- A model for cooperative gating of L-type Ca2+ channels and its effects on cardiac alternans dynamics. [Journal Article]
- PCPLoS Comput Biol 2018; 14(1):e1005906
- In ventricular myocytes, membrane depolarization during the action potential (AP) causes synchronous activation of multiple L-type CaV1.2 channels (LTCCs), which trigger the release of calcium (Ca2+)...
In ventricular myocytes, membrane depolarization during the action potential (AP) causes synchronous activation of multiple L-type CaV1.2 channels (LTCCs), which trigger the release of calcium (Ca2+) from the sarcoplasmic reticulum (SR). This results in an increase in intracellular Ca2+ (Cai) that initiates contraction. During pulsus alternans, cardiac contraction is unstable, going from weak to strong in successive beats despite a constant heart rate. These cardiac alternans can be caused by the instability of membrane potential (Vm) due to steep AP duration (APD) restitution (Vm-driven alternans), instability of Cai cycling (Ca2+-driven alternans), or both, and may be modulated by functional coupling between clustered CaV1.2 (e.g. cooperative gating). Here, mathematical analysis and computational models were used to determine how changes in the strength of cooperative gating between LTCCs may impact membrane voltage and intracellular Ca2+ dynamics in the heart. We found that increasing the degree of coupling between LTCCs increases the amplitude of Ca2+ currents (ICaL) and prolongs AP duration (APD). Increased AP duration is known to promote cardiac alternans, a potentially arrhythmogenic substrate. In addition, our analysis shows that increasing the strength of cooperative activation of LTCCs makes the coupling of Ca2+ on the membrane voltage (Cai→Vm coupling) more positive and destabilizes the Vm-Cai dynamics for Vm-driven alternans and Cai-driven alternans, but not for quasiperiodic oscillation. These results suggest that cooperative gating of LTCCs may have a major impact on cardiac excitation-contraction coupling, not only by prolonging APD, but also by altering Cai→Vm coupling and potentially promoting cardiac arrhythmias.
- Pulsus alternans in a child with dilated cardiomyopathy. [Journal Article]
- CYCardiol Young 2018; 28(3):479-481
- A previously healthy 21-month-old presented with new-onset dilated cardiomyopathy. Evaluation noted pulsus alternans, with beat-to-beat alternations in aortic pulse wave amplitude, both clinically an...
A previously healthy 21-month-old presented with new-onset dilated cardiomyopathy. Evaluation noted pulsus alternans, with beat-to-beat alternations in aortic pulse wave amplitude, both clinically and on diagnostic studies. Pulsus alternans is an infrequent, complex pathophysiologic sign often associated with severe heart failure. The mechanisms are incompletely understood, but theorised aetiologies include beat-to-beat changes in left ventricular loading conditions, variations in myocardial oxygen supply/demand, and alternations in myocardial contractility. Recognition of pulsus alternans is important as it provides significant clinical information, may suggest suboptimal medical management, and may be the first warning sign of severe cardiac dysfunction.
- Electrical and mechanical alternans during ventricular tachycardia with moderate chronic heart failure. [Journal Article]
- JEJ Electrocardiol 2018 Jan - Feb; 51(1):33-37
- A chronic heart failure (CHF) rat underwent epicardial programmed electrical stimulation (PES). Ventricular tachycardia (VT) developed during PES. Mechanical alternans was noted despite fixed tachyca...
A chronic heart failure (CHF) rat underwent epicardial programmed electrical stimulation (PES). Ventricular tachycardia (VT) developed during PES. Mechanical alternans was noted despite fixed tachycardia cycle length. Anti-tachycardia pacing attempts initiated a second VT that generated pulse intermittently and then degenerated into pulseless VT with electrical alternans.To our knowledge electrical and mechanical alternans have not been recorded in animal models of CHF during VT. The distinct events of mechanical alternans and electrical alternans may be indicative of progressively worsened calcium handling in the compromised cardiomyocytes.Although ion channel differences between rodents and humans exist, this work attempts to demonstrate this rat model's usefulness in understanding cardiac electrophysiology in CHF.
- Minimal model for calcium alternans due to SR release refractoriness. [Journal Article]
- CChaos 2017; 27(9):093928
- In the heart, rapid pacing rates may induce alternations in the strength of cardiac contraction, termed pulsus alternans. Often, this is due to an instability in the dynamics of the intracellular cal...
In the heart, rapid pacing rates may induce alternations in the strength of cardiac contraction, termed pulsus alternans. Often, this is due to an instability in the dynamics of the intracellular calcium concentration, whose transients become larger and smaller at consecutive beats. This alternation has been linked experimentally and theoretically to two different mechanisms: an instability due to (1) a strong dependence of calcium release on sarcoplasmic reticulum (SR) load, together with a slow calcium reuptake into the SR or (2) to SR release refractoriness, due to a slow recovery of the ryanodine receptors (RyR2) from inactivation. The relationship between calcium alternans and refractoriness of the RyR2 has been more elusive than the corresponding SR Ca load mechanism. To study the former, we reduce a general calcium model, which mimics the deterministic evolution of a calcium release unit, to its most basic elements. We show that calcium alternans can be understood using a simple nonlinear equation for calcium concentration at the dyadic space, coupled to a relaxation equation for the number of recovered RyR2s. Depending on the number of RyR2s that are recovered at the beginning of a stimulation, the increase in calcium concentration may pass, or not, over an excitability threshold that limits the occurrence of a large calcium transient. When the recovery of the RyR2 is slow, this produces naturally a period doubling bifurcation, resulting in calcium alternans. We then study the effects of inactivation, calcium diffusion, and release conductance for the onset of alternans. We find that the development of alternans requires a well-defined value of diffusion while it is less sensitive to the values of inactivation or release conductance.
- Pulsus alternans: a visual clue to a grave disorder! [Journal Article]
- BCBMJ Case Rep 2017 Sep 12; 2017
- Concomitant pulsus and pseudoelectrical alternans in severe systolic dysfunction. [Journal Article]
- HCHeartRhythm Case Rep 2016; 2(3):277-279
- Cibenzoline Abolished Pulsus Alternans in a HOCM Patient. [Journal Article]
- IMIntern Med 2015; 54(17):2273
- Pulsus alternans: Real and pseudo. [Journal Article]
- SJSaudi J Anaesth 2014; 8(2):306
- Pulsus alternans: Doppler demonstration. [Case Reports]
- CircCirculation 2014 Apr 08; 129(14):1540-1
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- Heart failure and pulsus alternans: an unusual presentation of first-degree heart block. [Case Reports]
- CHCirc Heart Fail 2014; 7(1):227-8