March 27, 2014PLoS Computational BiologyOpen Access

Comprehensive Analyses of Ventricular Myocyte Models Identify Targets Exhibiting Favorable Rate Dependence

Q: What is the clinical evidence from this study?

Population: Cardiac arrhythmias (in silico ventricular myocyte models). Intervention: Simulated ionic current perturbations vs. Baseline model parameters. Primary outcome: Rate-dependent effects on action potential duration (APD) at slow (0.2 Hz) and fast (2 Hz) rates.

View Full Paper

Ask AI

Bookmark

Key result

Simulated perturbations of inward rectifier potassium current and the sodium-potassium pump in 13 ventricular myocyte models produced favorable forward rate-dependent action potential prolongation.

Population

13 ventricular myocyte models

Comparison

Simulated perturbations to ionic current… vs Baseline unperturbed models / comparison between…

Design

Preclinical

Authors

MCMegan A. CumminsUniversity of Kentucky HealthCare PDPavan J. DalalMount Sinai Hospital MBMarco BuganaUniversity of Bologna

Discussion

Member takes

Implication

May guide forward rate-dependent antiarrhythmic targets; leaves open translation to human or in vivo arrhythmia suppression.

Structured PICO

Population

In silico study analyzing 13 ventricular myocyte models to predict the rate-dependent effects of changes in multiple model parameters on action potential duration.

Intervention

Simulated perturbations to ionic current properties (average of 40 parameters tested per model) at slow (0.2 Hz) and fast (2 Hz) pacing rates

Comparator

Baseline unperturbed models / comparison between slow and fast pacing rates

Outcome

Action potential duration (APD) rate dependence (forward vs reverse rate dependence)surrogate

Computational modeling of ventricular myocytes identifies inward rectifier potassium current and the sodium-potassium pump as potential targets for forward rate-dependent antiarrhythmic drugs, which could overcome the proarrhythmic risks of current reverse rate-dependent agents.

Limitations

Regression-based sensitivity analysis implicitly assumes linear relationships between parameters and model outputs.
Examined isolated cell models at steady-state pacing, not multicellular models.
Did not consider the effects of beta-adrenergic stimulation.
Modeled perturbations as simple parameter changes rather than rate-dependent drug binding.

Cite This Study

Cummins et al. (2014) studied Cardiac arrhythmias (in silico ventricular myocyte models). Simulated ionic current perturbations vs. Baseline model parameters was evaluated on Rate-dependent effects on action potential duration (APD) at slow (0.2 Hz) and fast (2 Hz) rates. Simulated perturbations of inward rectifier potassium current and the sodium-potassium pump in 13 ventricular myocyte models produced favorable forward rate-dependent action potential prolongation.

synapsesocial.com/papers/6a208886ee274fb2963e8944 https://doi.org/10.1371/journal.pcbi.1003543

View Full Paper

Ask AI

Bookmark

Comprehensive Analyses of Ventricular Myocyte Models Identify Targets Exhibiting Favorable Rate Dependence

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Comprehensive Analyses of Ventricular Myocyte Models Identify Targets Exhibiting Favorable Rate Dependence

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Also Consider

Also Consider