P559Altered cardiac mitochondrial function in experimental uraemia

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Chronic Kidney Disease results in an increased risk of cardiac events through enhanced susceptibility to ischaemia-reperfusion (IR) injury, although the mechanisms are unclear. The aim of this study was to characterize cardiac mitochondrial function and susceptibility to stress in a model of uraemic cardiomyopathy.


Experimental uraemia (U) was induced in Sprague-Dawley rats via subtotal nephrectomy. Mitochondria were isolated at 12 weeks and respiratory rates were determined alongside calcium-induced swelling which was monitored spectrophotmetrically. Mitochondrial enzyme activities were determined in submitochondrial particles.


Urinary creatinine clearance was significantly impaired (0.78 ± 0.1(U) vs. 1.31 ± 0.1ml/min (Con), P < 0.01) and left ventricular hypertrophy evident in uraemic hearts (Heart Wt:Tibia Length - 0.46 ± 0.01 vs. 0.41 ± 0.01 g/cm, P < 0.01). State 4 respiratory rates were significantly increased in uraemia in the presence of complex I and complex II-linked substrates (CI - 46 ± 3 vs. 32 ± 3; CII - 94 ± 5 vs. 77 ± 5 nA Oxygen/min/mg protein,) while state 3 respiration rates were unchanged. Rates of calcium-induced swelling were significantly increased in mitochondria isolated from U hearts.


These results demonstrate that uraemic cardiac mitochondria exhibit decreased respiratory coupling and enhanced calcium-induced permeability transition, which may predispose the uraemic heart to a greater susceptibility to calcium-induced cell death.

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