Evaluation of the Complexity of Myocardial Activation During Ventricular Fibrillation. An Experimental Study

A B S T R A C T Introduction and objectives: An experimental model is used to analyze the characteristics of ventricular fibrillation in situations of variable complexity, establishing relationships among the data produced by different methods for analyzing the arrhythmia. Methods: In 27 isolated rabbit heart preparations studied under the action of drugs (propranolol and KB-R7943) or physical procedures (stretching) that produce different degrees of change in the complexity of myocardial activation during ventricular fibrillation, use was made of spectral, morphological, and mapping techniques to process the recordings obtained with epicardial multielectrodes. Results: The complexity of ve…

PPARγ as an indicator of vascular function in an experimental model of metabolic syndrome in rabbits

Abstract Background and aims Underlying mechanisms associated with vascular dysfunction in metabolic syndrome (MetS) remain unclear and can even vary from one vascular bed to another. Methods In this study, MetS was induced by a high-fat, high-sucrose diet, and after 28 weeks, aorta and renal arteries were removed and used for isometric recording of tension in organ baths, protein expression by Western blot, and histological analysis to assess the presence of atherosclerosis. Results MetS induced a mild hypertension, pre-diabetes, central obesity and dyslipidaemia. Our results indicated that MetS did not change the contractile response in either the aorta or renal artery. Conversely, vasodi…

Diet-Induced Rabbit Models for the Study of Metabolic Syndrome

Simple Summary In recent years, obesity and metabolic syndrome (MetS) have become more prevalent owing to increased unhealthy habits and sedentary lifestyles, becoming public health problems. Experimental studies have allowed us to explore the mechanisms underlying the pathophysiological processes related to MetS. Several research protocols can be carried out with minimal staff, maintenance, and resources in animals such as rabbits. High-fat diets enriched with other components, mainly cholesterol and sugars, result in the rapid development of hypercholesterolemia and vascular alterations as a response to dietary manipulation. Furthermore, other experimental models, including transgenic rab…

P312The selective late sodium current inhibitor eleclazine attenuates ventricular fibrillation spectral characteristics modifications produced by acute myocardial stretch

Nerves projecting from the intrinsic cardiac ganglia of the pulmonary veins modulate sinoatrial node pacemaker function

Rationale: Autonomic nerves from sinoatrial node (SAN) ganglia are known to regulate SAN function. However, it is unclear whether remote pulmonary vein ganglia (PVG) also modulate SAN pacemaker rhythm. Objective: To investigate whether in the mouse heart PVG modulate SAN function. Methods and Results: In hearts from 45 C57BL and 7 Connexin40+/GFP mice, we used tyrosine-hydroxylase (TH) and choline-acetyltransferase (ChAT) immunofluorescence labeling to characterize adrenergic and cholinergic elements, repectively, within the PVG and SAN. PVG project postganglionic nerves to the SAN. TH and ChAT stained nerves, enter the SAN as an extensive, dense mesh-like neural network. Neurons in PVG are…

P267Myocardial electrophysiological effects mediated by KATP channels: controversial aspects about their involvement in the protection by chronic exercise

P1602Basic electrophysiological modifications induced by carvedilol in unstrectched and stretched ventricular myocardium

Abstract Background Acute regional ventricular stretch (ARVS) is a pathophysiologic event that may occur in certain situations, originating arrhythmogenic effects through the mechanoelectrical feedback. Mechanical effects of stretch originate calcium-related changes as sarcoplasmic recticulum Ca2+ overload that can trigger Ca2+ diastolic leaks (store-overload-induced Ca2+ release, SOICR), mediated by the cardiac ryanodine receptor (RyR2). SOICR seems to be implicated in the mechanisms underlying stretch-induced arrhythmias. Carvedilol can inhibit the overload of Ca2+ through blocking of beta-adrenergic receptors, and also suppress the release of Ca2+ induced by the SOICR. Purpose The aim of…

Development and Long-Term Follow-Up of an Experimental Model of Myocardial Infarction in Rabbits

Simple Summary Ischemic heart disease is one of the leading causes of death. A series of processes occur during acute myocardial infarction that contribute to the development of ventricular dysfunction, with subsequent heart failure and ventricular arrhythmias, which account for most episodes of sudden cardiac death in these patients. These complications are associated with the adverse cardiac remodeling that occurs during the healing process following an acute episode. The remodeling causes the appearance of a substrate that can trigger life-threatening arrhythmias, such as tachycardia and/or ventricular fibrillation. The development of experimental models for analyzing the basic mechanism…

Endurance training increases ventricular refractoriness and wavelength of the cardiac impulse without participation of parasympathetic postganglionic neurons. A study in isolated rabbit heart

Abstract Background Endurance physical training plays a protective role in against ventricular fibrillation (VF), but the exact underlying mechanisms are not completely understood. It is well-known that modifications in myocardial ventricular properties such as refractoriness, conduction velocity and wavelength are key in the initiation and maintenance of VF; furthermore, vagus nerve stimulation has prophylactic effects on malignant arrhythmias and VF. On the other hand, parasympathetic nervous system activity is increased in trained individuals, which in turn affects different ventricular electrophysiological properties. We hypothesized that physical training increases conduction velocity …

P314Modifications of atrial refractoriness produced in an experimental rabbit model of diet-induced metabolic syndrome

P3492Carvedilol and its analogue VK-II-86 attenuate stretch-induced manifestations of mechanoelectric feedback

Abstract Background Mechanical stretch modifies Ca2+ handling and myocardial electrophysiology, favoring arrhythmogenesis. The store-overload-induced Ca2+ release (SOICR) through the ryanodine receptor (RyR2) seems to be implicated in this deleterious effect. Carvedilol and its analogue VK-II-86 (which does not have significant beta-blocking effects) suppress SOCIR by directly reducing the open duration of the cardiac RyR2, and could modulate calcium-related changes produced by myocardial stretch. Purpose The aim of this study was to investigate, by the ventricular fibrillation (VF) spectral analysis, whether carvedilol and VK-II-86 prevents stretch-induced arrhythmogenic effects. Methods T…

Effect of chronic exercise on myocardial electrophysiological heterogeneity and stability. Role of intrinsic cholinergic neurons: A study in the isolated rabbit heart

[EN] A study has been made of the effect of chronic exercise on myocardial electrophysiological heterogeneity and stability, as well as of the role of cholinergic neurons in these changes. Determinations in hearts from untrained and trained rabbits on a treadmill were performed. The hearts were isolated and perfused. A pacing electrode and a recording multielectrode were located in the left ventricle. The parameters determined during induced VF, before and after atropine (1 mu M), were: fibrillatory cycle length (VV), ventricular functional refractory period (FRPVF), normalized energy (NE) of the fibrillatory signal and its coefficient of variation (CV), and electrical ventricular activatio…

CaMKII inhibition reduces electrical activation heterogeneities caused by mechanical stretch in the myocardium

Abstract Introduction Ca2+/calmodulin-dependant protein kinase II (CaMKII) activity in cardiomyocytes plays a crucial role in their contractility. Increased CaMKII signalling has been associated with mechanical stretch, often caused in the border zone of myocardial infarction. CaMKII upregulation causes a mishandling of intracellular calcium, a precursor of multiple pro-arrhythmic mechanisms, such as early afterdepolarisations. Purpose In this study, we aim to quantify the effects of KN-93 -a CaMKII inhibitor- on wave dynamics, in order to investigate its effectiveness as an anti-arrhythmic agent. Methods An isolated Langendorff model was constructed based on rabbit hearts (n=18) and poster…

Altered atrial restitution dynamics and refractoriness in metabolic syndrome due to up-regulation of potassium repolarizing currents increases susceptibility to atrial fibrillation

Abstract Background Metabolic alterations, such as Metabolic Syndrome (MS), describe an association of factors including diabetes, hypertension, obesity and dyslipidemia, linked to higher risk and prevalence of overall cardiovascular disease, arrhythmogenesis and sudden cardiac death. Obese and diabetic patients have shown an increased risk for developing atrial fibrillation (AF). However, underlying mechanisms are not understood. Purpose To study the effects of MS and obesity remodeling in atrial restitution dynamics, frequency-dependent adaptation, refractoriness and its potential susceptibility to AF. Methods Electrophysiological experimental data from High-fat (HF-O, standard rabbit cho…

Simultaneous atrial and ventricular restitution and fibrillation analyses using a low-cost scalable panoramic whole-heart optical mapping configuration for whole-heart imaging of translational models

Abstract Introduction Optical mapping (OM) is the primary method for imaging electrophysiologically relevant parameters from the outer surface of Langendorff-perfused hearts. However, current panoramic OM systems are financially challenging, require multiple sensors to map wide areas of the surface with overlapping regions and missing areas of interest due to the intrinsic shape of the heart. We proposed different panoramic configurations to dynamically characterize atrial and ventricular function during arrhythmia and, in presence of a coronary occlusion. Methods We devised both a multi-sensor and a single sensor system integrated with the perfusion circuit comprising sensor elements, a co…

Dual-sided Mapping During Global Stretch Using a Custom Miniaturized Endocardial Balloon with a Multipurpose Multichannel Acquisition System for Preclinical Electrophysiological Studies

Acute regional myocardial stretch (STR) is known to induce myocardial electrophysiological modifications via mechano-electric feedback (MEF), including abnormal repolarization, premature excitation and increased complexity of activation leading to the initiation, maintenance and acceleration of arrhythmic events. Due to technical limitations little is known about intramural and endo-epicardial (ENDO-EPI) phenomena during these events. Understanding ENDO-EPI modifications produced by STR through MEF may require a dual-sided approach to simultaneously correlate macroscopic surface modifications and their independent or interconnected components. For that purpose, we optically mapped (OM) the …

An Experimental Model of Diet-Induced Metabolic Syndrome in Rabbit: Methodological Considerations, Development, and Assessment

In recent years, obesity and metabolic syndrome (MetS) have become a growing problem for public health and clinical practice, given their increased prevalence due to the rise of sedentary lifestyles and unhealthy eating habits. Thanks to animal models, basic research can investigate the mechanisms underlying pathological processes such as MetS. Here, we describe the methods used to develop an experimental rabbit model of diet-induced MetS and its assessment. After a period of acclimation, animals are fed a high-fat (10% hydrogenated coconut oil and 5% lard), high-sucrose (15% sucrose dissolved in water) diet for 28 weeks. During this period, several experimental procedures were performed to…

Estudio experimental de los efectos de EIPA, losartán y BQ-123 sobre las modificaciones electrofisiológicas inducidas por el estiramiento miocárdico

Resumen Introduccion y objetivos Se han implicado diversos mecanismos en la respuesta mecanica al estiramiento miocardico, que incluyen la activacion del intercambiador Na+/H+ por acciones autocrinas y paracrinas. Se estudia la participacion de estos mecanismos en las respuestas electrofisiologicas al estiramiento agudo miocardico mediante el analisis de los cambios inducidos con farmacos. Metodos Se analizan las modificaciones de la fibrilacion ventricular inducidas por el estiramiento agudo miocardico en corazones de conejo aislados y perfundidos utilizando electrodos multiples epicardicos y tecnicas cartograficas. Se estudian 4 series: control (n = 9); durante la perfusion del antagonist…

P330Modifications of short-term heart rate varibility and intrinsic pacemaker variability in an experimental model of metabolic syndrome

Diet-Induced Metabolic Syndrome Reduced Heart Rate Variability and Increased Irregularity and Complexity of Short-Term RR Time Series in Rabbits.

Simple Summary In recent years, obesity and metabolic syndrome (MetS) have become more prevalent, owing to increased unhealthy habits and sedentary lifestyles becoming public health problems. Both conditions are linked with a higher prevalence of sudden cardiac death (SCD), but the exact mechanisms are not known. An autonomic nervous system imbalance can produce atrial and ventricular arrhythmias, which cause SCD, and this can be quantified by analyzing heart rate variability (HRV). We investigated HRV using time-domain, frequency-domain and nonlinear analyses during the development of MetS in rabbits and found HRV modifications that could be associated with the higher prevalence of SCD in …

Development and characterization of an experimental model of diet-induced metabolic syndrome in rabbit

Metabolic syndrome (MetS) has become one of the main concerns for public health because of its link to cardiovascular disease. Murine models have been used to study the effect of MetS on the cardiovascular system, but they have limitations for studying cardiac electrophysiology. In contrast, the rabbit cardiac electrophysiology is similar to human, but a detailed characterization of the different components of MetS in this animal is still needed. Our objective was to develop and characterize a diet-induced experimental model of MetS that allows the study of cardiovascular remodeling and arrhythmogenesis. Male NZW rabbits were assigned to control (n = 15) or MetS group (n = 16), fed during 2…

Determination of the Optimal Saddle Height for Leisure Cycling (P188)

Several studies have been done on road racing cycling and triathlon to determine the optimal saddle height (LINF) in terms of efficiency. However, cycling is becoming nowadays not only a popular sport but also a mass mean of transport were comfort takes priority over efficiency. The aim of this study is to determine an optimal saddle height (LINF) to improve comfort in leisure cycling. Five male subjects (height mean=172.2 cm, std=1.34 cm; crotch height mean=81.25cm, std=0.88cm) tested 9 prototypes of the company ORBEA with 3 levels of LINF. The test consisted in one hour cycling in lab conditions and four different techniques were used to evaluate the LINF: 3-D movement analysis was used t…

Time and frequency domain analysis of long-term heart rate variability in an experimental model of diet-induced metabolic syndrome

Abstract Background Metabolic syndrome (MetS) is defined as the set of at least three of the following conditions: central obesity, elevation of triglycerides, decreased in high-density lipoproteins, systemic hypertension and glucose intolerance. MetS is linked with a high prevalence of cardiovascular disease, including sudden cardiac death and atrial arrhythmias, which may be a consequence of changes related to the structure, function and autonomic control of the heart. One of the underlying mechanisms responsible could be the alteration of sinus node automaticity. Heart rate variability (HRV) analysis is a useful non-invasive tool for evaluating alterations in neural control of cardiac au…

Ventricular remodelling in rabbits with sustained high-fat diet.

Aim Excess weight gain and obesity are one of the most serious health problems in the western societies. These conditions enhance risk of cardiac disease and have been linked with increased prevalence for cardiac arrhythmias and sudden death. Our goal was to study the ventricular remodelling occurring in rabbits fed with high-fat diet (HFD) and its potential arrhythmogenic mechanisms. Methods We used 15 NZW rabbits that were randomly assigned to a control (n = 7) or HFD group (n = 8) for 18 weeks. In vivo studies included blood glucose, electrocardiographic, and echocardiographic measurements. Optical mapping was performed in Langendorff-perfused isolated hearts. Results Body weight (3.69 ±…

A Single-sensor High-resolution Panoramic Optical Mapping Configuration for Simultaneous Non-overlapped Complete Atrial and Ventricular Parametric Imaging

Nowadays optical mapping (OM) is the primary method for imaging electrophysiologically relevant parameters from the outer surface of Langendorff-perfused hearts. This technique has become essential for comprehensively understanding mechanisms of cardiac propagation during physiological activation, arrhythmia, and therapeutic antiarrhythmic interventions in translational hearts. Panoramic whole heart optical mapping systems, using either multiple cameras, plane mirrors or a combination of both, have been developed to overcome intrinsic visualization limitations to traditional single-sensor designs. However current panoramic OM systems are financially challenging for physiology and engineerin…

Heterogeneidades inducidas en el intervalo QT mediante enfriamiento/calentamiento epicárdico local. Estudio experimental

Resumen Introduccion y objetivos La duracion anormal del intervalo QT o su dispersion se han asociado con un incremento en el riesgo de arritmias ventriculares. Se analiza el posible efecto arritmogenico de sus variaciones inducidas mediante enfriamiento y calentamiento local epicardico. Metodos En 10 corazones aislados de conejo, se modifico escalonadamente la temperatura de una region epicardica del ventriculo izquierdo (22 a 42 ° C ), registrando simultaneamente los electrogramas en dicha zona y en otra del mismo ventriculo. En ritmo sinusal, se determino el QT y el intervalo de recuperacion de la activacion y, mediante estimulacion programada, la velocidad de conduccion y la induccion d…

Effect of Kinesio Taping and balance exercises on postural control in amateur soccer players: A randomised control trial

The objective of this study was to determine the effect of Kinesio Taping (KT), alone or together with balance exercises (BE), on parameters related to postural control, such as dynamic balance, static balance and flexibility. Forty-four male amateur soccer players (mean age 24.45 (4.79) years) were randomly allocated to 3 groups: KT+BE that received KT and BE (n = 16); KT

Experimental Study of the Effects of EIPA, Losartan, and BQ-123 on Electrophysiological Changes Induced by Myocardial Stretch

[ES] Introducción y objetivos Se han implicado diversos mecanismos en la respuesta mecánica al estiramiento miocárdico, que incluyen la activación del intercambiador Na+/H+ por acciones autocrinas y paracrinas. Se estudia la participación de estos mecanismos en las respuestas electrofisiológicas al estiramiento agudo miocárdico mediante el análisis de los cambios inducidos con fármacos. Métodos Se analizan las modificaciones de la fibrilación ventricular inducidas por el estiramiento agudo miocárdico en corazones de conejo aislados y perfundidos utilizando electrodos múltiples epicárdicos y técnicas cartográficas. Se estudian 4 series: control (n = 9); durante la perfusión del antagonista d…

Evaluación de la complejidad de la activación miocárdica durante la fibrilación ventricular. Estudio experimental

Resumen Introduccion y objetivos Analizar en un modelo experimental las caracteristicas de la fibrilacion ventricular en situaciones con distintos grados de complejidad y establecer la relacion existente entre los datos aportados por distintos metodos de analisis de la arritmia. Metodos En 27 preparaciones de corazon aislado de conejo estudiadas bajo la accion de farmacos (propranolol y KB-R7943) o procedimientos fisicos (estiramiento) que causan distintos grados de variacion de la complejidad de la activacion miocardica durante la arritmia, se han utilizado tecnicas espectrales, morfologicas y cartograficas para procesar los registros obtenidos con multielectrodos epicardicos. Resultados L…

Exercise Training Protocols in Rabbits Applied in Cardiovascular Research

Simple Summary Several animal models have been used to understand the physiological adaptations produced by exercise training in the healthy and diseased cardiovascular system. Among those, the protocols for acute and chronic exercise in rabbits present several advantages compared to other large animal models. In addition, the rabbit model has important physiological similarities with humans. On the other hand, the design of the training protocol is a key factor to induce the physiological adaptations. Here, we review the different training protocols used in rabbits and the different physiological adaptations produced in the cardiovascular system, in normal and pathological conditions. Abst…

P1605Increased irregularity and spectral complexity of the intrinsic pacemaker beat-to-beat variability correlates with increased metabolic syndrome components

Abstract Background Metabolic syndrome (MetS) is becoming one of the future potential leading risk factors for heart and cardiovascular disease. MetS relates to a condition associated with at least three metabolic risk factors raising risk for health diseases concomitantly such as diabetes, stroke, hypertension, obesity and dyslipidemia. This can lead to chest pain, heart attack, heart damage and overall higher prevalence of cardiovascular disease, atrial fibrillation and sudden cardiac death. One of the underlying mechanisms of the progressive remodeling in presence of MetS components could be altered automaticity, which would reflect modifications of sinus node activity. These phenomena c…

Epicardial-limited electrophysiological heterogeneities do not facilitate ventricular arrhythmia induction. An experimental study

The electrophysiological heterogeneities of the myocardium are associated with vulnerability to arrhythmias. This study presents an experimental heterogeneity model based on local epicardial cooling/warming.

Efficacy of a proprioceptive exercise program in patients with nonspecific neck pain: a randomized controlled trial.

BACKGROUND Nonspecific neck pain is associated with chronic pain, disability, reduced cervical mobility, postural control disorders and impaired proprioceptive control. AIM The aim of this study was to compare the effectiveness of two therapeutic exercise programs (i.e. cervical proprioception and cervical mobility) in reducing pain and disability in individuals with nonspecific neck pain. We further aimed to compare the effectiveness of the two treatments in improving pressure pain threshold, cervical range of motion and head repositioning accuracy. DESIGN This study was designed as a randomized controlled trial. SETTING This study took place in a private rehabilitation clinic. POPULATION …

P315Study of the induction and characteristics of ventricular fibrillation in an experimental model of metabolic syndrome

QT interval heterogeneities induced through local epicardial warming/cooling. An experimental study

[EN] ntroduction and objectives Abnormal QT interval durations and dispersions have been associated with increased risk of ventricular arrhythmias. The present study examines the possible arrhythmogenic effect of inducing QT interval variations through local epicardial cooling and warming. Methods In 10 isolated rabbit hearts, the temperatures of epicardial regions of the left ventricle were modified in a stepwise manner (from 22 °C to 42 °C) with simultaneous electrogram recording in these regions and in others of the same ventricle. QT and activation-recovery intervals were determined during sinus rhythm, whereas conduction velocity and ventricular arrhythmia induction were determined dur…