ArticlePloS one2017
Sensitivity analysis revealing the effect of modulating ionic mechanisms on calcium dynamics in simulated human heart failure.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 36 citations in OpenAlex.
- Can in silico models predict drug-induced cardiac risk in vulnerable populations?Toxicology reports · 2026Article
- Intracellular Ionic Remodeling During Fetal Development of Hereditary Cardiomyopathy of the Hamster.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Article
- Reduced gap junction coupling amplifies the effects of cardiomyocyte variability and destabilizes the heartbeat.Physiological reports · 2025Article
- An Electromechanical Model-Based Study on the Dosage Effects of Ranolazine in Treating Failing HCM Cardiomyocyte.Cellular and molecular bioengineering · 2025Article
- Article
- The recent advance and prospect of natural source compounds for the treatment of heart failure.Heliyon · 2024Review
- Macrophage-Dependent Interleukin-6-Production and Inhibition ofInternational journal of molecular sciences · 2021Article
- Quantitative analysis of variability in an integrated model of human ventricular electrophysiology and β-adrenergic signaling.Journal of molecular and cellular cardiology · 2020Article
- Identifying Drug Response by Combining Measurements of the Membrane Potential, the Cytosolic Calcium Concentration, and the Extracellular Potential in Microphysiological Systems.Frontiers in pharmacology · 2020Article
- The Protective Effect of Qishen Granule on Heart Failure after Myocardial Infarction through Regulation of Calcium Homeostasis.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblasts.PloS one · 2019Article
- Optimization of Lead Placement in the Right Ventricle During Cardiac Resynchronization Therapy. A Simulation Study.Frontiers in physiology · 2019Article
- CaFrontiers in physiology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abnormal intracellular Ca2+ handling is the major contributor to the depressed cardiac contractility observed in heart failure. The electrophysiological remodeling associated with this pathology alters both the action potential and the Ca2+ dynamics, leading to a defective excitation-contraction coupling that ends in mechanical dysfunction. The importance of maintaining a correct intracellular Ca2+ concentration requires a better understanding of its regulation by ionic mechanisms. To study the electrical activity and ionic homeostasis of failing myocytes, a modified version of the O'Hara et al. human action potential model was used, including electrophysiological remodeling. The impact of the main ionic transport mechanisms was analyzed using single-parameter sensitivity analyses, the first of which explored the modulation of electrophysiological characteristics related to Ca2+ exerted by the remodeled parameters. The second sensitivity analysis compared the potential consequences of modulating individual channel conductivities, as one of the main effects of potential drugs, on Ca2+ dynamic properties under both normal conditions and in heart failure. The first analysis revealed the important contribution of the sarcoplasmic reticulum Ca2+-ATPase (SERCA) dysfunction to the altered Ca2+ homeostasis, with the Na+/Ca2+ exchanger (NCX) and other Ca2+ cycling proteins also playing a significant role. Our results highlight the importance of improving the SR uptake function to increase Ca2+ content and restore Ca2+ homeostasis and contractility. The second sensitivity analysis highlights the different response of the failing myocyte versus the healthy myocyte to potential pharmacological actions on single channels. The result of modifying the conductances of the remodeled proteins such as SERCA and NCX in heart failure has less impact on Ca2+ modulation. These differences should be taken into account when designing drug therapies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.