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Nephrol Dial Transplant. 2014 Aug;29(8):1514-24. doi: 10.1093/ndt/gft336. Epub 2013 Oct 22.

Cardiac function and tolerance to ischemia-reperfusion injury in chronic kidney disease.

Author information

  • 1Department 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.
  • 2Department of Kinesiology and Applied Physiology, University of Delaware, 25 N College Avenue, McDowell Hall, Newark, DE 19716, USA.
  • 3Department 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.

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.

© The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

KEYWORDS:

cardiac dysfunction; cardiac ischemia–reperfusion injury; chronic kidney disease; nitric oxide; oxidative stress

PMID:
24151020
[PubMed - indexed for MEDLINE]
PMCID:
PMC4106638
[Available on 2015/8/1]
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