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

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…

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…

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…

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…

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…

Pentoxifylline in liver ischemia and reperfusion.

Pentoxifylline is a methylxanthine compound which was first filed in 1973 and registered in 1974 in the United States by Sanofi-Aventis Deustchland Gmbh for the treatment of intermittent claudication for chronic occlusive arterial disease. This methylxanthine was later discovered to be a phosphodiesterase inhibitor. Furthermore, its hemorheological properties and its function as an inhibitor of inflammatory cytokines, like TNF- α, allowed researchers to study its effects in organ ischemia and reperfusion and transplantation. Although this drug has demonstrated beneficial effects, the mechanisms by which Pentoxifylline exerts a protective effect are not fully understood. This paper focuses o…