Molecular Pathogenesis of Cardiac Arrhythmia

Okamoto, Y.; Ono, Koichi

doi:10.3390/biom12101393

Cited by 3 publications

(4 citation statements)

References 14 publications

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Section: Discussionmentioning

confidence: 99%

“…It has been well-established that prolongation of the QT interval is a key arrhythmogenic mechanism and are associated with adverse cardiac outcomes, speci cally sudden cardiac death [25][26][27]. QT prolongation is an indication of delay in ventricular repolarization, which can lead to ectopic ventricular excitation and malignant ventricular arrhythmias [25,26,46]. QT prolongation is often caused by genetic mutations in cardiac ion channels, predominantly K + and Na + channels, and the resulting prolongation of ventricular action potential [47,48].…”

Section: Discussionmentioning

confidence: 99%

“…Electrical excitation and conduction are fundamental to normal cardiac physiology [24]. Cardiac electrical abnormalities play a key role in cardiac diseases and are a major contributor to human morbidity and mortality [25][26][27].…”

mentioning

confidence: 99%

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Association of same-day urinary phenol levels and cardiac electrical alterations: analysis of the Fernald Community Cohort

Rubinstein,

Pinney,

Xie

et al. 2024

Preprint

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Background Exposure to phenols has been linked in animal models and human populations to cardiac function alterations and cardiovascular diseases, although their effects on cardiac electrical properties in humans remains to be established. This study aimed to identify changes in electrocardiographic (ECG) parameters associated with environmental phenol exposure in adults of a midwestern large cohort known as the Fernald Community Cohort (FCC). Methods During the day of the first comprehensive medical examination, urine samples were obtained, and electrocardiograms were recorded. Cross-sectional linear regression analyses were performed. Results Bisphenol A (BPA) and bisphenol F (BPF) were both associated with a longer PR interval, an indication of delayed atrial-to-ventricle conduction, in females (p < 0.05) but not males. BPA combined with BPF was associated with an increase QRS duration, an indication of delayed ventricular activation, in females (P < 0.05) but not males. Higher triclocarban (TCC) level was associated with longer QTc interval, an indication of delayed ventricular repolarization, in males (P < 0.01) but not females. Body mass index (BMI) was associated with a significant increase in PR and QTc intervals and ventricular rate in females and in ventricular rate in males. In females, the combined effect of being in the top tertile for both BPA urinary concentration and BMI was an estimate of a 10% increase in PR interval. No associations were found with the other phenols. Conclusion Higher exposure to some phenols was associated with alterations of cardiac electrical properties in a sex specific manner in the Fernald cohort. Our population-based findings correlate directly with clinically relevant parameters that are associated with known pathophysiologic cardiac conditions in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Association of same-day urinary phenol levels and cardiac electrical alterations: analysis of the Fernald Community Cohort

Rubinstein,

Pinney,

Xie

et al. 2024

Preprint

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“…These states are essential for gaining insights into the characteristics of atomic and molecular systems. For instance, the transition between folded and unfolded states, representing metastable states in proteins, significantly alters the functional attributes of protein molecules. − Additionally, identifying the boundaries of metastable states in superheated crystals and supercooled liquids plays a crucial role in understanding nucleation behavior. , All-atom molecular simulations, however, often face a significant challenge: they tend to get trapped in deep potential wells of lower energy states. , This entrapment necessitates excessively long simulation trajectories to climb the surrounding energy barriers and continue exploring the energy landscape. Such prolonged simulations demand substantial computational resources, rendering them less feasible for many applications.…”

Section: Introductionmentioning

confidence: 99%

GradNav: Accelerated Exploration of Potential Energy Surfaces with Gradient-Based Navigation

Ock,

Mollaei,

Barati Farimani

2024

J. Chem. Theory Comput.

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Exploring the potential energy surface (PES) of molecular systems is important for comprehending their complex behaviors, particularly through the identification of various metastable states. However, the transition between these states is often hindered by substantial energy barriers, demanding prolonged molecular simulations that consume considerable computational resources. Our study introduces the gradient-based navigation (GradNav) algorithm, which accelerates the exploration of the energy surface and enables proper reconstruction of the PES. This algorithm employs a strategy of initiating short simulation runs from updated starting points derived from prior observations to effectively navigate across potential barriers and explore new regions. To evaluate GradNav’s performance, we introduce two metrics: the deepest well escape frame (DWEF) and the search success initialization ratio (SSIR). Through applications on Langevin dynamics within Müller-type PESs and molecular dynamics simulations of the Fs-peptide protein, these metrics demonstrate GradNav’s enhanced ability to escape deep energy wells and its reduced reliance on initial conditions, as denoted by the reduced DWEF values and increased SSIR values, respectively. Consequently, this improved exploration capability enables more precise energy estimations from simulation trajectories.

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Association of same-day urinary phenol levels and cardiac electrical alterations: analysis of the Fernald Community Cohort

Rubinstein,

Pinney,

Xie

et al. 2024

Environ Health

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Background Exposure to phenols has been linked in animal models and human populations to cardiac function alterations and cardiovascular diseases, although their effects on cardiac electrical properties in humans remains to be established. This study aimed to identify changes in electrocardiographic (ECG) parameters associated with environmental phenol exposure in adults of a midwestern large cohort known as the Fernald Community Cohort (FCC). Methods During the day of the first comprehensive medical examination, urine samples were obtained, and electrocardiograms were recorded. Cross-sectional linear regression analyses were performed. Results Bisphenol A (BPA) and bisphenol F (BPF) were both associated with a longer PR interval, an indication of delayed atrial-to-ventricle conduction, in females ( p < 0.05) but not males. BPA combined with BPF was associated with an increase QRS duration, an indication of delayed ventricular activation, in females ( P < 0.05) but not males. Higher triclocarban (TCC) level was associated with longer QTc interval, an indication of delayed ventricular repolarization, in males ( P < 0.01) but not females. Body mass index (BMI) was associated with a significant increase in PR and QTc intervals and ventricular rate in females and in ventricular rate in males. In females, the combined effect of being in the top tertile for both BPA urinary concentration and BMI was an estimate of a 10% increase in PR interval. No associations were found with the other phenols. Conclusion Higher exposure to some phenols was associated with alterations of cardiac electrical properties in a sex specific manner in the Fernald cohort. Our population-based findings correlate directly with clinically relevant parameters that are associated with known pathophysiologic cardiac conditions in humans. Supplementary Information The online version contains supplementary material available at 10.1186/s12940-024-01114-x.

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Molecular Pathogenesis of Cardiac Arrhythmia

Abstract: The heart is a necessary organ for sustaining life in mammals, and it is the first organ to function during early development [...]

Cited by 3 publications

References 14 publications

Association of same-day urinary phenol levels and cardiac electrical alterations: analysis of the Fernald Community Cohort

Association of same-day urinary phenol levels and cardiac electrical alterations: analysis of the Fernald Community Cohort

GradNav: Accelerated Exploration of Potential Energy Surfaces with Gradient-Based Navigation

Association of same-day urinary phenol levels and cardiac electrical alterations: analysis of the Fernald Community Cohort

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