Sex- and Age-Related Features of Interrelations Between Structural and Functional Parameters of the Heart in Junior Speed Skaters

Success of adaptive changes in young athletes in response to training and competition loads is predicted on the basis of a comprehensive assessment of quantitative and qualitative parameters of the state of critical body systems, primarily, the cardiovascular system. The aim of this paper was to determine sex- and age-related features of the morphofunctional parameters of the heart in young skaters and to identify the relationships that determine their adaptation to speed skating. Materials and methods. The research (with informed consent) included 49 athletes of both sexes with the rank of the First-Class Sportsman. The subjects were divided by age and sex into four subgroups: boys aged 13–15 and 16–18 years; girls aged 13–15 and 16–18 years. We performed electrocardiogram (ECG) recording and echocardiographic examination at rest in line with the existing protocols. Results. According to the screening of intra-system correlations between ECG and echocardiography contour analysis parameters, the following proved to be of prognostic significance: QT interval duration, heart rate and alpha angle for girls aged 13–15 years; duration of atrial excitation and pulmonary artery diameter for boys aged 13–15 years; ejection fraction and cardiac cycle duration for girls aged 16–18 years; duration of atrial excitation, which has four correlations with echocardiographic parameters, for boys aged 16–18 years. The revealed features of the structure of intra-system relationships between 21 morphofunctional parameters of the cardiovascular system are determined in the first age group (13–15 years) by athlete’s sex, while in the second age group (16–18 years) by sex and type of sport. For citation: Yarysheva V.B., Shibkova D.Z., Bayguzhin P.A., Erlikh V.V. Sex- and Age-Related Features of Interrelations Between Structural and Functional Parameters of the Heart in Junior Speed Skaters. Journal of Medical and Biological Research, 2021, vol. 9, no. 4, pp. 405–416. DOI: 10.37482/2687-1491-Z078

Abstract P498: Polycystin-1 Regulates Excitation-contraction Coupling In Atrial Cardiomyocytes

Patients with Autosomal Dominant Polycystic Kidney disease (ADPKD) have multiple cardiovascular manifestations, including increased susceptibility to arrhythmias. Mutations in polycystin-1 (PC1) encoding gene accounts for 85% cases of ADPKD, whereas mutations in polycystin-2 (PC2) only accounts for 15%. In kidney cells, PC1 interacts with PC2 to form a protein complex at the primary cilia to regulate calcium influx via PC2. However, cardiomyocytes are non-ciliated cells and the role of both PC1 and PC2 in atrial cardiomyocytes remains unknown. We have previously demonstrated that PC1 regulates action potentials and calcium handling to fine-tune ventricular cardiomyocyte contraction. Here, we hypothesize that PC1 regulates action potentials and calcium handling in atrial cardiomyocytes independent of PC2 actions. To test this hypothesis, we differentiated human induced pluripotent stem cells (iPSC) into atrial cardiomyocytes (iPSC-aCM) using previously published protocols. To determine the contribution of PC1/PC2 in atrial excitation-contraction coupling, protein expression was knocked down utilizing specific siRNA constructs, for each protein, or a universal control siRNA transfected using lipofectamine RNAiMAX. We measured action potentials using the potentiometric dye FluoVolt and intracellular calcium with Fura-2 AM or Fluo-4. Changes in fluorescence were monitored using a multiwavelength IonOptix system. iPSC-aCM were paced at 2 Hz to synchronize the beating pattern using field electrical stimulation. Our data shows that PC1 ablation significantly decreased action potential duration at 50% and 80% of repolarization, by 24% and 23%, respectively. Moreover, we observed that PC1 knockdown significantly reduced calcium transient amplitude elicited by field electrical stimulation without changes in calcium transient decay. Interestingly, PC2 knockdown did not modify calcium transients in atrial cardiomyocytes (iPSC-aCM). Our data suggest that PC1 regulates atrial excitation-contraction coupling independent of PC2 actions. This study warrants further investigation into atrial dysfunction in ADPKD patients with PC1 mutations.

A Computer Simulation Research of Two Types of Cardiac Physiological Pacing

This manuscript adopted the cardiac modeling and simulation method to study the problems of physiological pacing in clinical application. A multiscale rabbit ventricular electrophysiological model was constructed. We simulated His-bundle pacing (HBP) treatment for left bundle branch block (LBBB) and atrioventricular block (AVB), and left bundle branch pacing (LBBP) treatment for LBBB by setting various moments of the stimulus. The synthetic ECGs and detailed electrical activities were analyzed. Our electrophysiological model accurately simulated the normal state, HBP, and LBBP. The synthetic ECG showed that QRS duration was narrowed by 30% after HBP correction for LBBB. For LBBB correction with LBBP, the synthetic ECGs of LBBP starting before 30 ms (if the end of atrial excitation is set as 0 ms) presented right bundle branch block (RBBB), and those of LBBP starting at 30–38 ms were synchronous, while those of LBBP starting after 42 ms possessed LBBB morphologies. The best pacing results were obtained when LBBP started at 34 ms. This manuscript verified the feasibility of the constructed ventricular model, and studied the physiological pacing mechanism. The results showed that HBP realized correction for AVB and high LBBB. The performance of LBBP can be improved by applying the stimulus within a specific period of time (0–8 ms) after atrial excitation.

Effect of carvedilol on atrial excitation-contraction coupling, Ca2+ release, and arrhythmogenicity

Here we show that the clinically widely used β-blocker carvedilol has profound effects on Ca2+ signaling and ion currents, but also antiarrhythmic effects in adult atrial myocytes. Carvedilol inhibits sodium and calcium currents and leads to failure of ECC but also prevents spontaneous Ca2+ release from cellular sarcoplasmic reticulum (SR) Ca2+ stores in form of arrhythmogenic Ca2+ waves. The antiarrhythmic effect occurs by carvedilol acting directly on the SR ryanodine receptor Ca2+ release channel.

Interactive visualization of cardiac anatomy and atrial excitation for medical diagnosis and research

State of the art biomedical engineering allows for acquiring enormous amounts of intracardiac data to aid diagnosis and treatment of cardiac arrhythmias. Modern catheters, which are used to acquire electrical information from within the heart, are capable of recording up to 64 channels simultaneously. The software available for data analysis, however, does not provide adequate performance to neither analyze nor visualize the acquired information in an appropriate manner. We present a software package that fascilitates interdisciplinary collaborations between engineers and physicians to adress open questions about pathophysiological mechanisms using data from everyday electrophysiogical studies. Therefore, a package has been compiled that enables algorithm development using MATLAB and subsequent visualization using the VTK C++ class libraries. The resulting application KaPAVIE, which is presented in this paper, is designed to meet the requirements from the clinical side and has been successfully applied in the clinical environment.

Abstract 12559: Rapid Atrial Pacing Augments Fibrinogen Expression With Activation of IL-6/STAT3 Signaling Pathway in the Rat Liver

Introduction: Atrial fibrillation (AF) activates coagulation system leading to hypercoagulation of the blood. However, it is still unknown whether rapid atrial excitation per se affects gene expression remotely in the liver, the major source of coagulation factors and other prothrombotic molecules. Methods and Results: The AF model was created by rapid atrial pacing at the frequency of 1200 bpm in anesthetized 10-week-old Sprague-Dawley rats. The livers and peripheral blood cells were collected and analyzed after the pacing of 12 hours. Sham-operated rats underwent the identical procedure without electrical stimulation. DNA microarray revealed marked changes in hepatic gene expression after 12 hours atrial pacing. Hierarchical clustering with 13871 filtered genes or genes related to coagulation including fibrinogen, demonstrated clusters for the pacing or sham. The quantitative RT-PCR focused on prothrombotic molecules revealed that rapid atrial pacing significantly augmented the hepatic mRNA expressions of fibrinogen α, β, γ-chain, prothrombin, antithrombin-III, plasminogen, and coagulation factor X. The increase of fibrinogen protein in the liver was also confirmed by Western blotting (Figure A). We further investigated the mechanism of enhanced fibrinogen production and identified increased IL-6 mRNA expression in the peripheral blood cells by rapid atrial pacing (Figure B). IL-6 was also prominent in CD11b positive cells infiltrated in the liver, and possibly promoted STAT3 phosphorylation in the nuclei of hepatocytes (Figure C). Conclusions: The rapid atrial excitation mimicking paroxysmal AF altered the hepatic gene expressions of prothrombotic molecules. Increased fibrinogen expression in the liver was accompanied by activation of IL-6/STAT3 signaling pathway in the peripheral blood and the liver. These findings might imply the cardio-hepatic interaction in AF and provide new insight into the prevention of AF-related thromboembolism.