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…

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…

«LA FISIOLOGÍA INVISIBLE»: recursos audiovisuales para la enseñanza de la fisiología en ciencias de la salud

[EN] Human physiology is a basic subject during the first courses related to health sciences. Physiology as a discipline is markedly heterogeneous, since it includes anatomical, functional, molecular and biochemical notions, all widely interconnected. For this reason, it is difficult for students to integrate this knowledge, especially in the first years where the rest of related subjects (general biology, biochemistry, etc.) are taken at the same time. To facilitate this learning, the audio-visual material implies a great support when it comes to specifying abstract concepts and data obtained through complex experiments. Currently students are digital natives, and find the audiovisual tool…

Comparison of Intensity-based B-splines and Point-to-Pixel Tracking Techniques for Motion Reduction in Optical Mapping

Suppression of motion artifacts (MA) in cardiac optical mapping usually requires uncoupling of cardiac contraction by restriction techniques, which are known to have important effects on cardiac physiology deteriorating the quality of acquisitions and their interpretation. In this study, we propose to assess the performance of two independent intensity-based post-processing strategies to minimize MAs during registration. A point-to-pixel block-matching classical similarity-based tracking with displacement interpolation is compared to a well-known non-rigid registration algorithm where the deformation field is obtained using cubic splines. Both strategies were tested on synthetic and real op…

Cardiac electrical defects in progeroid mice and Hutchinson-Gilford progeria syndrome patients with nuclear lamina alterations

This work was supported by Spanish Ministry of Economy and Competitiveness (MINECO) Grants SAF2010-16044 and SAF2013-46663-R (to V.A.), SAF2011-30312 and SAF2014-58286-C2-1-R (to L.H.-M.), SAF2011-30088 (to E.D.), and SAF2014-52413-R (to C.L.-O.) and Fondo de Investigación Sanitaria del Instituto de Salud Carlos III Grants RD12/0042/0028 (to V.A.), RD12/0042/0011 (to J.T.), and RD12/0042/0002 (to L.H.-M.), with cofunding from the Fondo Europeo de Desarrollo Regional and the Progeria Research Foundation. J.A.G. is the recipient of a U-Mobility Grant from the Marie Curie cofunding of Regional, National and International Programme (Grant 246550). The Instituto Universitario de Oncología is sup…

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

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 …

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…

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…

Low-Cost Optical Mapping Systems for Panoramic Imaging of Complex Arrhythmias and Drug-Action in Translational Heart Models.

[EN] Panoramic optical mapping is the primary method for imaging electrophysiological activity from the entire outer surface of Langendorff-perfused hearts. To date, it is the only method of simultaneously measuring multiple key electrophysiological parameters, such as transmembrane voltage and intracellular free calcium, at high spatial and temporal resolution. Despite the impact it has already had on the fields of cardiac arrhythmias and whole-heart computational modeling, present-day system designs precludes its adoption by the broader cardiovascular research community because of their high costs. Taking advantage of recent technological advances, we developed and validated low-cost opti…

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…

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.

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