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Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
Published on: September 18, 2017
Calcium and potassium changes during haemodialysis alter ventricular repolarization duration: in vivo and in silico
Stefano Severi1, Eleonora Grandi, Chiara Pes
1Biomedical Engineering Laboratory, D.E.I.S., University of Bologna, Via Venezia 52, I-47023 Cesena, Italy. stefano.severi@unibo.it
Insights
Low calcium and potassium levels during hemodialysis (HD) can prolong the QT interval (QTc), increasing arrhythmia risk. Careful dialysate management is crucial to prevent dangerous cardiac repolarization changes in HD patients.
Area of Science:
- Cardiology
- Nephrology
- Computational Biology
Background:
- Ventricular repolarization duration, measured by QT interval, is altered in hemodialysis (HD) patients.
- The exact mechanisms and direction of these QT interval changes remain unclear.
Purpose of the Study:
- To investigate the impact of varying dialysate calcium (Ca2+) and potassium (K+) levels on QT interval duration (QTc) in HD patients.
- To assess cellular-level electrophysiological changes using a cardiomyocyte action potential model to explain observed QTc alterations.
Main Methods:
- Tested different dialysate Ca2+ and K+ concentrations to observe their effect on end-HD plasma levels and QTc.
- Employed a human cardiomyocyte action potential (AP) model for in silico analysis of Ca2+ and K+ effects on QTc.
Main Results:
- QTc was significantly prolonged in HD patients with lower Ca2+ (1.25 mM vs 2 mM) and lower K+ (2 mM vs 3 mM) dialysate concentrations.
- In silico analysis confirmed that reduced K+ and Ca2+ prolonged ventricular AP duration, correlating with QTc variations.
- Simulations predicted critically prolonged AP and QT intervals when both low K+ and Ca2+ were present concurrently, indicating a potential arrhythmogenic factor.
Conclusions:
- Computational modeling of ventricular AP duration is valuable for predicting QTc changes due to simultaneous K+ and Ca2+ variations.
- Dialysate Ca2+ levels should be managed to avoid critical reductions in serum Ca2+, particularly in patients at risk of end-dialysis hypokalemia.
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.
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