Prolonged calcium transients and myocardial remodelling in early experimental uraemia.
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 Ca(2+) handling (using Fura-2) was investigated. Up to 20 consecutive transients were averaged as the extracellular Ca(2+) 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 Ca(2+)) no significant differences in intracellular Ca(2+) were observed, but in high extracellular Ca(2+) the uraemic cells were slower to return to diastolic intracellular Ca(2+) 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.
McMahon
Aisling C
AC
Anthony Raine Research Laboratories, Barts and The London Queen Mary's School of Medicine and Dentistry, University of London, London, UK. amcmahon@stvincents.com.au
Greenwald
Stephen E
SE
Dodd
Susan M
SM
Hurst
Martin J
MJ
Raine
Anthony E G
AE
D000818:Animals; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism*; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate; D007425:Intracellular Membranes / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009392:Nephrectomy / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014508:Urea / Q000097:blood; D014511:Uremia / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020257:Ventricular Remodeling
D014508:Urea; D003404:Creatinine; D002118:Calcium