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26 Changes in mitochondrial function in uraemic cardiomyopathy
  1. D Taylor1,
  2. S Bhandari2,
  3. A-M L Seymour1
  1. 1Department of Biological Sciences & Hull York Medical School, University of Hull, Kingston upon Hull, UK
  2. 2Hull York Medical School & Hull Royal Infirmary, Kingston upon Hull, UK

Abstract

Chronic kidney disease leads to cardiac dysfunction and ultimately heart failure, however the cellular mechanisms remain unclear. The aim of this study was to characterise cardiac mitochondrial function in an experimental model of uraemic cardiomyopathy (UCM). UCM was induced in Sprague-Dawley rats via subtotal nephrectomy. Mitochondria were isolated 12 weeks post surgery and respiratory rates determined, and calcium-induced swelling monitored spectrophotmetrically to investigate susceptibility to permeability transition. Mitochondrial complex and aconitase activities were measured in submitochondrial particles. Cardiac expression of uncoupling protein 3 (UCP3) was quantified by immunoblotting. Urinary creatinine clearance was significantly impaired (0.78±0.1 vs 1.31±0.1 ml/min Control, p<0.01) and left ventricular hypertrophy evident in UCM hearts (HW:TL—0.46±0.01 vs 0.41±0.01 g/cm, p<0.01). State 4 respiration was significantly increased in UCM mitochondria in the presence of complex I and complex II-linked substrates (CI—46±3 vs 32±3; CII—94±5 vs 77±5 nA O/min/mg protein, p<0.05) while state 3 respiration rates did not differ. Rates of calcium-induced swelling were significantly enhanced in UCM mitochondria, however, no differences were observed in complex activities, aconitase inactivation or UCP3 expression in UCM. These results demonstrate that cardiac mitochondria in UCM exhibit decreased respiratory coupling, although this is not associated with altered UCP3 expression. The observed enhancement in calcium-induced permeability transition may reflect an increased susceptibility to calcium-induced cell death.

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