Germán Parra

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

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 ventricular fibrillation assessed by mapping techniques was related to the dominant frequency, normalized spectral energy, signal regularity index, and their corresponding coefficients of variation, as well as the area of the regions of interest identified on the basis of these parameters. In the multivariate analysis, we used as independent variables the area of the regions of interest related to the spectral energy and the coefficient of variation of the energy (complexity index=-0.005×area of the spectral energy regions -2.234×coefficient of variation of the energy+1.578; P=.0001; r=0.68). CONCLUSIONS The spectral and morphological indicators and, independently, those derived from the analysis of normalized energy regions of interest provide a reliable approach to the evaluation of the complexity of ventricular fibrillation as an alternative to complex mapping techniques.

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 evaluate the different components of MetS: morphological and blood pressure measurements, glucose tolerance determination, and the analysis of several plasma markers. At the end of the experimental period, animals developed central obesity, mild hypertension, pre-diabetes, and dyslipidemia with low HDL, high LDL, and an increase of triglyceride (TG) levels, thus reproducing the main components of human MetS. This chronic model allows new perspectives for understanding the underlying mechanisms in the progression of the disease, the detection of preclinical and clinical markers that allow the identification of patients at risk, or even the testing of new therapeutic approaches for the treatment of this complex pathology.

Effects of JTV-519 on stretch-induced manifestations of mechanoelectric feedback

JTV‐519 is a 1,4‐benzothiazepine derivative with multichannel effects that inhibits Ca2+ release from the sarcoplasmic reticulum and stabilizes the closed state of the ryanodine receptor, preventing myocardial damage and the induction of arrhythmias during Ca2+ overload. Mechanical stretch increases cellular Na+ inflow, activates the reverse mode of the Na+/Ca2+ exchanger, and modifies Ca2+ handling and myocardial electrophysiology, favoring arrhythmogenesis. This study aims to determine whether JTV‐519 modifies the stretch‐induced manifestations of mechanoelectric feedback. The ventricular fibrillation (VF) modifications induced by acute stretch were studied in Langendorff‐perfused rabbit hearts using epicardial multiple electrodes under control conditions (n=9) or during JTV‐519 perfusion: 0.1 μmol/L (n=9) and 1 μmol/L (n=9). Spectral and mapping techniques were used to establish the baseline, stretch and post‐stretch VF characteristics. JTV‐519 slowed baseline VF and decreased activation complexity. These effects were dose‐dependent (baseline VF dominant frequency: control=13.9±2.2 Hz; JTV 0.1 μmol/L=11.1±1.1 Hz, P<.01; JTV 1 μmol/L=6.6±1.1 Hz, P<.0001). The stretch‐induced acceleration of VF (control=38.8%) was significantly reduced by JTV‐519 0.1 μmol/L (19.8%) and abolished by JTV 1 μmol/L (−1.5%). During stretch, the VF activation complexity index was reduced in both JTV‐519 series (control=1.60±0.15; JTV 0.1 μmol/L=1.13±0.3, P<.0001; JTV 1 μmol/L=0.57±0.21, P<.0001), and was independently related to VF dominant frequency (R=.82; P<.0001). The fifth percentile of the VF activation intervals, conduction velocity and wavelength entered the multiple linear regression model using dominant frequency as the dependent variable (R=−.84; P<.0001). In conclusion, JTV‐519 slowed and simplified the baseline VF activation patterns and abolished the stretch‐induced manifestations of mechanoelectric feedback.