Biology subjects

Iravanian, S.

Publications and source records attributed to Iravanian, S..

4 recordsLinked to original sources

bioRxiv2023

Beyond Alternans: Detection of Higher-Order Periodicity in Ex-Vivo Human Ventricles Before Induction of Ventricular Fibrillation

BackgroundRepolarization alternans, defined as period-2 oscillation in the repolarization phase of the action potentials, is one of the cornerstones of cardiac electrophysiology as it provides a mechanistic link between cellular dynamics and ventricular fibrillation (VF). Theoretically, higher-order periodicities (e.g., period-4, period-8,...) are expected but have very limited experimental evidence. MethodsWe studied explanted human hearts, obtained from the recipients of heart transplantation at the time of surgery, using optical mapping technique with transmembrane voltage-sensitive fluorescent dyes. The hearts were stimulated at an increasing rate until VF was induced. The signals recorded from the right ventricle endocardial surface just before the induction of VF and in the presence of 1:1 conduction were processed using the Principal Component Analysis and a combinatorial algorithm to detect and quantify higher-order dynamics. ResultsA prominent and statistically significant 1:4 peak (corresponding to period-4 dynamics) was seen in three of the six studied hearts. Local analysis revealed the spatiotemporal distribution of higher-order periods. Period-4 was localized to temporally stable islands. Higher-order oscillations (period-5, 6, and 8) were transient and primarily occurred in arcs parallel to the activation isochrones. DiscussionWe present evidence of higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex-vivo human hearts before VF induction. This result is consistent with the period-doubling route to chaos as a possible mechanism of VF initiation, which complements the concordant to discordant alternans mechanism. The presence of higher-order regions may act as niduses of instability that can degenerate into chaotic fibrillation.

biophysics↗

bioRxiv2021

Weakly-Coupled Oscillators with Long-Distance Correlation as a Model of Human Atrial Fibrillation

I.Atrial Fibrillation (AF) is a chronic, progressive, and heterogeneous disease, which exhibits irregular and chaotic atrial electrical activity. The exact mechanisms of AF have remained elusive. The complexity of the atrial signals, irregular period, and the non-local nature of AF make it very difficult to characterize its spatiotemporal organization. This paper presents a set of data-processing tools to find and evaluate the intracardiac signals in AF based on synchronization theory. Specifically, a graph-theoretical algorithm is developed to prune spurious detections of atrial complexes (spikes). The processing pipeline was applied to 10 intracardiac recordings obtained during ablation procedures in patients with paroxysmal or persistent AF. The AF cases were classified into three main types. Type I (n=3) is defined as the presence of a single driver that dominates both atria and is consistent with the mother rotor hypothesis. The majority of the cases had more than one driver and were classified as types II (n=4) and III (n=3). The drivers, i.e., the interacting organized areas, in type II have significantly different peak frequencies and are only weakly coupled. The drivers in type III have close frequencies, are moderately interacting, and show evidence of transient intermittent phase-locking (intermittency). In addition, a long-distance correlation between channels from the left and right atria was observed. The theory of synchronization is a useful conceptual framework to process and analyze AF and can provide mechanistic insight into AF and the effect of various interventions.

biophysics↗

bioRxiv2020

Generation of Monophasic Action Potentials and Intermediate Forms

The Monophasic Action Potential (MAP) is a near replica of the transmembrane potential recorded when an electrode is pushed firmly against cardiac tissue. Despite its many practical uses, the mechanism of MAP signal generation and the reason it is so different from unipolar recordings is not completely known and is a matter of controversy. It is hypothesized that partial depolarization of the cells directly underneath the electrode contributes to the generation of MAP signals. In this paper, we describe a parametric, semi-quantitative method to generate realistic MAP and intermediate forms - multiphasic electrograms different from an ideal MAP - that does not require the partial depolarization hypothesis. The key ideas of our method are the formation of junctional spaces, i.e., electrically isolated pockets between the surface of an electrode and tissue, and the presence of a complex network of passive components that acts as a high-pass filter to distort the signal that reaches the recording amplifier. The passive network is formed by the interaction between the passive tissue properties and the double-layer capacitance of electrodes. We show that it is possible to generate different electrograms by the change of the model parameters and that both the MAP and intermediate forms reside on a continuum of signals. Our model helps to decipher the mechanisms of signal generation and can lead to a better design for electrodes, recording amplifiers, and experimental setups. SIGNIFICANCERecording the Monophasic Action Potential (MAP) is potentially very useful in both experimental and clinical cardiac electrophysiology and can provide valuable information about the repolarization phase of the action potential. However, despite its benefits, it currently has only a small and niche role. The main challenge is the technical difficulties of recording an ideal MAP. Our results provide a better understanding of the mechanisms of the generation of cardiac electrograms and may help to optimize experiments and improve tools to achieve the full potentials of recording the MAP signals.

biophysics↗

bioRxiv2018

Heterogeneity of the Frequency Domain Patterns in Persistent Atrial Fibrillation

BackgroundPersistent atrial fibrillation (AF) has remained a challenging clinical problem. The mechanisms of persistent AF are still subject to debate. Both a single mother-rotor with fibrillatory conduction and multiple meandering spiral waves have been proposed to explain persistent AF. Previous frequency domain studies have reported the presence of dominant frequency (DF) gradient (a marker of single mother-rotor) in paroxysmal, but not persistent AF.\n\nMethods and ResultsWe performed temporally-dense high-resolution frequency domain analysis of 10-40 minutes segments of intracardiac signals recorded in 24 patients undergoing ablation of persistent AF. We observed two predominant patterns. The expected signature of the mother-rotor mechanism was observed in 38% of the patients. The frequency pattern in 54% consisted of two or more distinct frequency peaks with no obvious gradient, which is consistent with multiple separate primary spiral waves in electrophysiologically heterogeneous areas of atria. The average measured number of rotors per case was 1.71 {+/-} 0.32, which provides a lower limit on the actual number of rotors. The single-zone pattern was exclusively seen in patients who were on a membrane-active antiarrhythmic medication at the time of ablation (P < 0.005).\n\nConclusionsAF is a heterogeneous disorder. High-frequency resolution analysis is a useful tool to detect the underlying mechanisms of AF and to classify it into patterns consistent with a single mother-rotor vs. multiple meandering wavelets.

biophysics↗