury; D016276:Ventricular Function / Q000502:physiology*
keywords: cardiac dysfunction; cardiac ischemia–reperfusion injury; chronic kidney disease; nitric oxide; oxidative stress