Nephrol Dial Transplant (2002) 17: 759-764
© 2002 European Renal Association-European Dialysis and Transplant Association
Prolonged calcium transients and myocardial remodelling in early experimental uraemia
1 Anthony Raine Research Laboratories and 2 Department of Histopathology and Morbid Anatomy, Barts and The London Queen Mary's School of Medicine and Dentistry, University of London, London, UK
Background. Cardiovascular disease is the most common cause of premature death in patients with end-stage renal disease, possibly due to a specific ‘uraemic cardiomyopathy’. This study was designed to investigate the cardiac changes induced by a moderate impairment of renal function in a model of uraemia.
Methods. Male Wistar rats (n=11) were rendered uraemic by 5/6 nephrectomy or sham operated (n=11). After 4 weeks, cardiac dimensions were measured from fixed tissue sections using a digital image analysis technique. In parallel groups of animals, cardiac myocytes were isolated and studied for evidence of functional changes attributable to uraemia. After steady-state field stimulation at 0.5 Hz, intracellular Ca2+ handling (using Fura-2) was investigated. Up to 20 consecutive transients were averaged as the extracellular Ca2+ was increased.
Results. The 5/6 nephrectomy group had a 75% reduction in glomerular filtration rate, and a 2- to 3-fold increase in serum urea and creatinine compared with sham-operated control animals (P<0.0001). However, the blood pressure was found to be similar in each group. Histology of the intact hearts (five pairs) showed a significant increase in tissue cross-sectional area (14%; P<0.04), cross-sectional area of the left ventricle (22%; P<0.04), and a significant increase in left ventricular wall thickness (15%; P<0.03). In the single cardiac cell study, under basal conditions (1–2 mM extra-cellular Ca2+) no significant differences in intracellular Ca2+ were observed, but in high extracellular Ca2+ the uraemic cells were slower to return to diastolic intracellular Ca2+ levels (P<0.05).
Conclusions. The data provide evidence of altered myocardial structure and function in early experimental uraemia. The changes described are consistent with concentric hypertrophy of the left ventricle, which occurs in the absence of hypertension.
Keywords: calcium; cardiomyopathy; hypertrophy; myocyte; rat; uraemia
Correspondence and offprint requests to: Dr A. C. McMahon, Department of Cardiology, St Vincent's Hospital, Victoria Street, Sydney, NSW 2010, Australia. Email: amcmahon{at}stvincents.com.au