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A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
Published on: November 7, 2017
Effects of carnitine supplementation on myocardial function and energy provision in experimental uraemia
Anne-Marie Seymour1, Veena Reddy, Sunil Bhandari
1Department of Biological Sciences and Hull York Medical School, University of Hull, Kingston-upon-Hull, United Kingdom.
Insights
Chronic kidney disease patients face heart issues. L-carnitine supplementation prevented cardiac hypertrophy in experimental uremia, reducing glucose use but not affecting heart function.
Area of Science:
- Nephrology
- Cardiology
- Biochemistry
Background:
- Cardiovascular complications are the primary cause of mortality in chronic kidney disease (CKD).
- Uremia induces cardiac remodeling, metabolic dysfunction, and reduced myocardial energy reserves.
- Experimental uremia is linked to left ventricular hypertrophy and carnitine depletion.
Purpose of the Study:
- To investigate the impact of chronic L-carnitine supplementation on myocardial substrate metabolism and cardiac function in experimental uremia.
- To determine if L-carnitine can mitigate the cardiac changes associated with uremia.
Main Methods:
- Experimental uremia was induced in Sprague-Dawley rats via subtotal nephrectomy.
- L-carnitine was administered continuously using mini-osmotic pumps.
- Cardiac function and substrate oxidation were assessed using in vitro isovolumic perfusion and 13C NMR at 3 and 6 weeks.
Main Results:
- Uremic animals showed anemia, kidney dysfunction, and systemic carnitine deficiency, but not myocardial carnitine deficiency.
- L-carnitine supplementation abolished myocardial hypertrophy in uremic rats.
- This effect was associated with reduced myocardial glucose utilization, and was amplified with treatment duration.
Conclusions:
- Chronic L-carnitine supplementation effectively prevents cardiac hypertrophy in experimental uremia.
- The cardioprotective effect of L-carnitine is linked to altered myocardial substrate utilization, specifically reduced glucose use.
- L-carnitine supplementation did not significantly alter myocardial function despite preventing hypertrophy.
Abstract:
Cardiovascular complications are the leading cause of death in patients with chronic kidney disease. The uraemic heart undergoes remodelling and changes in metabolic function. Experimental uraemia produces a reduction in the myocardial energy reserve phosphocreatine in parallel with left ventricular hypertrophy and depletion of serum carnitine. This study investigated the effects of chronic L-carnitine supplementation on myocardial substrate metabolism and function in the experimental uraemia. Experimental uraemia was induced surgically in male Sprague-Dawley rats via a subtotal nephrectomy. Carnitine was administered continuously via subcutaneous mini-osmotic pumps. Cardiac function and substrate oxidation were assessed in vitro by means of isovolumic perfusion using 13C NMR, at 3 and 6 weeks. Uraemic animals exhibited anaemia, kidney dysfunction and systemic carnitine deficiency but no myocardial tissue carnitine deficiency. Myocardial hypertrophy was abolished following carnitine supplementation. This was associated with a reduction in glucose utilisation. In summary carnitine supplementation prevents cardiac hypertrophy, and this effect is amplified with the duration of treatment. This is associated with a reduction in myocardial glucose utilisation but no significant modulation of myocardial function.
