Influence of autonomic nervous system in the inducibility of atrial fibrillation.

Cílem této práce je zjištění změn předcházejícím fibrilaci síní. Pozorována je rovnováha mezi sympatikem a parasympatikem. Do experimentu výzkumného ústavu Cleavlendské kliniky bylo zapojeno šest psů různých ras. Signály EKG byly získány Holterovským 24hodinovým monitorováním. Pomocí 40 vysokofrekvenčních impulsů (TI) byla každých 30 minut vyvolávána AF. Z 24hodinového signálu byly extrahovány kratší epizody. Každá z těchto epizod obsahovala 10 minut předcházejících TI a 3 minuty následující po TI. Desetiminutové epizody byly zpracovány automaticky, byly detekovány QRS komplexy a RR intervaly a vypočteny HRV parametry. Přítomnost a délka trvání AF byly zjištěny manuálně z tříminutových intervalů následujících po TI. Byla-li vyvolána AF o délce trvání kratší než 30 sekund došlo ve srovnání s epizodami bez výskytu AF k významným změnám tří HRV parametrů. HF parametr poklesl pro epizody s výskytem AF. LF parametr byl naopak vyšší v epizodách s AF. Pro AF delší než 30 sekund nebyly významné změny pozorovány. Změny v epizodách s krátkou AF mohly být způsobeny změnami vlivu sympatiku a parasympatiku. Ke vzniku dlouhých AF je pravděpodobně zapotřebí i jiného vlivu, který nemusí nutně souviset s nervovým systémem. K dalším analýzám je zapotřebí většího množství signálů.The aim of this study is to investigate changes in sympatho-vagal balance before the initiation of AF. Six mongrel dogs from the Cleveland Clinic foundation were included in this study. ECG was recorded for 24 hours using telemetric Holter monitoring. AF was periodically induced every 30 min. by applying brief bursts of 40 high-frequency atrial train impulses (TI). From the 24 hours signals' traces shorter data episodes were extracted. Each episode consisted of 10 minutes preceding the atrial burst, and 3 minutes following the (TI). The 10 minutes episodes were processed automatically to determine the QRS complexes and RR intervals, and to calculate the HRV parameters. The presence and the duration of AF were determined by manual examination in each of the 3 minutes intervals following the delivery of TI. When the AF was generated, but episodes of AF were shorter than 30 seconds, three HRV parameters were significantly different than when AF was not generated. The HF component was lower in episodes that generated AF. The LF component was higher in episodes that generated AF. No significant differences were found when episodes of AF were longer than 30 seconds. Short episodes of AF could be generated when a certain disorder between sympathetic and parasympathetic tone is present. However in order to be able to generate longer AF episodes it is necessary another component not necessary related to the nervous system. Further analysis with a higher number of dogs should be needed.

Advances in computational modelling for personalised medicine after myocardial infarction

Myocardial infarction (MI) is a leading cause of premature morbidity and mortality worldwide. Determining which patients will experience heart failure and sudden cardiac death after an acute MI is notoriously difficult for clinicians. The extent of heart damage after an acute MI is informed by cardiac imaging, typically using echocardiography or sometimes, cardiac magnetic resonance (CMR). These scans provide complex data sets that are only partially exploited by clinicians in daily practice, implying potential for improved risk assessment. Computational modelling of left ventricular (LV) function can bridge the gap towards personalised medicine using cardiac imaging in patients with post-MI. Several novel biomechanical parameters have theoretical prognostic value and may be useful to reflect the biomechanical effects of novel preventive therapy for adverse remodelling post-MI. These parameters include myocardial contractility (regional and global), stiffness and stress. Further, the parameters can be delineated spatially to correspond with infarct pathology and the remote zone. While these parameters hold promise, there are challenges for translating MI modelling into clinical practice, including model uncertainty, validation and verification, as well as time-efficient processing. More research is needed to (1) simplify imaging with CMR in patients with post-MI, while preserving diagnostic accuracy and patient tolerance (2) to assess and validate novel biomechanical parameters against established prognostic biomarkers, such as LV ejection fraction and infarct size. Accessible software packages with minimal user interaction are also needed. Translating benefits to patients will be achieved through a multidisciplinary approach including clinicians, mathematicians, statisticians and industry partners

Competing mechanisms of stress-assisted diffusivity and stretch-activated currents in cardiac electromechanics

We numerically investigate the role of mechanical stress in modifying the conductivity properties of the cardiac tissue and its impact in computational models for cardiac electromechanics. We follow a theoretical framework recently proposed in [Cherubini, Filippi, Gizzi, Ruiz-Baier, JTB 2017], in the context of general reaction-diffusion-mechanics systems using multiphysics continuum mechanics and finite elasticity. In the present study, the adapted models are compared against preliminary experimental data of pig right ventricle fluorescence optical mapping. These data contribute to the characterization of the observed inhomogeneity and anisotropy properties that result from mechanical deformation. Our novel approach simultaneously incorporates two mechanisms for mechano-electric feedback (MEF): stretch-activated currents (SAC) and stress-assisted diffusion (SAD); and we also identify their influence into the nonlinear spatiotemporal dynamics. It is found that i) only specific combinations of the two MEF effects allow proper conduction velocity measurement; ii) expected heterogeneities and anisotropies are obtained via the novel stress-assisted diffusion mechanisms; iii) spiral wave meandering and drifting is highly mediated by the applied mechanical loading. We provide an analysis of the intrinsic structure of the nonlinear coupling using computational tests, conducted using a finite element method. In particular, we compare static and dynamic deformation regimes in the onset of cardiac arrhythmias and address other potential biomedical applications

Regulated Inositol‐Requiring Protein 1‐Dependent Decay as a Mechanism of Corin RNA and Protein Deficiency in Advanced Human Systolic Heart Failure

BACKGROUND: The compensatory actions of the endogenous natriuretic peptide system require adequate processing of natriuretic peptide pro‐hormones into biologically active, carboxyl‐terminal fragments. Natriuretic peptide pro‐peptide processing is accomplished by corin, a transmembrane serine protease expressed by cardiomyocytes. Brain natriuretic peptide (BNP) processing is inadequate in advanced heart failure and is independently associated with adverse outcomes; however, the molecular mechanisms causing impaired BNP processing are not understood. We hypothesized that the development of endoplasmic reticulum stress in cardiomyocytes in advanced heart failure triggers inositol‐requiring protein 1 (IRE1)‐dependent corin mRNA decay, which would favor a molecular substrate favoring impaired natriuretic peptide pro‐peptide processing. METHODS AND RESULTS: Two independent samples of hearts obtained from patients with advanced heart failure at transplant demonstrated that corin RNA was reduced as Atrial natriuretic peptide (ANP)/BNP RNA increased. Increases in spliced X‐box protein 1, a marker for IRE1‐endoribonuclease activity, were associated with decreased corin RNA. Moreover, ≈50% of the hearts demonstrated significant reductions in corin RNA and protein as compared to the nonfailing control sample. In vitro experiments demonstrated that induction of endoplasmic reticulum stress in cultured cardiomyocytes with thapsigargin activated IRE1s endoribonuclease activity and time‐dependent reductions in corin mRNA. In HL‐1 cells, overexpression of IRE1 activated IRE1 endoribonuclease activity and caused corin mRNA decay, whereas IRE1‐RNA interference with shRNA attenuated corin mRNA decay after induction of endoplasmic reticulum stress with thapsigargin. Pre‐treatment of cells with Actinomycin D to inhibit transcription did not alter the magnitude or time course of thapsigargin‐induced corin mRNA decline, supporting the hypothesis that this was the result of IRE1‐mediated corin mRNA degradation. CONCLUSIONS: These data support the hypothesis that endoplasmic reticulum stress‐mediated, IRE1‐dependent targeted corin mRNA decay is a mechanism leading to corin mRNA resulting in corresponding corin protein deficiency may contribute to the pathophysiology of impaired natriuretic peptide pro‐hormone processing in humans processing in humans with advanced systolic heart failure

New Cardiovascular Indices Based on a Nonlinear Spectral Analysis of Arterial Blood Pressure Waveforms

A new method for analyzing arterial blood pressure is presented in this report. The technique is based on the scattering transform and consists in solving the spectral problem associated to a one-dimensional Schr\"odinger operator with a potential depending linearly upon the pressure. This potential is then expressed with the discrete spectrum which includes negative eigenvalues and corresponds to the interacting components of an N-soliton. The approach is similar to a nonlinear Fourier transform where the solitons play the role of sine and cosine components. The method provides new cardiovascular indices that seem to contain relevant physiological information. We first show how to use this approach to decompose the arterial blood pressure pulse into elementary waves and to reconstruct it or to separate its systolic and diastolic phases. Then we analyse the parameters computed from this technique in two physiological conditions, the head-up 60 degrees tilt test and the isometric handgrip test, widely used for studying short term cardiovascular control. Promising results are obtained