Mechanisms underlying cardiac alternans in a human ventricular myocyte mathematical model

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Mechanisms underlying cardiac alternans in a human ventricular myocyte mathematical model
Mattiazzi, Alicia; Alejandra Cely-Ortiz; Juan Ignacion Felice; Elena Catalina Lascano; Carlos Alfredo Valverde; Luis Alberto Gonano; María Matilde Said; Cecilia Mundiña-Weilenmann, 2026, "Mechanisms underlying cardiac alternans in a human ventricular myocyte mathematical model", https://datos.unlp.edu.ar/citation?persistentId=perma:10915dataset9XAGC5, Universidad Nacional de La Plata, V1, UNF:6:4Pjk1b/xfyT9Wa7JvC2RSw== [fileUNF]
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Description
Cardiac alternans is a beat-to-beat oscillation in action potential duration and intracellular Ca²⁺ transients that develops at rapid heart rates and is associated with electrical instability and an increased risk of ventricular arrhythmias. The study uses a validated mathematical model of the human ventricular myocyte to dissect the relative contribution of voltage-dependent mechanisms and intracellular Ca²⁺ handling to the initiation and maintenance of alternans. In particular, the simulations examine the roles of sarcoplasmic reticulum Ca²⁺load and release, RyR2 refractoriness, and SERCA-mediated Ca²⁺ reuptake during an abrupt increase in pacing frequency. The supplementary figures and tables provide additional analyses supporting the main results and may be reused for comparison with other computational or experimental studies of cardiac excitation–contraction coupling, Ca²⁺ handling, and arrhythmogenesis.
Subject Medicine, Health and Life Sciences
Keyword Cardiac alternans, Calcium handling, Mathematical model
Related Publication Cely Ortizi, A., et al. (2026). Insights into the mechanisms underlying cardiac alternans using a human ventricular myocyte mathematical model. American Journal of Physiology-Cell Physiology. Manuscript C-90099.2026. Submitted for publication.
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CC BY-NC-SA 4.0

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LEAME.md
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Published Aug 28, 2026
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MD5: 4dc84b226051d323a5142cd9eda8197f
Documento explicativo sobre lo que contiene este conjunto de datos.
Documentación
README.md
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Published Aug 28, 2026
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MD5: 115a67b7b73d79c671654fdde7f50f9d
Explanatory document on what this dataset contains.
Documentación
figure_1_RyR2_model.png
figure_1_RyR2_model.png
figures/PNG Image - 89.8 KB
Published Aug 28, 2026
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MD5: c16252f14684aa4b0b3be8892cf08727
Four-state Markov model of the RyR2. Modified from Shannon et al. (8). The channel can be found in 4 states: resting or closed (R), open (O), inactivated (I) and resting inactivated (RI). R, I, and RI are non-conducting states while O is the conducting state.
Datos
Preview "figures/figure_1_RyR2_model.png"
figure_2_150bpm_no_alt.png
figure_2_150bpm_no_alt.png
figures/PNG Image - 224.7 KB
Published Aug 28, 2026
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MD5: 9ac51fea99ce7cbfe3af143fac3c9b6d
Increasing stimulation rate to 150 bpm does not evoke alternans. Increasing stimulation frequency up to 150 beats/min failed to produce Ca²⁺ alternans at 1.2 mM [Ca²⁺]ₒ. Only a few irregular beats are observed immediately after the frequency change.
Datos
Preview "figures/figure_2_150bpm_no_alt.png"
figure_3_rabbit_alt_phases.png
figure_3_rabbit_alt_phases.png
figures/PNG Image - 118.8 KB
Published Aug 28, 2026
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MD5: b97d39db1f9d38dafa3571fb966d2e95
Experimental results obtained by Picht et al. (10) in a rabbit myocyte stimulated at 2.0 Hz after complete depletion of SR with caffeine. The authors described a first phase without alternans (equivalent to our second phase), a third phase with alternans in which myocytes relaxed completely (at least the first beat of phase b), analogue to our phase 3, and a third phase in which myocytes failed to completely relax (similar to our phase 4).
Datos
Preview "figures/figure_3_rabbit_alt_phases.png"
figure_4_APD_ICaL_recovery.png
figure_4_APD_ICaL_recovery.png
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MD5: 8689e3e02959f350ae1cc884dc22a476
APD restitution and incomplete ICaL recovery support a predominantly voltage-driven mechanism during P1. (A) APD restitution curve as a function of the preceding diastolic interval (DI). Red symbols indicate the beats corresponding to the early alternating phase after the abrupt increase in pacing rate. These beats fall within a steep region of the restitution relationship. (B) Recovery of peak inward ICaL as a function of DI. Red symbols indicate the DI range sampled during P1, corresponding to the red points in panel A. In this range, peak ICaL remains below its fully recovered value, indicating incomplete recovery of ICaL during P1.
Datos
Preview "figures/figure_4_APD_ICaL_recovery.png"
figure_5a_RyR2_block_voltage_alt.png
figure_5a_RyR2_block_voltage_alt.png
figures/PNG Image - 26.6 KB
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MD5: b1bdbad2be4eab1f8134bb2f100df5be
Simulation of alternans at [Ca²⁺]ₒ = 2.0 mM in a human ventricular myocyte mathematical model in the presence of complete RyR2 blockade. The absence of CaT did not prevent voltage driven alternans, indicating that even at commonly used experimental [Ca²⁺]ₒ, Ca²⁺ cycling alternans are not necessary for the development of voltage alternans.
Datos
Preview "figures/figure_5a_RyR2_block_voltage_alt.png"
figure_5b_BAPTA_AP_alt.png
figure_5b_BAPTA_AP_alt.png
figures/PNG Image - 711.5 KB
Published Aug 28, 2026
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MD5: 9af3032becfaecc5c396e42b93e99a10
Experimental data from Warren and Poelzing (11), obtained in isolated rabbit ventricle myocytes, showing AP alternans induced by rapid pacing in the presence of BAPTA to abolish Ca²⁺ transients.
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Preview "figures/figure_5b_BAPTA_AP_alt.png"
figure_6_CaMKII_FDAR.png
figure_6_CaMKII_FDAR.png
figures/PNG Image - 93.7 KB
Published Aug 28, 2026
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MD5: ec3a9070d07364ebd2aea440664c08de
The increase in stimulation frequency in the present simulations is associated with the described CaMKII-mediated increase in the velocity of relaxation (FDAR) (12,13). Red (70 bpm) and green (182 bpm) traces represent the exponential fit of the relaxation part of the calcium transient. Tau constant of this fit was used to compare velocity of relaxation.
Datos
Preview "figures/figure_6_CaMKII_FDAR.png"
figure_7_SR_uptake_increase.png
figure_7_SR_uptake_increase.png
figures/PNG Image - 613.7 KB
Published Aug 28, 2026
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MD5: d5b6f3f4581911701ee09d0cc41d9b2c
Increase in SR Ca²⁺ uptake velocity. SR Ca²⁺ uptake was increased by 50% at the beginning of P4 (arrow).
Datos
Preview "figures/figure_7_SR_uptake_increase.png"
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