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MITOCHONDRIAL DYSFUNCTION AND OXIDATIVE STRESS IN URAEMIC CARDIOMYOPATHY
  1. F Nuhu1,
  2. T Mace*,2,
  3. R Sturmey1,
  4. S Bhandari2,
  5. AML Seymour1
  1. 1School of Biological, Biomedical and Environmental Sciences, University of Hull
  2. 2Department of Renal Medicine, Hull and East Yorkshire NHS Hospital Trust

Abstract

Patients with chronic kidney disease (CKD) have greater morbidity and mortality from cardiac causes with a defined uraemic cardiomyopathy (UCM). There is growing evidence that oxidative stress and mitochondrial dysfunction are important in the development and progression of heart failure (HF). The aim of this study is to investigate the role of mitochondrial dysfunction and oxidative stress in experimental UCM.

Experimental uraemia was induced in male Sprague-Dawley rats via a subtotal nephrectomy. Uraemia was characterised after 12 week by the measurement of serum creatinine and urea. The degree of cardiac hypertrophy was determined by heart weight to tibia length ratio (HW/TL). Respiration rates were measured in isolated cardiac mitochondria, total mitochondrial cardiolipin (CL) content and its constituent side chains were determined by GCMS and oxidative stress assessed from levels of thiobarbituric acid-reactive substances (TBARS) and glutathione (reduced (GSH) and oxidised (GSSG).

Renal impairment was evident by increased serum creatinine (uraemia: 96.46±14.86 µM vs control: 44.96±2.69 µM, p<0.01). HW/TL was significantly enhanced indicating substantial cardiac hypertrophy. State 3 respiration in uraemic mitochondria was increased in parallel with enhanced CL remodelling and content. Evidence of oxidative stress in UCM was demonstrated by elevated TBARS levels (0.73±0.37 vs 1.40±0.22 ρmol/mg protein p<0.05) and GSSG/GSH ratio (0.098±0.002 vs 0.052±0.002, p<0.01).

These findings indicate evidence of mitochondrial remodelling and increased oxidative stress at this stage in UCM, which may underpin the enhanced susceptibility to ischaemic injury.

  • CARDIAC PROCEDURES AND THERAPY

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