Modelling the Effects of Nifedipine on Ventricular and Myometrial Cells of Pregnant Rats

In this study we have used computational models to investigate the effects of nifedipine on two different cell types; the rat ventricular cell and the rat myometrial cell. Nifedipine is a calcium-channel blocker commonly used by health services around the world to treat both cardiovascular conditions (such as high blood pressure) and as a tocolytic to treat pre-term birth. The latter usage is prohibited in pregnant patients with pre-existing heart conditions. By applying discrete blocks to the L-Type calcium channels in each cell model we were able to simulate the presence of nifedipine at varying concentrations. Using the electrical and ionic responses to blocking these channels as indicators, we have been able to quantify and describe the effects of nifedipine in each cell type and compare them qualitatively. Although any level of block will reduce the maximum level of intracellular calcium in the myometrial cell, a 60% block or higher is required to produce a change in the morphology of the calcium transient. It remains to be shown if the dose required to achieve this could result in a patient with a pre-existing heart condition experiencing hypotension or other pathological cardiac conditions during labor, if nifedipine is used as a tocolytic

Cardiac re-entry dynamics & self-termination in DT-MRI based model of Human Foetal Heart

The effect of heart geometry and anisotropy on cardiac re-entry dynamics and self-termination is studied here in anatomically realistic computer simulations of human foetal heart. 20 weeks of gestational age human foetal heart isotropic and anisotropic anatomy models from diffusion tensor MRI data sets are used in the computer simulations. The fibre orientation angles of the heart were obtained from the DT-MRI primary eigenvalues. In a spatially homogeneous electrophysiological mono domain model with the DT-MRI based heart geometries, we initiate simplified Fitz-Hugh-Nagumo kinetics cardiac re-entry at a prescribed location in a 2D slice, and in the full 3D anatomy model. In a slice of the heart, the MRI based fibre anisotropy changes the re-entry dynamics from pinned to anatomical re-entry. In the full 3D MRI based model, the foetal heart fibre anisotropy changes the re-entry dynamics from a persistent re-entry to the re-entry self-termination

A Risk-Benefit Analysis of Maintaining an Aerobic-Endurance Triathlon Training Program During Pregnancy: A Review

Objectives Possible risks and benefits of an endurance-based triathlon training program during pregnancy were assessed. News Vigorous exercise throughout the third trimester can lower birth weight by 400 g, but other indices of fetal well-being are unaffected. Fetal heart rate increases during exercise, remaining within the normal range (120–160 beats min−1). Swimming, cycling and running do not affect fetal morbidity or mortality. Performance indices such as aerobic capacity can be maintained through continuation of training. Prospects and projects Will aid the counselling of women during pregnancy. To date, no research exists regarding triathlon training during pregnancy, future studies could investigate multi-sport training whilst pregnant. Conclusion Pregnancy does not require complete cessation of triathlon training and can include each of the three sports. However, maternal heart rate (MHR) should not exceed 90% of maximal

Phase entrainment of induced ventricular fibrillation: A human feasibility and proof of concept study

Cardioversion and defibrillation by a single high energy shock applied by myocardial or body surface electrodes is painful, causes long term tissue damage, and is associated with worsening long term outcomes, but is almost always required for treatment of ventricular fibrillation . As a initial step towards developing methods that can terminate ventricular arrhythmias painlessly, we aim to determine if pacing stimuli at a rate of 5/s applied via an implantable cardiac defibrillator (ICD) can modify human ventricular fibrillation. In 8 patients undergoing defibrillation testing of a new/exchanged intracardiac defibrillator, five seconds of pacing at five stimuli per second was applied during the 10-20 seconds of induced ventricular fibrillation before the defibrillation shock was automatically applied, and the cardiac electrograms recorded and analyzed. The high frequency pacing did not entrain the ventricular fibrillation, but altered the dominant frequency in all 8 patients, and modulated the phase computed via the Hilbert Transform, in four of the patients. In this pilot study we demonstrate that high frequency pacing applied via ICD electrodes during VF can alter the dominant frequency and modulate the probability density of the phase of the electrogram of the ventricular fibrillation

Computational Modelling of Cardiac Electrophysiological Changes in Malarial Fever

Cardiac function is impaired in severe malarial fever, and ECGs show changes associated with repolarization. These could contribute to mortality via ventricular arrhythmia. The cardiac effects could be due to the malarial parasite load in the heart, specific cardio-toxic effects of the parasite or cardio-toxic effects of antimalarial agents. We construct a simple 1-dimensional electrophysiological model for the physico-chemical changes clinically observed during malarial fever: with temperature, pH and [ionic]plasma changes. The model can quantitatively reproduce the tachycardia and QTc prolongation seen in the adult, and shortening seen in the child during malarial fever

Self-terminating re-entrant cardiac arrhythmias: quantitative characterization

Atrial and ventricular tachyarrhythmia are often sustained by re-entrant propagation, and explained by deterministic models. A quantitative, stochastic description of self-termination provides an alternative to the current paradigm for re-entrant tachyarrhythmia - that of triggers and a substrate, modelled by parametrically heterogeneous deterministic partial differential equations. Atrial and ventricular data was from recordings obtained during routine clinical monitoring and treatment, either noninvasively or invasively. Atrial and ventricular tachycardia are characterised by their initiation times and durations, re-presented as instantaneous rates, whose means estimate transition probabilities/s for onset and termination. These estimated probabilities range from 10(-9) to 10(-1)/s

Carbon Monoxide Effects on Electrophysiological Mechanisms of Ventricular Arrhythmogenesis

Increased dissolved carbon monoxide decreases ICa,L IK1 and IKr, and increases late INa currents in rat and guinea pig patch-clamped isolated ventricular myocytes. Action potentials are prolonged. These effects are reproduced by scaling the currents in the Gattoni et al., 2016 (rat) and Luo and Rudy, 1994 (guinea-pig) cell models. Using the same scaling of currents in the O’Hara-Rudy (2011) models the endo-, mid-myo- and epi-cardial APD90 is prolonged. CO abolishes alternans in endo-, and induces alternans in mid-myo -cardial cell models at cycle lengths < 280ms. In the homogenous human ventricular tissue models these CO effects decrease epi-, endocardial conduction velocities from 0.4 to 0.32m/s, and increase the widths of the vulnerable windows by +9%, +8% . In the ventricular wall model (a third each of endo-, mid-myo- and epicardial) CO increased transmural propagation times from 44 to 55 ms and maximal difference in propagating APD from 68 to 73 ms. The computed effects of CO on human ventricular tissue are pro-arrhythmogenic

Imaging, biomarker and invasive assessment of diffuse left ventricular myocardial fibrosis in atrial fibrillation

Background Using cardiovascular magnetic resonance imaging (CMR), it is possible to detect diffuse fibrosis of the left ventricle (LV) in patients with atrial fibrillation (AF), which may be independently associated with recurrence of AF after ablation. By conducting CMR, clinical, electrophysiology and biomarker assessment we planned to investigate LV myocardial fibrosis in patients undergoing AF ablation. Methods LV fibrosis was assessed by T1 mapping in 31 patients undergoing percutaneous ablation for AF. Galectin-3, coronary sinus type I collagen C terminal telopeptide (ICTP), and type III procollagen N terminal peptide were measured with ELISA. Comparison was made between groups above and below the median for LV extracellular volume fraction (ECV), followed by regression analysis. Results On linear regression analysis LV ECV had significant associations with invasive left atrial pressure (Beta 0.49, P = 0.008) and coronary sinus ICTP (Beta 0.75, P < 0.001), which remained significant on multivariable regression. Conclusion LV fibrosis in patients with AF is associated with left atrial pressure and invasively measured levels of ICTP turnover biomarker

An experimental study on the response of blanket bog vegetation and water tables to ditch blocking

We studied the effect of ditch blocking on vegetation composition and water-table depths in a blanket peatland. Measurements were made for a period of four years (water tables) and five years (vegetation) in the inter-ditch areas of three experimental treatments: (i) open ditches, (ii) ditches blocked with closely-spaced dams and (iii) ditches partially infilled with peat and blocked with dams. It is often assumed that ditch blocking will lead to an increase in the abundance of Sphagnum and, potentially, a reduction in the abundance of sedges, particularly the cotton grasses. However, our data show no treatment effects on the abundance of either group. We did find an effect of time, with the abundance of both sedges and Sphagnum spp. varying significantly between some years. For the sedges there was no systematic change over time, while for the Sphagnum spp. abundance tended to increase through the study period. This systematic change was not related to a measure of the vigour of the sedges, although vigour was lower towards the end of the study compared to the beginning. Our vegetation data are consistent with our water-table data. As with plant type abundance, we did not find any statistically significant differences in water-table depths between treatments, both for annual averages and summer averages. We comment on why ditch blocking does not seem to have affected water tables and vegetation composition at our study site

Inhibition of the voltage-gated potassium channel Kv1.5 by hydrogen sulfide attenuates remodeling through S-nitrosylation-mediated signaling

The voltage-gated K⁺ channel plays a key role in atrial excitability, conducting the ultra-rapid rectifier K⁺ current (IKur) and contributing to the repolarization of the atrial action potential. In this study, we examine its regulation by hydrogen sulfide (H₂S) in HL-1 cardiomyocytes and in HEK293 cells expressing human Kv1.5. Pacing induced remodeling resulted in shorting action potential duration, enhanced both Kv1.5 channel and H₂S producing enzymes protein expression in HL-1 cardiomyocytes. H₂S supplementation reduced these remodeling changes and restored action potential duration through inhibition of Kv1.5 channel. H₂S also inhibited recombinant hKv1.5, lead to nitric oxide (NO) mediated S-nitrosylation and activated endothelial nitric oxide synthase (eNOS) by increased phosphorylation of Ser1177, prevention of NO formation precluded these effects. Regulation of Ikur by H₂S has important cardiovascular implications and represents a novel and potential therapeutic target