Page 60 - YORAM RUDY BOOK FINAL

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Figure 2.39. Alternans: APD (A and C) and the calcium transient (CaT, B and D) rate-adaptation
curves. Insets show bifurcation portions on enlarged scale. A and B: guinea pig. C and D: canine.
From Livshitz and Rudy [42]. Inset in (C) shows experimental data (Hua et. al. [150], reproduced
with permission from Wolter Kluwers Health Inc.).

reveals that clamping I Ca,L does not eliminate action-potential or Ca-transient alternans;
however, it reduces the amplitude of APD alternans. Additional simulations identified the
Na -Ca exchange current, I NaCa , as the major coupling link between Ca alternans and APD
2+
+
alternans. From a clinical perspective, it should be noted that heart failure shifts the onset of APD
alternans to slower heart rates and augments its amplitude . Heart failure is also associated with
151
up-regulation of I NaCa . These observations support the role of I NaCa as the major Ca-APD coupler
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during alternans.