Value of carnitine therapy in kidney dialysis patients and effects on cardiac function from human and animal studies.
Cardiovascular complications are the leading cause of mortality, accounting for 50% of all deaths among patients with end-stage renal disease (ESRD). The majority of these deaths are from cardiac causes. The mechanisms underlying the enhanced susceptibility to myocardial ischaemia and subsequent morbidity in ESRD remain ill-defined. Numerous metabolic derangements accompany myocardial ischaemia and reperfusion and play a pivotal role in the development of concurrent myocardial dysfunction. Carnitine plays a critical role in myocardial energy metabolism, as the transporter of long chain fatty acyl intermediates across the inner mitochondrial membrane for β oxidation and as a central regulator of carbohydrate metabolism. Myocardial carnitine is significantly depleted during ischaemia and more particularly in uraemic patients and those on dialysis therapy. Carnitine treatment has cardiovascular benefits including modulation of myocardial metabolism, reduction in necrotic cell death and infarct size, decrease in the incidence of arrhythmias and preservation of mechanical function. This review details the profile of substrate metabolism in the uraemic heart and the impact of carnitine supplementation on metabolism and function of the reperfused heart and finally the experimental and clinical evidence for carnitine replacement therapy, in particular its impact on the uraemic heart via modulation of function and energetics.
Department of Renal Medicine, Hull and East Yorkshire Hospitals NHS Trust and Hull York Medical School, East Yorkshire, HU32JZ, UK.
Rebekah
R
Molyneux
A-M
AM
Seymour
Sunil
S
Bhandari
D002331:Carnitine / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000517:prevention & control / Q000628:therapy*; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D006435:Renal Dialysis / Q000379:methods*
D002331:Carnitine