Estudio experimental de los efectos de EIPA, losartán y BQ-123 sobre las modificaciones electrofisiológicas inducidas por el estiramiento miocárdico / Experimental study of the effects of EIPA, Losartan, and BQ-123 on electrophysiological changes induced by myocardial stretch

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 de los receptores de la angiotensina II, losartán (1 miM, n = 8); durante la perfusión del bloqueador del receptor de la endotelina A, BQ-123 (0,1 miM, n = 9), y durante la perfusión del inhibidor del intercambiador Na+/H+, EIPA (5-[N-ethyl-N-isopropyl]-amiloride) (1 miM, n = 9). Resultados: EIPA atenuó el aumento de la frecuencia dominante de la fibrilación producido por el estiramiento (control = 40,4%; losartán = 36% [no significativo]; BQ-123 = 46% [no significativo], y EIPA = 22% [p < 0,001]). Durante el estiramiento, la complejidad de los mapas de activación fue menor en la serie con EIPA (p < 0,0001) y también en esta serie fue mayor la concentración espectral de la arritmia (mayor regularidad): control = 18 ± 3%; EIPA = 26 ± 9% (p < 0,02); losartán = 18 ± 5% (no significativo), y BQ-123 = 18 ± 4% (no significativo). Conclusiones: El inhibidor del intercambiador Na+/H+ EIPA atenúa los efectos electrofisiológicos responsables de la aceleración y del aumento de la complejidad de la fibrilación ventricular producidos por el estiramiento agudo miocárdico. Por el contrario, el antagonista de los receptores de la angiotensina II, losartán, y el del receptor A de la endotelina, BQ-123, no modifican estos efectos (AU)

Introduction and objectives: Mechanical response to myocardial stretch has been explained by various mechanisms, which include Na+ /H+ exchanger activation by autocrine-paracrine system activity. Drug-induced changes were analyzed to investigate the role of these mechanisms in the electrophysiological responses to acute myocardial stretch. Methods: Multiple epicardial electrodes and mapping techniques were used to analyze changes in ventricular fibrillation induced by acute myocardial stretch in isolated perfused rabbit hearts. Four series were studied: control (n = 9); during perfusion with the angiotensin receptor blocker losartan (1 mM, n = 8); during perfusion with the endothelin A receptor blocker BQ-123 (0.1 mM, n = 9), and during perfusion with the Na+ /H+ exchanger inhibitor EIPA (5-[N-ethyl-N-isopropyl]-amiloride) (1 mM, n = 9). Results: EIPA attenuated the increase in the dominant frequency of stretch-induced fibrillation (control = 40.4%; losartan = 36% [not significant]; BQ-123 = 46% [not significant]; and EIPA = 22% [P < .001]). During stretch, the activation maps were less complex (P < .0001) and the spectral concentration of the arrhythmia was greater (greater regularity) in the EIPA series: control = 18 (3%); EIPA = 26 (9%) (P < .02); losartan = 18 (5%) (not significant); and BQ-123 = 18 (4%) (not significant). Conclusions: The Na+ /H+ exchanger inhibitor EIPA attenuated the electrophysiological effects responsible for the acceleration and increased complexity of ventricular fibrillation induced by acute myocardial stretch. The angiotensin II receptor antagonist losartan and the endothelin A receptor blocker BQ-123 did not modify these effects (AU)

Experimental Study of the Effects of EIPA, Losartan, and BQ-123 on Electrophysiological Changes Induced by Myocardial Stretch.

INTRODUCTION AND OBJECTIVES: Mechanical response to myocardial stretch has been explained by various mechanisms, which include Na(+)/H(+) exchanger activation by autocrine-paracrine system activity. Drug-induced changes were analyzed to investigate the role of these mechanisms in the electrophysiological responses to acute myocardial stretch. METHODS: Multiple epicardial electrodes and mapping techniques were used to analyze changes in ventricular fibrillation induced by acute myocardial stretch in isolated perfused rabbit hearts. Four series were studied: control (n = 9); during perfusion with the angiotensin receptor blocker losartan (1 µM, n = 8); during perfusion with the endothelin A receptor blocker BQ-123 (0.1 µM, n = 9), and during perfusion with the Na(+)/H(+) exchanger inhibitor EIPA (5-[N-ethyl-N-isopropyl]-amiloride) (1 µM, n = 9). RESULTS: EIPA attenuated the increase in the dominant frequency of stretch-induced fibrillation (control=40.4%; losartan=36% [not significant]; BQ-123=46% [not significant]; and EIPA=22% [P<.001]). During stretch, the activation maps were less complex (P<.0001) and the spectral concentration of the arrhythmia was greater (greater regularity) in the EIPA series: control=18 (3%); EIPA = 26 (9%) (P < .02); losartan=18 (5%) (not significant); and BQ-123=18 (4%) (not significant). CONCLUSIONS: The Na(+)/H(+) exchanger inhibitor EIPA attenuated the electrophysiological effects responsible for the acceleration and increased complexity of ventricular fibrillation induced by acute myocardial stretch. The angiotensin II receptor antagonist losartan and the endothelin A receptor blocker BQ-123 did not modify these effects.

Evaluación de la complejidad de la activación miocárdica durante la fibrilación ventricular. Estudio experimental / Evaluation of the complexity of myocardial activation during ventricular fibrillation. An experimental study

Introducción y objetivos. Analizar en un modelo experimental las características de la fibrilación ventricular en situaciones con distintos grados de complejidad y establecer la relación existente entre los datos aportados por distintos métodos de análisis de la arritmia. Métodos. En 27 preparaciones de corazón aislado de conejo estudiadas bajo la acción de fármacos (propranolol y KB-R7943) o procedimientos físicos (estiramiento) que causan distintos grados de variación de la complejidad de la activación miocárdica durante la arritmia, se han utilizado técnicas espectrales, morfológicas y cartográficas para procesar los registros obtenidos con multielectrodos epicárdicos. Resultados. La complejidad de la fibrilación ventricular objetivada mediante procedimientos cartográficos se ha relacionado con la frecuencia dominante, la energía normalizada del espectro, el índice de regularidad de las señales, sus coeficientes de variación y el área de las regiones de interés identificadas a partir de estos parámetros. En el análisis multivariable, se han aceptado como variables independientes el área de las regiones de interés relacionadas con la energía espectral y el coeficiente de variación de la energía (índice de complejidad = -0,005 × área de las regiones de la energía espectral -2,234 × coeficiente de variación de la energía +1,578; p = 0,0001; r = 0,68). Conclusiones. Los indicadores espectrales, morfológicos y, de manera independiente, los derivados del análisis de las regiones de interés de la energía normalizada permiten aproximarse de manera fiable a la evaluación de la complejidad de la fibrilación ventricular como una alternativa a los complejos procedimientos cartográficos (AU)

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 (AU)