[Frontiers in Bioscience E2, 1492-1501, June 1, 2010]
Functional and metabolic adaptation in uraemic cardiomyopathy
Katie Smith1, David Semple1, Dunja Aksentijevic2, Sunil Bhandari3, Anne-Marie L. Seymour1
1Department of Biological Sciences and Hull York Medical School, University of Hull, Kingston-upon-Hull, United Kingdom, 2Department of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom, 3Department of Renal Medicine, Hull and East Yorkshire Hospital NHS Trust, Kingston-upon-Hull, United Kingdom
TABLE OF CONTENTS
Cardiovascular complications are the leading cause of death in patients with chronic kidney disease (CKD). The uraemic heart undergoes substantial remodelling, including left ventricular hypertrophy (LVH), an important determinant of heart failure. LVH results in a shift in myocardial substrate oxidation from fatty acids towards carbohydrates however, whether this metabolic adaptation occurs in the uraemic heart is unknown. The aim of this study was to investigate the progression of kidney dysfunction in parallel with cardiac remodelling in experimental uraemia. Experimental uraemia was induced surgically via a subtotal nephrectomy. At 3, 6 and 12 weeks post-surgery, renal function, LVH, in vitro cardiac function and metabolic remodelling using 13C-NMR were assessed. Uraemic animals exhibited anaemia and kidney dysfunction at 3 weeks, with further deterioration as uraemia progressed. By 12 weeks, uraemic hearts showed marked LVH, preserved cardiac function and markedly reduced fatty acid oxidation. This change in substrate preference may contribute to the deterioration of cardiac function in the uraemic heart and ultimately failure.