El suero de seno coronario tras un infarto de miocardio induce angiogénesis y reparación de la obstrucción microvascular. Implicación del factor inducible por hipoxia-1A / Coronary serum obtained after myocardial infarction induces angiogenesis and microvascular obstruction repair. Role of hypoxia-inducible factor-1A

Introducción y objetivos: El objetivo es estudiar la angiogénesis coronaria inducida por el suero coronario y la implicación del factor inducible por hipoxia-1A (FIH-1A) en la reparación de la obstrucción microvascular (OMV) tras un infarto agudo de miocardio (IAM). Métodos: Se indujo un IAM en cerdos mediante oclusión coronaria durante 90 min. Se dividió a los animales entre 1 grupo de control y 4 grupos con IAM: sin reperfusión y 1 min, 1 semana y 1 mes tras la reperfusión. Se cuantificaron la OMV y la densidad microvascular. Se determinó la capacidad angiogénica del suero coronario mediante una prueba de tubulogénesis in vitro. Se determinaron las concentraciones circulantes del FIH-1A, su implicación en el miocardio infartado y el efecto del bloqueo del FIH-1A in vitro. Resultados: En la zona infartada, la microvascularización disminuye tras 90 min de isquemia, la OMV aparece tras 1 min de reperfusión, es máxima 1 semana tras la reperfusión y se resuelve en 1 mes. La capacidad angiogénica del suero aumenta durante la isquemia y 1 min tras la reperfusión (32 ± 4 y 41 ± 9 frente a 3 ± 3 tubos en el grupo de control; p < 0,01). Las concentraciones circulantes del FIH-1A se incrementan durante la isquemia (5 min de isquemia: 273 ± 52 frente a 148 ± 48 pg/ml de los controles; p < 0,01) y se hallan en la microvasculatura de todos los grupos con IAM (sin reperfusión frente a control, el 67 ± 5% frente al 15 ± 17%; p < 0,01). El bloqueo del FIH-1A in vitro reduce la capacidad angiogénica inducida por el suero. Conclusiones: El suero coronario activa la neoangiogénesis desde antes de la reperfusión, y el FIH-1A podría tener un papel crucial. La capacidad angiogénica del suero coronario puede contribuir a la comprensión de la fisiopatología tras el IAM

Introduction and objectives: Microvascular obstruction (MVO) exerts deleterious effects following acute myocardial infarction (AMI). We investigated coronary angiogenesis induced by coronary serum and the role of hypoxia-inducible factor-1A (HIF-1A) in MVO repair. Methods: Myocardial infarction was induced in swine by transitory 90-minute coronary occlusion. The pigs were divided into a control group and 4 AMI groups: no reperfusion, 1 minute, 1 week and 1 month after reperfusion. Microvascular obstruction and microvessel density were quantified. The proangiogenic effect of coronary serum drawn from coronary sinus on endothelial cells was evaluated using an in vitro tubulogenesis assay. Circulating and myocardial HIF-1A levels and the effect of in vitro blockade of HIF-1A was assessed. Results: Compared with control myocardium, microvessel density decreased at 90-minute ischemia, and MVO first occurred at 1 minute after reperfusion. Both peaked at 1 week and almost completely resolved at 1 month. Coronary serum exerted a neoangiogenic effect on coronary endothelial cells in vitro, peaking at ischemia and 1 minute postreperfusion (32 ± 4 and 41 ± 9 tubes vs control: 3 ± 3 tubes; P < .01). Hypoxia-inducible factor-1A increased in serum during ischemia (5-minute ischemia: 273 ± 52 pg/mL vs control: 148 ± 48 pg/mL; P < .01) being present on microvessels of all AMI groups (no reperfusion: 67% ± 5% vs control: 15% ± 17%; P < .01). In vitro blockade of HIF-1A reduced the angiogenic response induced by serum. Conclusions: Coronary serum represents a potent neoangiogenic stimulus even before reperfusion; HIF-1A might be crucial. Coronary neoangiogenesis induced by coronary serum can contribute to understanding the pathophysiology of AMI

Coronary Serum Obtained After Myocardial Infarction Induces Angiogenesis and Microvascular Obstruction Repair. Role of Hypoxia-inducible Factor-1A.

INTRODUCTION AND OBJECTIVES: Microvascular obstruction (MVO) exerts deleterious effects following acute myocardial infarction (AMI). We investigated coronary angiogenesis induced by coronary serum and the role of hypoxia-inducible factor-1A (HIF-1A) in MVO repair. METHODS: Myocardial infarction was induced in swine by transitory 90-minute coronary occlusion. The pigs were divided into a control group and 4 AMI groups: no reperfusion, 1minute, 1 week and 1 month after reperfusion. Microvascular obstruction and microvessel density were quantified. The proangiogenic effect of coronary serum drawn from coronary sinus on endothelial cells was evaluated using an in vitro tubulogenesis assay. Circulating and myocardial HIF-1A levels and the effect of in vitro blockade of HIF-1A was assessed. RESULTS: Compared with control myocardium, microvessel density decreased at 90-minute ischemia, and MVO first occurred at 1minute after reperfusion. Both peaked at 1 week and almost completely resolved at 1 month. Coronary serum exerted a neoangiogenic effect on coronary endothelial cells in vitro, peaking at ischemia and 1minute postreperfusion (32 ± 4 and 41 ± 9 tubes vs control: 3 ± 3 tubes; P < .01). Hypoxia-inducible factor-1A increased in serum during ischemia (5-minute ischemia: 273 ± 52 pg/mL vs control: 148 ± 48 pg/mL; P < .01) being present on microvessels of all AMI groups (no reperfusion: 67% ± 5% vs control: 15% ± 17%; P < .01). In vitro blockade of HIF-1A reduced the angiogenic response induced by serum. CONCLUSIONS: Coronary serum represents a potent neoangiogenic stimulus even before reperfusion; HIF-1A might be crucial. Coronary neoangiogenesis induced by coronary serum can contribute to understanding the pathophysiology of AMI.

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

BACKGROUND: 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. METHODS: In nine isolated rabbit hearts, a gap of preserved myocardium was established between two RF lesions in the anterolateral left ventricle (LV) wall. Before, during, and after increasing the spatial heterogeneity of VF by local myocardial stretching, VF epicardial recordings were obtained. RESULTS: Local stretch in the anterior LV wall decreased the excitable window (17 ± 7 ms vs 26 ± 7 ms; P < 0.05) and increased the dominant frequency (DFr; 18.9 ± 5.0 Hz vs 15.2 ± 3.6 Hz; P < 0.05) in this zone, without changes in the non-stretched posterolateral zone (25 ± 4 ms vs 27 ± 6 ms, ns and 14.1 ± 2.7 Hz vs 14.3 ± 3.0 Hz, ns). The DFr ratio at both sides of the gap was inversely correlated to the excitable window ratio (R = -0.57; P = 0.002). Before (31% vs 26%), during (29% vs 22%), and after stretch suppression (35% vs 25%), the wavefronts passing through the gap from the posterolateral to the anterior LV wall were seen to predominate. The number of wavefronts that passed from the anterior to the posterolateral LV wall was related to the excitable window in this zone (R = 0.41; P = 0.03). CONCLUSIONS: The VF acceleration induced in the stretched zone does not increase the flow of wavefronts toward the non-stretched zone in the adjacent gap of preserved myocardium. The absence of significant changes in the electrophysiological parameters of the non-stretched myocardium limits the arrival of wavefronts in this zone.

Modificaciones de la fibrilación ventricular y de la capacidad de captura inducidas por una lesión lineal con radiofrecuencia / Modifications in ventricular fibrillation and capture capacity induced by a linear radiofrequency lesion

Introducción y objetivos. Analizar los efectos, en la fibrilación ventricular y en la capacidad de capturar al miocardio mediante estimulación a frecuencias rápidas, de una lesión lineal producida con radiofrecuencia. Métodos. En 22 corazones de conejo aislados y perfundidos, se utilizaron electrodos múltiples epicárdicos para registrar la fibrilación ventricular. Se analizaron los mapas de activación al aplicar trenes de estímulos a tres frecuencias distintas, cercanas a las de la arritmia, en tres situaciones: a) basalmente; b) tras producir con radiofrecuencia una lesión en la pared libre del ventrículo izquierdo (longitud, 10±1mm), y c) tras ampliar su extensión (longitud, 23±2mm). Resultados. Tras la lesión, se observó una disminución de la regularidad de las señales registradas y variaciones significativas en la dirección de los frentes de activación. Con la lesión ampliada, se incrementaron ligeramente los episodios con al menos tres capturas consecutivas al estimular con ciclos un 10% más largos que los de la arritmia (basal, 0,6±0,7; lesión inicial, 1±1, diferencias no significativas; lesión ampliada, 3±2,8; p<0,001), mientras que se redujeron los obtenidos al estimular con ciclos un 10% más cortos que los de la arritmia. Conclusiones. La lesión efectuada con radiofrecuencia aumenta la heterogeneidad de la activación miocárdica durante la fibrilación ventricular y modifica la llegada de los frentes de activación a las zonas adyacentes. La estimulación durante la fibrilación ventricular a frecuencias rápidas provoca capturas ocasionales durante al menos tres estímulos consecutivos. La lesión ampliada incrementa ligeramente la capacidad de captura al utilizar ciclos ligeramente más largos que los de la fibrilación ventricular (AU)

Introduction and objectives. An analysis was made of the effects of a radiofrequency-induced linear lesion during ventricular fibrillation and the capacity to capture myocardium through high-frequency pacing. Methods. Using multiple epicardial electrodes, ventricular fibrillation was recorded in 22 isolated perfused rabbit hearts, analyzing the activation maps upon applying trains of stimuli at 3 different frequencies close to that of the arrhythmia: a) at baseline; b) after radio-frequency ablation to induce a lesion of the left ventricular free wall (length=10 [1]mm), and c) after lengthening the lesion (length=23 [2]mm). Results. Following lesion induction, the regularity of the recorded signals decreased and significant variations in the direction of the activation fronts were observed. On lengthening the lesion, there was a slight increase in the episodes with at least 3 consecutive captures when pacing at cycles 10% longer than the arrhythmia (baseline: 0.6 [0.7]; initial lesion: 1 [1] no significant differences; lengthened lesion: 3 [2.8]; P<.001), while a decrease was observed in those obtained upon pacing at cycles 10% shorter than the arrhythmia. Conclusions. The radio-frequency -induced lesion increases the heterogeneity of myocardial activation during ventricular fibrillation and modifies arrival of the activation fronts in the adjacent zones. High-frequency pacing during ventricular fibrillation produces occasional captures during at least 3 consecutive stimuli. The lengthened lesion in turn slightly increases capture capacity when using cycles slightly longer than the arrhythmia (AU)

Modifications in ventricular fibrillation and capture capacity induced by a linear radiofrequency lesion.

INTRODUCTION AND OBJECTIVES: An analysis was made of the effects of a radiofrequency-induced linear lesion during ventricular fibrillation and the capacity to capture myocardium through high-frequency pacing. METHODS: Using multiple epicardial electrodes, ventricular fibrillation was recorded in 22 isolated perfused rabbit hearts, analyzing the activation maps upon applying trains of stimuli at 3 different frequencies close to that of the arrhythmia: a) at baseline; b) after radio-frequency ablation to induce a lesion of the left ventricular free wall (length=10 [1] mm), and c) after lengthening the lesion (length=23 [2] mm). RESULTS: Following lesion induction, the regularity of the recorded signals decreased and significant variations in the direction of the activation fronts were observed. On lengthening the lesion, there was a slight increase in the episodes with at least 3 consecutive captures when pacing at cycles 10% longer than the arrhythmia (baseline: 0.6 [0.7]; initial lesion: 1 [1], no significant differences; lengthened lesion: 3 [2.8]; P<.001), while a decrease was observed in those obtained upon pacing at cycles 10% shorter than the arrhythmia. CONCLUSIONS: The radio-frequency -induced lesion increases the heterogeneity of myocardial activation during ventricular fibrillation and modifies arrival of the activation fronts in the adjacent zones. High-frequency pacing during ventricular fibrillation produces occasional captures during at least 3 consecutive stimuli. The lengthened lesion in turn slightly increases capture capacity when using cycles slightly longer than the arrhythmia.

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.

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.

[Changes in the spectral characteristics of ventricular fibrillation in lesions produced by radiofrequency ablation. An experimental study]. / Modificaciones de las características espectrales de la fibrilación ventricular en las lesiones producidas con radiofrecuencia. Estudio experimental.

INTRODUCTION AND OBJECTIVES: Although electro- physiological databases contain information about changes in the time domain in lesions produced by radiofrequency ablation, very few data on changes in the frequency domain are available. The aim of this study was to investigate changes in the spectral characteristics of ventricular fibrillation in zones with radiofrequency lesions. METHODS: Recordings of ventricular fibrillation were obtained in 11 isolated perfused rabbit heart preparations using a multiple epicardial electrode located on the left ventricular free wall. Spectral parameters derived by Fourier analysis before and after the creation of transmural radiofrequency lesions were compared. RESULTS: In the ablated zones, significant reductions were observed in the spectral density of the dominant (0.168+/-0.113 mV(2)/Hz vs 0.025+/-0.018 mV(2)/Hz; P< .001) and mean frequencies (0.053+/-0.057 mV(2)/Hz vs 0.012+/-0.016 mV(2)/Hz; P< .001), the normalized energy around the dominant frequency (0.860+/-0.570 vs 0.128+/-0.091; P< .001), and the standard deviation of the power spectrum (0.031+/-0.020 mV(2)/Hz vs 0.004+/-0.001 mV(2)/Hz; P< .001). There was no significant change in the dominant (16.2+/-5.6 vs 14.8+/-1.8 Hz) or mean frequency (17.7+/-3.4 vs 16.6+/-1.3 Hz). The spectral parameters that could be used in a multivariate model to identify the lesion were the standard deviation of the power spectrum and the spectral density of the mean frequency. CONCLUSIONS: During ventricular fibrillation, the spectral parameters associated with spectral power and spectral energy were significantly altered in zones with radiofrequency lesions and could be used to identify those zones. There was no significant change in either the dominant or mean frequency in these zones.

Modificaciones de las características espectrales de la fibrilación ventricular en las lesiones producidas con radiofrecuencia. Estudio experimental / Changes in the spectral characteristics of ventricular fibrillation in lesions produced by radiofrequency ablation. An experimental study

Introducción y objetivos. Aunque se dispone de información sobre las modificaciones en el dominio del tiempo de los registros electrofisiológicos en zonas lesionadas con radiofrecuencia, los datos disponibles en el dominio de la frecuencia son muy escasos. Se analizan las modificaciones de las características espectrales de la fibrilación ventricular en zonas lesionadas con radiofrecuencia. Métodos. En 11 preparaciones de corazón aislado y perfundido de conejo, se registra la fibrilación ventricular con un electrodo múltiple epicárdico situado en la pared libre ventricular izquierda. Se comparan los parámetros espectrales obtenidos mediante análisis de Fourier antes y después de practicar lesiones transmurales con radiofrecuencia. Resultados. En las zonas lesionadas disminuye significativamente la densidad espectral de las frecuencias dominante (0,168 ± 0,113 y 0,025 ± 0,018 mV2/Hz; p < 0,001) y media (0,053 ± 0,057 y 0,012 ± 0,016 mV2/Hz; p < 0,001), la energía normalizada alrededor de la frecuencia dominante (0,860 ± 0,570 y 0,128 ± 0,091; p < 0,001) y la desviación típica del espectro de potencias (0,031 ± 0,020 y 0,004 ± 0,001 mV2/Hz; p < 0,001). No se modifican significativamente las frecuencias dominante (16,2 ± 5,6 y 14,8 ± 1,8 Hz) y media (17,7 ± 3,4 y 16,6 ± 1,3 Hz). Los parámetros espectrales aceptados en el modelo multivariable para indicar que los registros se efectúan en la lesión son la desviación típica del espectro de potencias y la densidad espectral de la frecuencia media. Conclusiones. Durante la fibrilación ventricular, los parámetros relacionados con la potencia y la energía espectral muestran modificaciones significativas en las zonas lesionadas con radiofrecuencia y pueden ayudar a identificarlas. Las frecuencias dominante y media no se modifican significativamente en las zonas lesionadas

Introduction and objectives. Although electro- physiological databases contain information about changes in the time domain in lesions produced by radiofrequency ablation, very few data on changes in the frequency domain are available. The aim of this study was to investigate changes in the spectral characteristics of ventricular fibrillation in zones with radiofrequency lesions. Methods. Recordings of ventricular fibrillation were obtained in 11 isolated perfused rabbit heart preparations using a multiple epicardial electrode located on the left ventricular free wall. Spectral parameters derived by Fourier analysis before and after the creation of transmural radiofrequency lesions were compared. Results. In the ablated zones, significant reductions were observed in the spectral density of the dominant (0.168±0.113 mV2/Hz vs 0.025±0.018 mV2/Hz; P<.001) and mean frequencies (0.053±0.057 mV2/Hz vs 0.012±0.016 mV2/Hz; P<.001), the normalized energy around the dominant frequency (0.860±0.570 vs 0.128±0.091; P<.001), and the standard deviation of the power spectrum (0.031±0.020 mV2/Hz vs 0.004±0.001 mV2/Hz; P<.001). There was no significant change in the dominant (16.2±5.6 vs 14.8±1.8 Hz) or mean frequency (17.7±3.4 vs 16.6±1.3 Hz). The spectral parameters that could be used in a multivariate model to identify the lesion were the standard deviation of the power spectrum and the spectral density of the mean frequency. Conclusions. During ventricular fibrillation, the spectral parameters associated with spectral power and spectral energy were significantly altered in zones with radiofrequency lesions and could be used to identify those zones. There was no significant change in either the dominant or mean frequency in these zones

[Effect of streptomycin on stretch-induced change in myocardial activation during ventricular fibrillation]. / Efectos de la estreptomicina en las modificaciones de la activación miocárdica durante la fibrilación ventricular inducidas por el estiramiento.

The aim of this study was to determine whether the changes in myocardial activation pattern resulting from acute stretching during ventricular fibrillation can be counteracted by administering a compound that blocks receptors sensitive to stretch. The study involved 16 isolated rabbit hearts, in which refractoriness and activation frequency during ventricular fibrillation were measured before, during and after localized acute stretching of the left ventricular free wall, either without (series A, n=8) or with (series B, n=8) the presence of streptomycin, 200 micromol. At baseline and during and after stretching, ventricular fibrillation was slower with streptomycin perfusion in series B than in series A (dominant frequency at baseline, 13+/-2 Hz vs. 16+/-2 Hz, respectively; P< .005; dominant frequency with stretching, 14+/-2 Hz vs. 19+/-3 Hz, respectively; P< .005). Streptomycin attenuated the electrophysiological changes produced by stretching and had a direct effect on refractoriness and activation frequency during ventricular fibrillation.

[Influence of recording mode (unipolar or bipolar) on the spectral characteristics of epicardial recordings in ventricular fibrillation. An experimental study]. / 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 (i.e., 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 multiple-electrode 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 (i.e., horizontal, vertical or diagonal) were compared. RESULTS: Changing the recording mode (i.e., 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 two 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 (i.e., unipolar or bipolar) used influenced the information obtained using spectral analysis techniques from epicardial recordings of ventricular fibrillation. Differences were observed in the mean frequency and in the frequency distribution, but they were very small relative to the dominant frequency.

Influencia del tipo de registro (unipolar o bipolar) en las características espectrales de los registros epicárdicos de la fibrilación ventricular. Estudio experimental / Influence of recording mode (unipolar or bipolar) on the spectral characteristics of epicardial recordings in ventricular fibrillation. An experimental study

Introducción y objetivos. Se evalúa la hipótesis de que el tipo de registro (unipolar o bipolar) influye en la información obtenida mediante técnicas espectrales durante la fibrilación ventricular en un modelo experimental que utiliza electrodos epicárdicos. Métodos. En 29 corazones aislados de conejo se obtienen registros de la fibrilación ventricular con un electrodo múltiple situado en la pared libre del ventrículo izquierdo. Se comparan los parámetros obtenidos en el dominio de la frecuencia (análisis de Fourier) al utilizar electrodos unipolares o bipolares con varias separaciones entre los electrodos en distintas direcciones (horizontal, vertical o diagonales). Resultados. La modalidad de registro (unipolar o bipolar) y la separación entre los electrodos han introducido diferencias significativas en la frecuencia media (p < 0,0001) y en la energía normalizada del espectro alrededor de la frecuencia dominante (± 1 Hz) (p < 0,05), pero éstas han sido mínimas al considerar la frecuencia dominante. En el análisis espectral cruzado, se ha observado que la coherencia entre los registros unipolares disminuye al aumentar la separación entre los electrodos, mientras que ocurre lo contrario al analizar la coherencia entre los unipolares y los bipolares. Ambas coherencias se correlacionan inversamente, de tal modo que cuanto mayor es la primera menor es la de los unipolares respecto a los bipolares (r = 0,29; p < 0,0001; n = 348). Conclusiones. El tipo de registro utilizado (unipolar o bipolar) introduce variaciones en la información obtenida mediante técnicas espectrales en los registros epicárdicos de la fibrilación ventricular. Estas diferencias se observan en la frecuencia media y en la distribución de frecuencias del espectro, pero son muy pequeñas al considerar la frecuencia dominante (AU)

Introduction and objectives. The aim of this study was to examine the hypothesis that the recording mode (i.e., 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 multiple-electrode 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 (i.e., horizontal, vertical or diagonal) were compared. Results. Changing the recording mode (i.e., 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 two 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 (i.e., unipolar or bipolar) used influenced the information obtained using spectral analysis techniques from epicardial recordings of ventricular fibrillation. Differences were observed in the mean frequency and in the frequency distribution, but they were very small relative to the dominant frequency (AU)

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. METHODS: In 31 Langendorff-perfused rabbit hearts, the characteristics and inducibility of VF were analyzed before and after the induction of RF lesions comprising: (1) the posterior zone of the septum and of the walls of both ventricles (n = 10); (2) the anterior zone of the septum and of the walls of both ventricles (n = 11); and (3) the midseptal zone (n = 10). RESULTS: Complete isolation of the zone encompassed by the lesions was obtained in 5, 6, and 5 experiments of series 1, 2, and 3, respectively. In these experiments, the arrhythmia was only induced from within the zone encompassed by the lesions in one experiment belonging to series 2 (P < 0.05 with respect to baseline). In contrast, in all but one of the cases in series 2, VF could be induced from outside the isolated zone (ns vs baseline). Partial isolation was obtained in five experiments of each series. In these experiments, on pacing from within the partially isolated zone, sustained VF was not induced in any experiment (P < 0.05 with respect to baseline), while in all cases VF could be induced on pacing from the external zone (ns vs baseline). CONCLUSION: In the experimental model used, the three zones studied were not essential for maintaining VF. In most cases, their partial or total isolation avoided inducibility of the arrhythmia in those zones, though not in the remaining myocardium.

[Effect of flecainide on longitudinal and transverse conduction velocities in ventricular myocardium. An experimental study]. / Efectos de la flecainida sobre las velocidades de conducción longitudinal y transversal en el miocardio ventricular. Estudio experimental.

It is known that the effect of flecainide on longitudinal and transverse ventricular conduction velocities depends on the coupling interval. If this is so, whether the longitudinal or transverse direction is predominantly affected could depend on the magnitude of the coupling interval. In order to investigate this hypothesis, we studied the effect of flecainide, 1 micromol/L, on conduction velocities in excised heart preparations from 11 rabbits using a basal cycle length of 250 ms and inserting two extrastimuli at a decreasing coupling interval. Flecainide significantly reduced both conduction velocities. However, the effect increased as the coupling interval decreased for only the longitudinal velocity. At long coupling intervals, flecainide produced a greater reduction in transverse than longitudinal velocity, whereas, at short intervals, both velocities were affected similarly.

Efectos de la flecainida sobre las velocidades de conducción longitudinal y transversal en el miocardio ventricular. Estudio experimental / Effect of flecainide on longitudinal and transverse conduction velocities in ventricular myocardium. An experimental study

Es conocido que el efecto de la flecainida sobre las velocidades de conducción ventricular longitudinal y transversal depende del acoplamiento entre estímulos. Si esto es así, el predominio de los efectos en sentido longitudinal frente al transversal puede variar en función de dicho acoplamiento. Con el objetivo de analizar dicha hipótesis, se ha estudiado el efecto de la flecainida (1 µmol/l) sobre dichas velocidades de conducción en 11 preparaciones de corazón aislado de conejo, para lo que se ha utilizado un tren base de estimulación de 250 ms y se han acoplado 2 extraestímulos con acoplamiento decreciente. La flecainida ha reducido ambas velocidades de forma significativa. Este efecto se ha incrementado al reducir el acoplamiento únicamente en el caso de la velocidad longitudinal. Con acoplamientos largos, la flecainida ha producido una mayor reducción de la velocidad transversal que de la longitudinal, mientras que para intervalos cortos ha afectado en la misma proporción a ambas velocidades

It is known that the effect of flecainide on longitudinal and transverse ventricular conduction velocities depends on the coupling interval. If this is so, whether the longitudinal or transverse direction is predominantly affected could depend on the magnitude of the coupling interval. In order to investigate this hypothesis, we studied the effect of flecainide, 1 µmol/L, on conduction velocities in excised heart preparations from 11 rabbits using a basal cycle length of 250 ms and inserting two extrastimuli at a decreasing coupling interval. Flecainide significantly reduced both conduction velocities. However, the effect increased as the coupling interval decreased for only the longitudinal velocity. At long coupling intervals, flecainide produced a greater reduction in transverse than longitudinal velocity, whereas, at short intervals, both velocities were affected similarly

[Time-frequency analysis of ventricular fibrillation. An experimental study]. / 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.

Análisis tiempo-frecuencia de la fibrilación ventricular. Estudio experimental / Time-frequency analysis of ventricular fibrillation. An experimental study

Introducción y objetivos. El análisis de la variabilidad de la frecuencia durante la fibrilación ventricular ha aportado resultados no uniformes. En un modelo experimental de fibrilación ventricular se analiza, en una escala temporal reducida, las variaciones de la frecuencia y su distribución espacial. Métodos. En 10 preparaciones de corazón aislado y perfundido de conejo, se efectúan registros epicárdicos de la fibrilación ventricular con un electrodo múltiple (240 electrodos unipolares) y se aplican métodos de análisis espectrales y de tiempo-frecuencia para obtener la frecuencia dominante en la pared anterolateral del ventrículo izquierdo. Resultados. La recta de regresión obtenida al relacionar los valores de la frecuencia dominante obtenidos con los 2 métodos de análisis muestra una buena correlación entre ambos: frecuencia (método espectral) = 1,01 × frecuencia (método tiempo-frecuencia) -­ 0,4 (r = 0,9; p < 0,0001; error estándar de la estimación, 2,2 Hz). Las variaciones temporales de la frecuencia dominante en una escala de tiempo reducida (análisis de tiempo-frecuencia) son significativas en todos los casos excepto en uno y muestran un coeficiente de variación comprendido entre 0,19 ± 0,06 y 0,24 ± 0,07 (NS). En todos los casos se observan diferencias regionales significativas, aunque la ubicación de los valores más altos varía según el instante considerado, con un predominio en las zonas apicales y anteriores. Conclusiones. En ausencia de factores moduladores externos, la fibrilación ventricular presenta variaciones temporales y espaciales de la frecuencia que se objetivan en escalas de tiempo reducidas. En la pared libre del ventrículo izquierdo, la frecuencia dominante es mayor en las zonas apicales y anteriores, zonas en las que se ubican con mayor frecuencia los valores máximos (AU)

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 × 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 (AU)

Modification of ventricular fibrillation activation patterns induced by local stretching.

INTRODUCTION: We hypothesize that local modifications in electrophysiological properties, when confined to zones of limited extent, induce few changes in the global activation process during ventricular fibrillation (VF). To test this hypothesis, we produced local electrophysiological modifications by stretching a circumscribed zone of the left ventricular wall in an experimental model of VF. METHODS AND RESULTS: In 23 Langendorff-perfused rabbit hearts frequency, time-frequency and time-domain techniques were used to analyze the VF recordings obtained with two epicardial multiple electrodes before, during, and after local stretching produced with a left intraventricular device. Acute local stretching accelerated VF in the stretched zone reversibly and to a variable degree, depending on the magnitude of stretch and the time elapsed from its application. In the half time (5 minutes) of the analyzed period, a longitudinal lengthening of 12.1 +/- 4.5% (vertical axis) and 11.8 +/- 6.2% (horizontal axis) in the stretched zone produced an increase in the dominant frequency (DFr) (15.2 +/- 1.9 versus 18.8 +/- 2.5 Hz, P < 0.0001), a decrease in mean VV interval (63 +/- 8 versus 53 +/- 6 msec, P < 0.001), and an increase in the complexity of the activation maps-with more areas of conduction block and more breakthrough patterns (23% versus 37%, P < 0.01), without significant changes in the percentages of complete reentry patterns (9% versus 9%, ns). Simultaneously, in the nonstretched zone, no variations were observed in the DFr (15.2 +/- 2.1 versus 15.3 +/- 2.5 Hz, ns), mean VV intervals (66 +/- 8 versus 65 +/- 8 msec, ns), or types and percentages of maps with breakthrough (25% versus 20%, ns) or reentry patterns (12% versus 8%, ns). No significant correlation was observed between the DFr in the two zones (R = 0.24, P = 0.40). CONCLUSION: Local stretching increases the electrophysiological heterogeneity of myocardium and accelerates and increases the complexity of VF in the stretched area, without significantly modifying the occurrences of the types of VF activation patterns in the nonstretched zone.

Significance of the morphological patterns of electrograms recorded during ventricular fibrillation: an experimental study.

Mapping techniques are used to study the significance of the morphological patterns of the electrograms (EGMs) obtained during VF in an experimental model. In 24 isolated rabbit heart preparations recordings were made of activation during VF using a multiple electrode (121 unipolar electrodes) positioned on the lateral wall of the left ventricle. Three types of activation maps were selected: (A) with functional block of an activation front; (B) with epicardial breakthrough; and (C) with a single broad wavefront without block lines. The EGMs were classified as negative (Q), positive-negative with a predominance of the negative (rS) or positive wave (Rs), and positive (R). In 60 type A maps the morphology in the zone limiting the block line corresponded to an R wave in 55 (92%) cases and to Rs in 5 (8%) cases. In 67 type B maps, the EGM in the earliest activation zone most often showed Q wave morphology (48 [72%] cases), followed by rS (18 [27%] cases), and Rs morphology (1 [1%] case); in no case was R wave morphology seen. Finally, in 78 type C maps the morphology corresponded to a Q wave in 15 (19%) cases, rS in 38 (49%), Rs in 24 (31%), and R in a 1 (1%) case. The differences between the three types of maps were significant (P < 0.0001). Q wave EGM sensitivity for indicating the existence of an epicardial breakthrough pattern was 72%, with a specificity of 89%, and positive and negative predictive values of 76% and 87%, respectively. R wave EGM sensitivity for indicating the existence of conduction block was 92%, with a specificity of 99%, and positive and negative predictive values of 98% and 97%, respectively. R wave morphology is highly sensitive and specific for indicating conduction block. EGM recordings with initial positivity predominance are infrequent in the earliest activation zones of epicardial breakthrough during VF. The recording of the EGM with Q wave morphology indicates centrifugal activation from the explored zone.

[Effects of myocardial stretching on excitation frequencies determined by spectral analysis during ventricular fibrillation]. / Efecto del estiramiento micárdico sobre las frecuencias de activación determinadas mediante análisis espectral durante la fibrilación ventricular.

INTRODUCTION AND OBJECTIVES: The aim of this study was to analyze the effects of myocardial stretching on excitation frequencies, as determined by spectral analysis, during ventricular fibrillation. METHODS: In 12 isolated rabbit heart preparations, ventricular activation during ventricular fibrillation was recorded with multiple electrodes. Recordings were obtained before, during and after ventricular dilatation produced with an intraventricular balloon. The dominant frequency of the signals obtained with each of the electrodes was determined by spectral analysis. RESULTS: During the control phase, the mean, minimum and maximum dominant frequencies were, respectively, 14.3 1.7, 12.5 1.7, and 16.2 1.4 Hz, and the average difference between the maximum and minimum frequencies was 3.6 2.1 Hz. This difference was over 4 Hz in four cases, and in no case did it exceed 8 Hz. During ventricular stretching, the mean dominant frequency increased significantly (21.1 6.1 Hz; p < 0.0001), as did the minimum values (14 2.6 Hz; p < 0.05) and especially the maximum values (26.6 7.7 Hz; p < 0.0001). The difference between the maximum and minimum frequencies (12.6 6.4 Hz; p < 0.001) was over 4 Hz in all cases except one, and over 8 Hz in 9 cases. The maximum values were distributed heterogeneously during ventricular stretching. Upon suppressing ventricular stretching, the dominant frequency did not differ from controls. CONCLUSIONS: Myocardial frequency maps during ventricular fibrillation show limited variations in the dominant frequency of the signals recorded in the lateral wall of the left ventricle. During stretching, the patterns were heterogeneous, due mainly to the marked increase in the maximum dominant frequency. In the experimental model used, the effects of stretching remitted after suppressing ventricular dilatation.