Myocardial function, energy provision, and carnitine deficiency in experimental uremia.
Cardiac complications are the leading cause of mortality in patients with chronic renal failure. Secondary carnitine deficiency, which is frequently observed in hemodialysis patients, has been associated with cardiac hypertrophy and heart failure and may impair myocardial fatty acid oxidation. In chronic kidney disease, impaired carnitine homeostasis also may affect myocardial metabolism. In this study, myocardial function and substrate oxidation in conjunction with carnitine deficiency were investigated in experimental renal failure. Uremia was induced in male Sprague-Dawley rats via a two-stage five-sixths nephrectomy. Cardiac function and substrate oxidation were assessed in vitro by means of isovolumic perfusion using 13C nuclear magnetic resonance at 3 and 6 wk of uremia. Renal impairment as assessed by serum creatinine was more severe initially and was associated with a significant deficiency in serum free carnitine (43%; P < 0.001) and elevated acyl carnitine/free carnitine ratio. Myocardial tissue carnitine concentrations, however, were unaffected. A moderate degree of cardiac hypertrophy (10 to 14%; P < 0.05) was observed in uremia without evidence of dysfunction or changes in myocardial substrate utilization. It is concluded that renal dysfunction is associated with cardiac hypertrophy in the presence of normal myocardial carnitine levels, despite a significant depletion in serum carnitine. This may be a factor in maintaining normal cardiac function and metabolism.
Reddy
Veena
V
Department of Biological Sciences, University of Hull, Hull, HU6 7RX, UK.
Bhandari
Sunil
S
Seymour
Anne-Marie L
AM
D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology; D002331:Carnitine / Q000097:blood / Q000172:deficiency* / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004734:Energy Metabolism; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000378:metabolism / Q000503:physiopathology*
D003404:Creatinine; D002331:Carnitine