42 research outputs found
Efectos electrofisiológicos miocárdicos intrínsecos producidos por la inhibición del sistema de intercambio sodio-protón, en condiciones de normoxia, y tras la isquemia miocárdica regional. Estudio experimental.
RESUMEN
Hemos investigado: 1) los efectos protectores del intercambiador sodio-protón (NHE), con el 5-(N-etil-N-isopropil) amiloride (EIPA), a concentración 0.4 M, sobre la inducibilidad de la fibrilación ventricular (FV), y sobre la refractariedad miocárdica ventricular, tras la oclusión arterial coronaria; 2) los efectos electrofisiológicos intrínsecos producidos por la inhibición del NHE, administrando EIPA 0.4 y 1 M, en condiciones de normal oxigenación, sobre el automatismo sinusal, la conducción sinoauricular y auriculoventricular (AV), y sobre la refractariedad auricular, ventricular, y del sistema de conducción AV; y 3) los efectos electrofisiológicos miocárdicos intrínsecos producidos por la inhibición del NHE, con EIPA 0.4 y 1 M, sobre la frecuencia dominante (FD) de la FV inducida, en condiciones de normoxia, como característica electrofisiológica estrechamente relacionada con la refractariedad ventricular.
Todos los experimentos se realizaron en corazón aislado y perfundido de conejo (preparación tipo Langendorff). Para conseguir el primer objetivo aplicamos el test del extraestímulo (TEE) ventricular con uno, dos, y tres extraestímulos, para tratar de inducir la FV. La aplicación del primer extraestímulo sirvió además para establecer el periodo refractario objeto de investigación. Las determinaciones se realizaron previamente y tras la oclusión arterial coronaria circunfleja, en dos grupos de experimentos: control y tratados con EIPA 0.4 M.
Para cumplimentar el segundo objetivo analizamos:
a) periodos refractarios efectivo y funcional auricular y del sistema de conducción AV mediante el TEE auricular, periodos refractarios efectivo y funcional ventricular mediante el TEE ventricular; b) automatismo sinusal mediante la determinación de la longitud del ciclo sinusal y del tiempo de recuperación del nodo sinusal; y c) tiempo de conducción sinoauricular con el test de Narula, conducción AV y conducción ventriculoauricular retrógrada, mediante la medición de la longitud del ciclo de Wenckebach y la longitud del ciclo de Wenckebach retrógrado respectivamente. Finalmente, para acometer el tercer objetivo analizamos, por el método de Welch, la FD media, máxima y mínima de la FV inducida por estimulación a frecuencias crecientes. Los parámetros citados se estudiaron en situación control e inhibiendo el NHE, con EIPA. Utilizamos dos concentraciones de dicho inhibidor: 0.4 y 1 M; la primera se halla en el rango de la IC50 para el NHE y la segunda es la concentración más comúnmente usada en los estudios de protección miocárdica.
La inhibición del NHE con EIPA 0.4 M protegió al miocardio isquémico, al dificultar la inducibilidad de la FV. Este efecto protector, probablemente está relacionado, al menos en parte, con el mantenimiento de la refractariedad ventricular en el miocardio isquémico, lo cual ha sido también observado en el presente trabajo. Excepto para el caso del periodo refractario efectivo del sistema de conducción AV, que aumentó ligeramente con EIPA 1 M, la inhibición del NHE con EIPA 0.4 y 1 M en condiciones de normal oxigenación, no modificó la refractariedad intrínseca ventricular, auricular, ni del sistema de conducción AV, así como tampoco la FD de la FV inducida, mientras que deprimió ligeramente el cronotropismo sinusal y la conducción AV, si bien estos últimos podrían ser efectos secundarios, relacionados con la capacidad depresora del automatismo sinusal y la conducción AV que ejerce el amiloride, precursor del EIPA.
El hecho de que la inhibición del NHE, manifestara efectos electrofisiológicos antiarrítmicos intrínsecos sobre el miocardio isquémico, impidiendo la caída de la refractariedad, y no ejerciera ninguna modificación electrofisiológica, en condiciones de normal oxigenación, sobre la refractariedad y la FD de la FV, propiedades ligadas a la aparición de arritmias por reentrada, coincide con lo relatado por diversos investigadores acerca del escaso, sino nulo, papel del NHE en situación fisiológica y su importancia en circunstancias fisiopatológicas como la isquemia.
__________________________________________________________________________________________________We have investigated the protective effects of the sodium-proton exchanger (NHE) inhibition using 5-(N-ethyl-N-isopropyl) amiloride (EIPA) 0.4 M, on the incidence of induced ventricular fibrillation (VF), and on intrinsic ventricular refractoriness, after circumflex coronary artery occlusion. Experiments were performed on isolated rabbit heart. To induce VF extrastimulus test with one, two and three extrastimuli, was used; the first extrastimulus application also served to determine refractory periods. Parameters were determined previously and after coronary occlusion, in both control and EIPA 0.4 M treated groups. In order to investigate whether the NHE inhibition produces some myocardial intrinsic electrophysiological effect, we have also investigated using EIPA, 0.4 and 1 M, in normoxic condition: a) the sinus cycle length and sinus node recovery time, as an automatism index; b) the sinoatrial conduction (Narulas test), and atrioventricular (AV) and ventricleatrial conduction, by anterograde and retrograde Wenckebach cycle length determination respectively; c) atrial, ventricular, and AV conduction system, effective and functional refractory periods using the extrastimulus test; and d) mean, minimum and maximum dominant frequency (DF) of VF by the Welchs method, which are properties closely related with ventricular refractoriness.
NHE inhibition with 0.4 M protected the ischemic myocardium, decreasing VF inducibility, at least in part, by the maintenance of ischemic myocardium refractoriness, observed in this study. No modification on refractoriness was observed, in normoxic conditions, except an AV conduction system effective refractory period increase, with EIPA 1 M. The DF of VF was either not modified. EIPA 0.4 and 1 M also slightly depressed sinus chronotropism and AV conduction
Development and Long-Term Follow-Up of an Experimental Model of Myocardial Infarction in Rabbits
[EN] A chronic model of acute myocardial infarction was developed to study the mechanisms involved in adverse postinfarction ventricular remodeling. In an acute myocardial infarction (AMI), the left circumflex coronary artery of New Zealand White rabbits (n = 9) was occluded by ligature for 1 h, followed by reperfusion. A specific care protocol was applied before, during, and after the intervention, and the results were compared with those of a sham operated group (n = 7). After 5 weeks, programmed stimulation and high-resolution mapping were performed on isolated and perfused hearts using the Langendorff technique. The infarct size determined by 2,3,5-triphenyltetrazolium chloride inside of the area at risk (thioflavin-S) was then determined. The area at risk was similar in both groups (54.33% (experimental infarct group) vs. 58.59% (sham group), ns). The infarct size was 73.16% as a percentage of the risk area. The experimental infarct group had a higher inducibility of ventricular arrhythmias (100% vs. 43% in the sham group, p = 0.009). A reproducible chronic experimental model of myocardial infarction is presented in which the extent and characteristics of the lesions enable the study of the vulnerability to develop ventricular arrhythmias because of the remodeling process that occurs during cardiac tissue repair.This research was funded by Generalitat Valenciana (PROMETEO/2018/078), Instituto de Salud Carlos III (CB16/11/00486; PI15/01408; PIE15/0001 3and PI18/01620) to F.J.C.Genovés, P.; Arias-Mutis, ÓJ.; Parra, G.; Such-Miquel, L.; Zarzoso, M.; Del Canto, I.; Soler, C.... (2020). Development and Long-Term Follow-Up of an Experimental Model of Myocardial Infarction in Rabbits. Animals. 10(9). https://doi.org/10.3390/ani1009157610
The training-induced changes on automatism, conduction and myocardial refractoriness are not mediated by parasympathetic postganglionic neurons activity
The purpose of this study is to test the role that parasympathetic postganglionic neurons could play on the adaptive electrophysiological changes produced by physical training on intrinsic myocardial automatism, conduction and refractoriness. Trained rabbits were submitted to aphysical training protocol on treadmill during 6 weeks. The electrophysiological study was performed in an isolated heart preparation. The investigated myocardial properties were: (a) sinus automatism, (b) atrioventricular and ventriculoatrial conduction, (c) atrial, conduction system and ventricular refractoriness. The parameters to study the refractoriness were obtained by means of extrastimulus test at four diVerent pacing cycle lengths (10% shorter than spontaneous sinus cycle length, 250, 200 and 150 ms) and (d) mean dominant frequency (DF) of the induced ventricular Wbrillation (VF), using a spectral method. The electrophysiological protocol was performed before and during continuous atropine administration (1 ¿M), in order to block cholinergic receptors. Cholinergic receptor blockade did not modify either the increase in sinus cycle length, atrioventricular conduction and refractoriness (left ventricular and atrioventricular conduction system functional refractory periods) or the decrease of DF of VF. These Wndings reveal that the myocardial electrophysiological modiWcations produced by physical training are not mediated by intrinsic cardiac parasympathetic activity.The authors thank Carmen Rams, Ana Diaz, Pilar Navarro and Cesar Avellaneda for their excellent technical assistance. This work has been supported by grants from the Spanish Ministry of Education and Science (DEP2007-73234-C03-01) and Generalitat Valenciana (PROMETEO 2010/093). M Zarzoso was supported by a research scholarship from Generalitat Valenciana (BFPI/2008/003).Zarzoso Muñoz, M.; Such Miquel, L.; Parra Giraldo, G.; Brines Ferrando, L.; Such, L.; Chorro, F.; Guerrero, J.... (2012). The training-induced changes on automatism, conduction and myocardial refractoriness are not mediated by parasympathetic postganglionic neurons activity. European Journal of Applied Physiology. 112(6):2185-2193. https://doi.org/10.1007/s00421-011-2189-4S218521931126Armour JA, Hopkins DA (1990a) Activity of in vivo canine ventricular neurons. Am J Physiol Heart Circ Physiol 258:H326–H336. doi: 10.1152/ajpregu.00183.2004Armour JA, Hopkins DA (1990b) Activity of canine in situ left atrial ganglion neurons. Am J Physiol Heart Circ Physiol 259:H1207–H1215Armour JA (2004) Cardiac neuronal hierarchy in health and disease. 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Análisis de regularidad en fibrilación ventricular: aplicación a registros de mapeado cardíaco
Las técnicas utilizadas en el análisis de la señal de fibrilación
ventricular (FV), obtenida mediante sistemas de mapeado
utilizando matrices de electrodos, extraen información del
proceso a partir de parámetros calculados principalmente en el
dominio del tiempo o de la frecuencia. El presente trabajo
plantea la aplicación del índice de regularidad (IR), propuesto
inicialmente para caracterizar la fibrilación auricular humana,
a la señal de FV en un modelo experimental de corazón animal.
Los resultados obtenidos muestran que el IR permite extraer
información de los mapas de FV no disponible de forma directa
cuando se estudian mediante los métodos clásicos en el tiempo o
la frecuencia, cuantificando el grado de modificación en la
morfología de las ondas de activación durante la FV
Effect of chronic exercise on myocardial electrophysiological heterogeneity and stability. Role of intrinsic cholinergic neurons: A study in the isolated rabbit heart
[EN] A study has been made of the effect of chronic exercise on myocardial electrophysiological heterogeneity and stability, as well as of the role of cholinergic neurons in these changes. Determinations in hearts from untrained and trained rabbits on a treadmill were performed. The hearts were isolated and perfused. A pacing electrode and a recording multielectrode were located in the left ventricle. The parameters determined during induced VF, before and after atropine (1 mu M), were: fibrillatory cycle length (VV), ventricular functional refractory period (FRPVF), normalized energy (NE) of the fibrillatory signal and its coefficient of variation (CV), and electrical ventricular activation complexity, as an approach to myocardial heterogeneity and stability. The VV interval was longer in the trained group than in the control group both prior to atropine (78 +/- 10 vs. 68 +/- 10 ms) and after atropine (76 +/- 8 vs. 67 +/- 10 ms). Likewise, FRPVF was longer in the trained group than in the control group both prior to and after atropine (53 +/- 8 vs. 42 +/- 7 ms and 50 +/- 6 vs. 40 +/- 6 ms, respectively), and atropine did not modify FRPVF. The CV of FRPVF was lower in the trained group than in the control group prior to atropine (12.5 +/- 1.5% vs. 15.1 +/- 3.8%) and, decreased after atropine (15.1 +/- 3.8% vs. 12.2 +/- 2.4%) in the control group. The trained group showed higher NE values before (0.40 +/- 0.04 vs. 0.36 +/- 0.05) and after atropine (0.37 +/- 0.04 vs. 0.34 +/- 0.06; p = 0.08). Training decreased the CV of NE both before (23.3 +/- 2% vs. 25.2 +/- 4%; p = 0.08) and after parasympathetic blockade (22.6 +/- 1% vs. 26.1 +/- 5%). Cholinergic blockade did not modify these parameters within the control and trained groups. Activation complexity was lower in the trained than in the control animals before atropine (34 +/- 8 vs. 41 +/- 5), and increased after atropine in the control group (41 +/- 5 vs. 48 +/- 9, respectively). Thus, training decreases the intrinsic heterogeneity of the myocardium, increases electrophysiological stability, and prevents some modifications due to muscarinic block.This research was supported by the Spanish Ministry of Education and Science, (DEP2007-73234-C03-01 to AMA), http://www.mecd.gob.es/portada-mecd/; and the Generalitat Valenciana (PROMETEO 2010/093 to FJC, and FPI/2008/003 to MZ), http://www.gva.es/va/inicio/presentacion; jsessionid=ydprbDQZTsCTz85W1Such-Miquel, L.; Brines-Ferrando, L.; Alberola, A.; Zarzoso Muñoz, M.; Chorro Gasco, FJ.; Guerrero-Martínez, JF.; Parra-Giraldo, G.... (2018). Effect of chronic exercise on myocardial electrophysiological heterogeneity and stability. Role of intrinsic cholinergic neurons: A study in the isolated rabbit heart. 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Application of machine learning techniques to analyse the effects of physical exercise in ventricular fibrillation
This work presents the application of machine learning techniques to analyze the influence of physical exercise in the heart's physiological properties, during ventricular fibrillation. With that purpose, different kinds of classifiers (linear and neural models) were used to classify between trained and sedentary rabbit hearts. These classifiers were used to perform knowledge extraction through a wrapper feature selection algorithm. The obtained results showed the higher performance of the neural models compared to the linear classifier (higher performance measures and higher dimensionality reduction). The most relevant features to describe the benefits of physical exercise are those related to myocardial heterogeneity, mean activation rate and activation complexity
Analysis of spatial and temporal evolution of regularity maps during ventricular fibrillation
The analysis of cardiac mapping allows investigating
the structure of ventricular fibrillation (VF). This work
analyzes regions of interest (ROI) on cardiac maps
obtained from the regularity analysis of VF records,
providing information about signal regularity at each
time instant and its spatial distribution.
Cardiac registers were obtained using a 240-
electrodes matrix located on left ventricle of isolated
rabbit heart. A Langendorff system was used to maintain
the heart perfusion. VF was induced by increased
frequencies. Two groups of records were considered:
control (G1: without physical training, N=10), and
trained (G2, N=9).
Records were processed in consecutive 4-second
segments. Regularity index (RI) was obtained for every
segment and channel. RI is a measure of similarity
degree among local activation waves for every channel.
A map with the RI value of each channel was computed
for the 82 register segments.
To analyze the spatial distribution of RI, a threshold
value was determined experimentally and applied to the
map in order to obtain the ROI. Two parameters were
calculated: ROI spatial number (ROIsn, a measure of
spatial fragmentation), and ROI spatial area (ROIsa, the
percentage of area map occupied by ROI).
In case of the time course of ROI, two additional
parameters were computed: the number of electrodes
which value had changed respect to the threshold in two
consecutive maps (ROIen, which is related with the
change size), and the cumulative absolute differences of
RI values for the electrodes which are changed (ROIed).
Obtained results for spatial analysis show that the
number of ROI is lower for trained rabbits (ROIsn; G1:
4.465±1.120; G2: 2.,227±0.623; p<0.001), but ROI
spatial area is greater than the control group (ROIsa;
G1: 76.235±5.355%; G2: 88.163±2.885%; p<0.001).
Time-course analysis shows that more electrodes change
between consecutive maps in the control group (ROIen,
G1: 22.455±6.702; G2: 13.877±2.485; p<0.001). No
significant differences were found for ROIed (G1:
18.509±6.932; G2: 18.619±4.196; n.s.).
To conclude, ROI analysis on RI maps applied to
trained and no trained rabbits groups shows that VF
cardiac response is more irregular and spatially
fragmented in no trained group. In addition, regularity
maps are more stable with time in trained group
Modifications on regularity and spectrum of ventricular fibrillation signal induced by physical training
The objective of this work is to study the modifications
on cardiac response during ventricular fibrillation (VF)
induced by physical training. The analysis was performed
in the frequency domain of VF, and the regularity of the
signal was also considered.
Two sets of records were acquired: control (G1:
without physical training, N=10), and trained (G2, N=9).
Cardiac registers were obtained using a 240-electrodes
matrix located on left ventricle of isolated rabbit heart. A
Langendorff system was used to maintain the heart
perfusion. VF was induced by increased frequencies.
To analyze the time course of VF, records were
processed in 4-second segments. For every segment and
channel, Welch periodogram with Hanning window, two
non-overlapped sections and zero padding, was
computed. Parameters considered in frequency domain
are: dominant frequency (DF) and normalized energy
(NE: spectral energy in the window DF±1Hz, normalized
by spectral energy in 5-35Hz band).
For every segment and channel, a regularity analysis
of VF was performed, obtaining the regularity index (RI),
which is a measure of similarity among local activation
waves present in every channel.
Mean values for the parameters (DF, NE and RI) of
the whole set of electrodes were computed for every
segment. Obtained results show that DF is lower for
trained rabbits (G1: 18.234±1, 241Hz; G2: 14.370±0,
866Hz; p<0.001). NE is greater for this group (G1:
0.140±0.006; G2: 0.263±0.017; p<0.001), suggesting a
greater spectral concentration around DF. Finally, a
greater regularity has been observed in the fibrillation
signal for trained group (IR, G1: 0.756±0.026; G2:
0.834±0.014; p<0.001).
As a summary, the results suggest that both spectral
characteristics and regularity of VF signal are clearly
different for G1 and G2 groups. The trained group (G2)
shows greater regularity, lower DF and spectral
dispersion. These factors should be interpreted as a more
stable cardiac response to V
Relación entre el espectro y la regularidad en la señal de fibrilación ventricular modificada por el ejercicio físico
El presente trabajo estudia las modificaciones intrínsecas que el
ejercicio físico produce en la respuesta cardíaca durante la FV.
Se han calculado dos parámetros relacionados con el espectro
de la señal (FD: frecuencia dominante, y EN: energía
normalizada), y otro relacionado con la regularidad de las OAL
(IR: índice de regularidad), Se ha realizado un análisis de
correlación entre los tres parámetros para valorar su grado de
complementariedad.
Se consideraron dos grupos de conejos: control (G1: sin
entrenamiento, N=10) y entrenados (G2, N=9). Se utilizó un
electrodo matricial de 240 canales localizado en ventrículo
izquierdo de corazón aislado de conejo perfundido mediante un
sistema de Langendorff. La FV se indujo por estimulación a
frecuencias crecientes.
Los resultados muestran que el grupo entrenado presenta una
mayor regularidad de la señal (IR: G1: 0,757+-0,091; G2:
0,845+-0,084; p<0.001), así como menor FD (G1:
18.23±2.96Hz; G2: 14.13+-1.73Hz; p<0.001) y dispersión
espectral (EN: G1: 0,138+-0.105; G2: 0,293+-0,176; p<0.001).
El análisis de las relaciones entre parámetros muestra
correlaciones significativas entre los parámetros para todos los
casos excepto para IR y FD en G2, por lo que estos parámetros
proporcionan información complementaria, ya que analizan
aspectos diferentes de la señal como la morfología de las ondas
de activación y su frecuencia. La existencia de correlación entre
ambas para G1 puede ser debida a otras causas, tales como las
modificaciones en ambos factores inducidas por la presencia de
reentradas o colisiones entre frentes de activación..
Como conclusión, los resultados obtenidos sugieren que el
entrenamiento físico produce una respuesta cardíaca más
estable ante FV, debida a modificaciones intrínsecas en las
características electrofisiológicas cardíacas
Analysis of the influence of parasympathetic postganglionic neurons on cardiac response in ventricular fibrillation
Physical training modifies the sympathetic-vagal
balance of autonomic nervous system. Previous studies
have shown that such training also produces intrinsic
modifications of cardiac electrophysiological properties
in isolated heart during Ventricular Fibrillation (VF).
Ten NZW trained rabbits were studied to test if the
modifications are related to the activity of
postganglionic parasympathetic neurons. Two records
per subject were acquired during VF: before (G1) and
after (G2) the infusion of atropine to inhibit the activity
of neurons. Mapping records were obtained using a
240-channel electrode array located in the left ventricle
of isolated heart (perfused by Langendorff system). VF
was induced by stimulation at increasing frequencies.
To analyze the time course of fibrillation, the records
were processed in 4-second consecutive segments. For
each channel and segment, the following parameters
were computed: 1) Dominant Frequency (DF), obtained
by the Welch periodogram b) Normalized Energy (NE)
in a frequency band centered at the DF; c) Regularity
Index (RI), which analyzes the similarity of local
activation waves in every segment and channel; d)
Coefficients of Variance of DF (CVDF), NE (CVNE)
and RI (CVRI).
For each segment, we obtained the average value of
each of the parameters analyzed for all electrodes. The
results are: a) DF (G1: 13.671 ± 0.509 Hz, G2: 14.783
± 0.455 Hz), b) NE (G1: 0.398 ± 0.014; G2: 0.380 ±
0.013); c) RI (G1: 0.855 ± 0.017; G2: 0.865 ± 0.015), d)
CVDF (G1: 0.109 ± 0.009; G2: 0.098 ± 0.008), e)
CVNE (G1: 0.398 ± 0.014; G2: 0.380 ± 0.013 ) f) CVRI
(G1: 0.084 ± 0.009; G2: 0.078 ± 0.008).
None of these parameters showed significant
differences between groups. Thus, the parasympathetic
postganglionic neurons seem to have no effect on the
cardiac response in VF due to physical training