Stefano Severi

C3MIG 7 maggio 2009

Introduzione

• It is well known that changes in serum calcium influence the cardiac electrical activity particularly affecting ventricular repolarization

• The primary electrocardiographic manifestation of hypocalcaemia is QTc prolongation, which is associated with increased risk of early after-depolarizations and triggered arrhythmias

• hypercalcaemia exerts an opposite effect on the ECG with the hallmark of abnormal shortening of the QTc interval

Introduzione

• Ca2+-dependency of repolarization is particularly relevant in dialysis, when plasma Ca2+ levels may vary widely

• During dialysis, QTc was found to inversely correlate with plasma Ca2+

4

RELATION BETWEEN CALCIUM CONCENTRATION AND ACTION POTENTIAL (AP)

Calcium currents influence the plateau duration: in particular the QT interval increases when decreasing [Ca2+] is observed.

Copyright ©2005 American Heart Association

Bai, C.-X. et al. Circ Res 2005;96:64-72

Effects of rise in [Ca2+]o on APDBackground

The aim of the present study was to identify the ionic mechanism/s likely to underlie the APD dependency on [Ca2+]o by using an in silico approach. To this purpose, new formulations of the Ca2+-dependency of IKs, IKr and ICaL were incorporated in the TNNP model of the human ventricular AP

Aim

Methods

• Ten Tusscher human ventricular model (Am J Physiol Heart Circ Physiol 2004)

• [Ca2+]o ranging from 1 to 3 mM was analysed

Metodi

Metodi

fCa inf fca fca fca N fCa

D fCa

fca 1

1 [Ca2]ia fCa

8

fca 0.1

1 e([Ca 2 ]i b fCa )

0.0001

fca g fCa

1 e([Ca 2 ]i 0.00075)

0.0008

Metodi

Metodi

Metodi

Figure 10. Influence of [Ca2+]i homeostasis on L-type Ca2+ current, charge transfer and L-type channel inactivation (fAP) during an action potential with

an overshoot of 50 mV The panels show from top to bottom: command voltage, matching averaged 100 µM Cd2+-sensitive currents, averaged charge transfers, and averaged fAP values

plotted as function of time. A, effect of buffering [Ca2+]i with 10 mM EGTA (   , n = 9) or 10 mM BAPTA (   , n = 14). Recordings were obtained from different

cells. B, effect of inhibition of the SR by 1 µM ryanodine and 1 µM thapsigargin (   , n = 19), and of blocking Na+-Ca2+ exchange by rapidly substituting Li+ for Na+ in the external solution (   , n = 8). Recordings were made on different cells. The data recorded under control conditions (   , n = 24) are redrawn from Figs 3 and 5 to allow comparison of the results. Significance of difference from control values was tested using Student's t test (* P < 0·05; ** P < 0·01).

LINZ & MEYER TEN TUSSCHER GRANDI & SEVERI

3.65 3.7 3.75 3.8 3.85 3.90

0.5

1

3.7 3.75 3.8 3.85 3.9 3.950

0.5

1

1.5

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we have shown (Fig. 6) that the AP prolongs as the store is depleted and shortens as the SR is refilled with Ca2+ in about 20 beats. A similar time course has been shown experimentally [47]: after removal of caffeine (which empties the SR, suppresses the Ca2+ transient and prolongs the AP), the APD is gradually shortened to basal length in parallel with the restoration of the magnitude of the Ca2+ transient during the refilling of the SR [49] as the rat cardiomyocytes are stimulated.

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Ringraziamenti