Calcium and potassium changes during haemodialysis alter ventricular repolarization duration: in vivo and in silico analysis

Background. Alterations of ventricular repolarization duration, as measured by the QT interval, are frequently observed in haemodialysis (HD) patients. The nature and the sign of these changes are not yet fully understood. Methods. Different dialysate K + and Ca 2+ levels, leading to different end-HD plasma concentrations in the patient, have been tested in the present study in terms of their impact on QTc. A model of the human cardiomyocyte action potential (AP) has been used to assess in silico whether the changes in Ca 2+ and K + were able to justify at the cellular level the observed alterations of QTc. Results. QTc was prolonged in HDs with low (1.25 mM) versus high (2 mM) Ca 2+ (424 ± 33 versus 400 ± 28 ms, P < 0.05) and in HDs with low (2 mM) versus high (3 mM) K + (420 ± 35 versus 399 ± 36 ms, P < 0.05). These alterations were confirmed at the cellular level by computational analysis showing prolongation of ventricular AP at low K + and low Ca 2+ at the same extent of the measured QTc variations. Numerical simulation predicted a critically long AP (and QT) when considering low K + and Ca 2+ simultaneously, suggesting the concurrent lowering of Ca 2+ and K + as a potential arrhythmogenic factor. Conclusions. Numerical simulations of the ventricular AP may be useful to quantitatively predict the complex dependence of AP duration on simultaneous changes in Ca 2+ and K + . Moreover, Ca 2+ content in the dialysate should be designed not to critically lower serum Ca 2+ , especially in sessions at risk of end-dialysis hypokalaemia.