Luis Such-Miquel

Pharmacological modifications of the stretch-induced effects on ventricular fibrillation in perfused rabbit hearts

Stretch induces modifications in myocardial electrical and mechanical activity. Besides the effects of substances that block the stretch-activated channels, other substances could modulate the effects of stretch through different mechanisms that affect Ca(2+) handling by myocytes. Thirty-six Langendorff-perfused rabbit hearts were used to analyze the effects of the Na(+)/Ca(2+) exchanger blocker KB-R7943, propranolol, and the adenosine A(2) receptor antagonist SCH-58261 on the acceleration of ventricular fibrillation (VF) produced by acute myocardial stretching. VF recordings were obtained with two epicardial multiple electrodes before, during, and after local stretching in four experimental series: control (n = 9), KB-R7943 (1 microM, n = 9), propranolol (1 microM, n = 9), and SCH-58261 (1 microM, n = 9). Both the Na(+)/Ca(2+) exchanger blocker KB-R7943 and propranolol induced a significant reduction (P < 0.001 and P < 0.05, respectively) in the dominant frequency increments produced by stretching with respect to the control and SCH-58261 series (control = 49.9%, SCH-58261 = 52.1%, KB-R7943 = 9.5%, and propranolol = 12.5%). The median of the activation intervals, the functional refractory period, and the wavelength of the activation process during VF decreased significantly under stretch in the control and SCH-58261 series, whereas no significant variations were observed in the propranolol and KB-R7943 series, with the exception of a slight but significant decrease in the median of the fibrillation intervals in the KB-R7943 series. KB-R7943 and propranolol induced a significant reduction in the activation maps complexity increment produced by stretch with respect to the control and SCH-58261 series. In conclusion, the electrophysiological effects responsible for stretch-induced VF acceleration in the rabbit heart are reduced by the Na(+)/Ca(2+) exchanger blocker KB-R7943 and by propranolol but not by the adenosine A(2) receptor antagonist SCH-58261.

Análisis tiempo-frecuencia de la fibrilación ventricular. Estudio experimental

INTRODUCTION AND OBJECTIVES The analysis of frequency variability during ventricular fibrillation has yielded inconsistent results. We used an experimental model of ventricular fibrillation, with a short timescale, to analyze variations in frequency and their associated spatial distribution. METHODS Epicardial recordings of ventricular fibrillation were made in 10 perfused isolated rabbit heart preparations using a multiple electrode system (i.e., 240 unipolar electrodes). Both spectral and time-frequency analysis were used to derive the dominant frequency in the anterolateral wall of the left ventricle. RESULTS Linear regression analysis showed that there was a good correlation between the dominant frequency obtained using the two signal analysis methods: frequency (spectral analysis) = 1.01 x frequency (time-frequency analysis) -- 0.4 (r=0.9; P< .0001; standard error of the estimate, 2.2 Hz). In all cases except one, the dominant frequency exhibited a significant temporal variation on a short timescale (time-frequency analysis); the coefficient of variation was between 0.19 (0.06) and 0.24 (0.07) (NS). In all cases, there were significant differences between regions. The location at which the frequency was highest varied according to the timepoint considered, though it was predominantly in the apical or anterior zone. CONCLUSIONS In the absence of external modulating factors, the frequency of ventricular fibrillation exhibits temporal and spatial variations which can be observed at short timescales. In the free wall of the left ventricle, the dominant frequency is highest in the apical and anterior zones, and the maximum frequencies are most often found in these zones.Introduccion y objetivos El analisis de la variabilidad de la frecuencia durante la fibrilacion ventricular ha aportado resultados no uniformes. En un modelo experimental de fibrilacion ventricular se analiza, en una escala temporal reducida, las variaciones de la frecuencia y su distribucion espacial. Metodos En 10 preparaciones de corazon aislado y perfundido de conejo, se efectuan registros epicardicos de la fibrilacion ventricular con un electrodo multiple (240 electrodos unipolares) y se aplican metodos de analisis espectrales y de tiempo-frecuencia para obtener la frecuencia dominante en la pared anterolateral del ventriculo izquierdo. Resultados La recta de regresion obtenida al relacionar los valores de la frecuencia dominante obtenidos con los 2 metodos de analisis muestra una buena correlacion entre ambos: frecuencia (metodo espectral) = 1,01 × frecuencia (metodo tiempo-frecuencia) – 0,4 (r = 0,9; p Conclusiones En ausencia de factores moduladores externos, la fibrilacion ventricular presenta variaciones temporales y espaciales de la frecuencia que se objetivan en escalas de tiempo reducidas. En la pared libre del ventriculo izquierdo, la frecuencia dominante es mayor en las zonas apicales y anteriores, zonas en las que se ubican con mayor frecuencia los valores maximos.

Modifications of mechanoelectric feedback induced by 2,3-butanedione monoxime and Blebbistatin in Langendorff-perfused rabbit hearts.

Myocardial stretching is an arrhythmogenic factor. Optical techniques and mechanical uncouplers are used to study the mechanoelectric feedback. The aim of this study is to determine whether the mechanical uncouplers 2,3‐butanedione monoxime and Blebbistatin hinder or modify the electrophysiological effects of acute mechanical stretch.

Effects of chronic exercise on myocardial refractoriness : a study on isolated rabbit heart

Aim:  To determine whether chronic physical training increases atrial and ventricular refractoriness in isolated rabbit heart.

Selective Myocardial Isolation and Ventricular Fibrillation

Background: Few experimental studies have analyzed the effects of selective radiofrequency (RF) lesions upon ventricular fibrillation (VF). The RF‐induced isolation of selected zones would make it possible to determine whether these zones are essential for existence of the arrhythmia.

Analyzing the electrophysiological effects of local epicardial temperature in experimental studies with isolated hearts.

As a result of their modulating effects upon myocardial electrophysiology, both hypo- and hyperthermia can be used to study the mechanisms that generate or sustain cardiac arrhythmias. The present study describes an original electrode developed with thick-film technology and capable of controlling regional temperature variations in the epicardium while simultaneously registering its electrical activity. In this way, it is possible to measure electrophysiological parameters of the heart at different temperatures. The results obtained with this device in a study with isolated and perfused rabbit hearts are reported. An exploration has been made of the effects of local temperature changes upon the electrophysiological parameters implicated in myocardial conduction. Likewise, an analysis has been made of the influence of local temperature upon ventricular fibrillation activation frequency. It is concluded that both regional hypo- and hyperthermia exert reversible and opposite effects upon myocardial refractoriness and conduction velocity in the altered zone. The ventricular activation wavelength determined during constant pacing at 250 ms cycles is not significantly modified, however. During ventricular fibrillation, the changes in the fibrillatory frequency do not seem to be transmitted to normal temperature zones.

Ventricular fibrillation conduction through an isthmus of preserved myocardium between radiofrequency lesions.

Selective local acceleration of myocardial activation during ventricular fibrillation (VF) contributes information on the interactions between neighboring zones during the arrhythmia. This study analyzes these interactions, centering the observations on an isthmus of myocardium between two radiofrequency (RF) lesions.

New epicardial mapping electrode with warming/cooling function for experimental electrophysiology studies.

Cardiac electrical activity is influenced by temperature. In experimental models, the induction of hypothermia and/or hyperthermia has been used for the study of mechanisms of cardiac arrhythmia. A system that allows for localized, controlled induction, besides simultaneously recording electrical activity in the same induced area, needs to be developed ad hoc. This article describes the construction and application of a new system capable of locally modifying the epicardial temperature of isolated hearts and of carrying out cardiac mapping with sufficient spatial resolution. The system is based on a thermoelectric refrigerator and an array of 128 stainless steel unipolar electrodes in encapsulated epoxy of good thermal conductivity. The surface of the electrode is shaped to match the ventricular curvature. The electrode-device was tested on 7 isolated perfused rabbit hearts following the Langendorff technique. Quality recordings were obtained for the left ventricle at temperatures of 37° C, 22° C and 42° C. The effects of temperature were explored in relation to two electrophysiological parameters: the QT interval during sinus rhythm and the VV interval during ventricular fibrillation. The results indicate that this is a suitable method for creating and analyzing electrophysiological heterogeneities induced by temperature in the experimental model.

Influencia del tipo de registro (unipolar o bipolar) en las características espectrales de los registros epicárdicos de la fibrilación ventricular. Estudio experimental

Introduction and objectives. The aim of this study was to examine the hypothesis that the recording mode (ie, unipolar or bipolar) affects the information obtained using spectral analysis techniques during ventricular fibrillation by carrying out an experiment using epicardial electrodes. Methods. Recordings of ventricular fibrillation were obtained in 29 isolated rabbit hearts using a multipleelectrode probe located on the left ventricular free wall. The parameter values obtained in the frequency domain (by Fourier analysis) using unipolar or bipolar electrodes, different interelectrode distances, and different orientations (ie, horizontal, vertical, or diagonal) were compared. Results. Changing the recording mode (ie, unipolar to bipolar) or the interelectrode distance significantly altered the mean frequency (P<.0001) and the normalized energy of the spectrum (±1 Hz) around the dominant frequency (P<.05), though the changes were small relative to the dominant frequency. Cross-spectral analysis showed that the coherence between unipolar recordings decreased as the interelectrode distance increased, while the opposite occurred with the coherence between unipolar and bipolar recordings. The 2 coherences were inversely correlated such that the greater the former coherence, the less the coherence between unipolar and bipolar recordings (r=0.29; P<.0001; n=348). Conclusions. The recording mode (ie, unipolar or bipolar) used influenced the information obtained using spectral analysis techniques from epicardial recordings of

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 28 weeks with high-fat, high-sucrose diet. We measured weight, morphological characteristics, blood pressure, glycaemia, standard plasma biochemistry and the metabolomic profile at weeks 14 and 28. Liver histological changes were evaluated using hematoxylin-eosin staining. A mixed model ANOVA or unpaired t-test were used for statistical analysis (P<0.05). Weight, abdominal contour, body mass index, systolic, diastolic and mean arterial pressure increased in the MetS group at weeks 14 and 28. Glucose, triglycerides, LDL, GOT-AST, GOT/GPT, bilirubin and bile acid increased, whereas HDL decreased in the MetS group at weeks 14 and 28. We found a 40% increase in hepatocyte area and lipid vacuoles infiltration in the liver from MetS rabbits. Metabolomic analysis revealed differences in metabolites related to fatty acids, energetic metabolism and microbiota, compounds linked with cardiovascular disease. Administration of high-fat and high-sucrose diet during 28 weeks induced obesity, glucose intolerance, hypertension, non-alcoholic hepatic steatosis and metabolic alterations, thus reproducing the main clinical manifestations of the metabolic syndrome in humans. This experimental model should provide a valuable tool for studies into the mechanisms of cardiovascular problems related to MetS, with special relevance in the study of cardiovascular remodeling, arrhythmias and SCD.