Development of an atrioventricular node inactivation technique to study electrical activity during atrial fibrillation in an experimental model

• Grant number: 23/12531-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2024
• End date: March 31, 2024
• Field of knowledge: Engineering - Biomedical Engineering - Bioengineering
• Principal Investigator: João Loures Salinet Júnior
• Grantee: Lizandra Gomes Souza
• Host Institution: Centro de Engenharia, Modelagem e Ciências Sociais Aplicadas (CECS). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated research grant: 18/25606-2 - Accurate mapping of cardiac fibrillation activity: an experimental contribution, AP.JP

Abstract

The heart is one of the main organs, being responsible for effectively pumping blood throughout the human body. The heart is made up of four chambers, the upper ones called atria and the lower ones called ventricles. Its contraction is synchronous, starting in the right atrium through the electrical depolarization of the pacemaker cells and spreading to other areas of the atria up to the atrioventricular (AV) node. Depolarization of the ventricles begins through the right and left branches towards their base, extending to the Purkinje fibers.The propagation of these action potentials (APs) to the rest of the heart is the result of complex intracellular mechanisms involving exchange of ions and intracellular molecules through various ion channels and transporters. The sum of the heart's APs allows the construction of the ECG signal, formed by P waves (depolarization of the atria), QRS (depolarization of the ventricles) and T (repolarization of the ventricles). Differences between APs may be a consequence of changes in the size, shape and structure of heart cells, contributing to changes in cell conductivity.Factors such as geneticSs, aging, poor eating habits, sedentary lifestyle and excessive alcohol use imply changes in the anatomy and physiology of the heart, which may favor the emergence of cardiac arrhythmias. Heart complications affect the quality of life of these individuals and generate high costs for treatment by the public authorities.Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice, affecting 1% to 2% of the world population. Its prevalence increases with age (8% for octogenarians), and is generally associated with structural heart diseases, causing hemodynamic damage and thromboembolic complications with major economic implications. This disorder has high morbidity and mortality, and has become a chronic non-infectious cardiovascular epidemic with a large consumption of health resources.AF is characterized by the collapse of organized cardiac electrical activity - responsible for the periodic and synchronized pumping of the atria - into disorganized and self-sustaining electrical activation patterns, a condition resulting from multiple causes and can occur in young patients without demonstrable structural heart disease. As a consequence of this reduction in the effectiveness of atrial systolic and diastolic functions, there is a significant decrease in cardiac output, increasing the chances of thromboembolic phenomena, heart failure and sudden arrhythmic death.Non-invasively recorded cardiac signals from the chest (i.e. electrocardiograms) and intracardiac signals have been widely used in AF studies with the aim of understanding atrial electrical behavior to improve the effectiveness of interventional ablation treatment, but the presence of ventricular activity in these signals has hampered analysis with the possibility of distorting results. It is important to study atrial activity without the influence of ventricular activity to improve understanding of the genesis and maintenance of AF. Because atrial activity and ventricular activity overlap in the time and frequency domains within the relevant AF frequency range (3 Hz to 15 Hz), the use of linear filtering solutions is ineffective in separating them and isolation of atrial activity is difficult. Therefore, experimental interventional research that favors the inactivation of the AV node will favor the non-propagation of electrical activity to the ventricles, consequently avoiding the influence of ventricular activity on atrial activity.An in situ experimental model of AF induced by electrical stimulation in isolated rabbit hearts to improve the diagnosis of cardiac electrical activity of AF is developed. During the experiment, before AF induction by electrical stimulation, the scholarship candidate will inactivate the AV node, through cauterization or drugs.