Juan Guerrero

The influence of verapamil on serum digoxin concentration.

The-effect of verapamil on the pharmacokinetics of digoxin was studied in 49 patients with chronic atrial fibrillation. A dose of 240 mg/day of verapamil was given to the patients who were receiving a stable dose of digoxin. Serum digoxin levels rose from 0.76 ± 0.54 ng/ml (mean ± SD) to 1.31 ± 0.54 ng/ml during verapamil treatment (p < 0.0005). This effect was dose-dependent, as shown in seven subjects who received 160 mg and then, 240 mg of verapamil: There was a stepwise rise in serum digoxin concentration from a control value of 0.60 ± 0.11 ng/ml to 0.84 ± 0.18 ng/ml and 1.24 ± 0.40 ng/ml, respectively (p < 0.01 for both steps). The effect of verapamil developed gradually within the first few days in seven subjects in whom serum digoxin concentration reached, within 7 days, 90% of the increase observed 14 days after onset of verapamil. Renal digoxin clearance decreased significantly (26.1 ± 9.7 vs 55.1 ± 12.3 ml/min, p < 0.005) in six patients in whom serum digoxin concentration increased. It did not change in one patient in whom serum digoxin concentration was not influenced by verapamil. Creatinine clearance did not change in any of these seven. The same effects on digoxin clearance were observed in three normal subjects. Among the 49 patients, verapamil resulted in the development of signs and symptoms that suggested digitalis toxicity in seven. Verapamil significantly increases serum digoxin concentration. The process is dose-dependent and gradual, and it is at least partially explained by reduced renal excretion without reduction in glomerular filtration. The dose of digoxin may need readjustment in patients who are concomitantly receiving verapamil.

Alteration of Ventricular Fibrillation by Flecainide, Verapamil, and Sotalol An Experimental Study

BACKGROUND The purpose of this study was to determine whether the myocardial electrophysiological properties are useful for predicting changes in the ventricular fibrillatory pattern. METHODS AND RESULTS Thirty-two Langendorff-perfused rabbit hearts were used to record ventricular fibrillatory activity with an epicardial multiple electrode. Under control conditions and after flecainide, verapamil, or d,l-sotalol, the dominant frequency (FrD), type of activation maps, conduction velocity, functional refractory period, and wavelength (WL) of excitation were determined during ventricular fibrillation (VF). Flecainide (1.9+/-0.3 versus 2.4+/-0.6 cm, P<0. 05) and sotalol (2.1+/-0.3 versus 2.5+/-0.5 cm, P<0.05) prolonged WL and diminished FrD during VF, whereas verapamil (2.0+/-0.2 versus 1. 7+/-0.2 cm, P<0.001) shortened WL and increased FrD. Simple linear regression revealed an inverse relation between FrD and the functional refractory period (r=0.66, P<0.0001), a direct relation with respect to conduction velocity (r=0.33, P<0.01), and an inverse relation with respect to WL estimated during VF (r=0.49, P<0.0001). By stepwise multiple regression, the functional refractory periods were the only predictors of FrD. Flecainide and sotalol increased the circuit size of the reentrant activations, whereas verapamil decreased it. The 3 drugs significantly reduced the percentages of more complex activation maps during VF. CONCLUSIONS The activation frequency is inversely related to WL during VF, although a closer relation is observed with the functional refractory period. Despite the diverging effects of verapamil versus flecainide and sotalol on the activation frequency, WL, and size of the reentrant circuits, all 3 drugs reduce activation pattern complexity during VF.

The acute hemodynamic effects of intravenous verapamil in coronary artery disease. Assessment by equilibrium-gated radionuclide ventriculography.

The acute hemodynamic effects of an i.v. bolus of verapamil, 0.1 mg/kg or 0.06–0.075 mg/kg, were examined by serial radionuclide studies in 46 patients with coronary artery disease. In 20 patients with ejection fractions (EFs) > 35% (group 1A), verapamil, 0.1 mg/kg given over 1–1½ minutes, had a biphasic effect: first, a transient decrease in EF accompanied by increased left ventricular (LV) volumes and cardiac output equivalents; then, an overshoot of EF to values above control, accompanied by a decrease in peripheral vascular resistance and a drastic decrease in LV volumes, while cardiac output equivalent remained slightly elevated. In eight patients with EFs < 35% (group 1B), only the first effect on EF was noted. In 10 patients with EFs > 35% (group 2), verapamil, 0.06–0.075 mg/kg, exerted qualitatively similar but milder effects on hemodynamic function. Finally, verapamil, 0.1 mg/kg given more slowly, over 2–2½ minutes, produced no significant changes in EF or LV volumes in another eight patients (group 3). The acute effects of verapamil are thus both time-related and dose-dependent. They are also related to the baseline functional reserve of the left ventricle. This study documents that verapamil exerts a depressant effect on LV function. However, the transient nature of this depression and the quick recovery to normal or above-normal values indicate that verapamil, in the doses used in this study, is safe to use intravenously in patients with coronary artery disease.

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.

Quantification of the Modifications in the Dominant Frequency of Ventricular Fibrillation under Conditions of Ischemia and Reperfusion: An Experimental Study

The characteristics of ventricular fibrillatory signals vary as a function of the time elapsed from the onset of arrhythmia and the maneuvers used to maintain coronary perfusion. The dominant frequency (FrD) of the power spectrum of ventricular fibrillation (VF) is known to decrease after interrupting coronary perfusion, though the corresponding recovery process upon reestablishing coronary flow has not been quantified to date. With the aim of investigating the recovery of the FrD during reperfusion after a brief ischemic, period, 11 isolated and perfused rabbit heart preparations were used to analyze the signals obtained with three unipolar epicardial electrodes (E1‐E3) and a bipolar electrode immersed in the thermostatizfid organ bath (E4), following the electrical induction of VF. Recordings were made under conditions of maintained coronary perfusion (5 min), upon interrupting perfusion (15 mini, and after reperfusion (5 min), FrD was determined using Welchs method. The variations in FrD were quantified during both ischemia and reperfusion, based on an exponential model AFrD = A exp (‐t/C). During ischemia ΔFrD is the difference between FrD and the minimum value, while t is the time elapsed from the interruption of coronary perfusion. During reperfusion ΔFrD is the difference between the maximum value and FrD, while t is the time elapsed from the restoration of perfusion, A is one of the constants of the model, and C is the time constant. FrD exhibited respective initial values of 16.20 ± 1.67, 16.03 ± 1.38, and 16.03 ± 1.80 Hz in the epicardial leads, and 15.09 ±1.07 Hz in the bipolar lead within the bath. No significant variations were observed during maintained coronary perfusion. The fit of the FrD variations to the model during ischemia and reperfusion proved significant in nine experiments. The mean time constants C obtained on fitting to the model during ischemia were as follows: El =294.4 ± 75.6, E2 = 225.7 ± 48.5, E3 = 327.4 ± 79.7, and E4 = 298.7 ± 43.9 seconds. The mean values of C obtained during reperfusion, and the significance of the differences with respect to the ischemic period were: El = 57.5 ± 8.4 (P ± 0.01), E2 = 64.5 ± 11.2 (P0.01), E3 = 80.7 ± 13.3 (P < 0.01), and E4 = 74.9 ± 13.6 (P < 0.0001). The time course variations of the FrD of the VF power spectrum fit an exponential model during ischemia and reperfusion. The time constants of the model during reperfusion after a brief ischemic period are significantly shorter than those obtained during ischemia.

Opposite effects of myocardial stretch and verapamil on the complexity of the ventricular fibrillatory pattern: an experimental study.

CHORRO, F.J., et al.: Opposite Effects of Myocardial Stretch And Verapamil on The Complexity of The Ventricular Fibrillatory Pattern: An Experimental Study. An experimental model is used to analyze the effects of ventricular stretching and verapamil on the activation patterns during VF. Ten Langendorff‐perfused rabbit hearts were used to record VF activity with an epicardial multiple electrode before, during, and after stretching with an intraventricular balloon, under both control conditions and during verapamil (Vp) infusion (0.4–0.8 μmol). The analyzed parameters were dominant frequency (FrD) spectral analysis, the median (MN) of the VF intervals, and the type of activation maps during VF (I = one wavelet without block lines, II = two simultaneous wavelets with block lines, III = three or more wavelets with block lines). Stretch accelerates VF (FrD: 22.8 ± 6.4 vs 15.2 ± 1.0 Hz, P < 0.01; MN: 48 ± 13 vs 68 ± 6 ms, P < 0.01). On fitting the FrD time changes to an exponential model after applying and suppressing stretch, the time constants (stretch: 101.2 ± 19.6 s; stretch suppression: 97.8 ± 33.2 s) do not differ significantly. Stretching induces a significant variation in the complexity of the VF activation maps with type III increments and type I and II decrements (control: I = 17.5%, II = 50.5%, III = 32%; stretch: I = 7%, II = 36.5%, III = 56.5%, P < 0.001). Vp accelerates VF (FrD: 20.9 ± 1.9 Hz, P < 0.001 vs control; MN: 50 ± 5 ms, P < 0.001 vs control) and diminishes activation maps complexity (I = 25.5%, II = 60.5%, III = 14%, P < 0.001 vs control). On applying stretch during Vp perfusion, the fibrillatory process is not accelerated to any greater degree. However, type I and II map decrements and type III increments are recorded, though reaching percentages similar to control (I = 16.5%, II = 53%, III = 30.5%, NS vs control). The following conclusions were found: (1) myocardial stretching accelerates VF and increases the complexity of the VF activation pattern; (2) time changes in the FrD of VF during and upon suppressing stretch fit an exponential model with similar time constants; and (3) although stretching and verapamil accelerate the VF process, they exert opposite effects upon the complexity of the fibrillatory pattern.

Modifications in the Evolution of the Dominant Frequency in Ventricular Fibrillation Induced by Amiodarone, Diltiazem, and Flecainide An Experimental Study

In 22 anesthetized mongrel dogs, spectral methods were used to analyze the surface electrocardiogram (ECG) for the time course of the dominant frequency in ventricular fibrillation and its modifications under the influence of amiodarone, diltiazem, and flecainide. The ECG was recorded over 5 minutes after triggering ventricular fibrillation. Following A/D conversion and by applying the Fourier fast transform, the frequency spectrum of the signals was obtained. In group 1 (5 dogs), the ECGs were obtained without prior drug administration; group 2 (5 dogs) first received amiodarone, 5 mg/kg; group 3 (7 dogs) received diltiazem, 0.2 mg/kg; and group 4 (5 dogs) received flecainide, 2 mg/kg. All drugs were administered intravenously. An initial increase in the dominant frequency of ventricular fibrillation was found in the control group and also in the groups that received amiodarone, diltiazem, or flecainide. Diltiazem significantly increased the dominant frequency and diminished the arrhythmia-slowing process. Amiodarone and flecainide tended to diminish the dominant frequency.

BioLab: An Educational Tool for Signal Processing Training in Biomedical Engineering

This paper introduces and evaluates BioLab, a tool for teaching biosignal processing. BioLab has been used in the biomedical engineering module that is given in the second semester of the fifth year of the electronic engineering degree at the University of Valencia, Spain. This module and its correspondent curricular pathway are also reviewed. BioLab allows the results obtained with digital processing techniques to be shown interactively in the theory classes, and it also provides support in laboratory sessions. The graphic interface of BioLab simplifies its learning and use and provides access to processing and visualization functions by means of menus. The tool is based on Matlab since the students have had previous experience in this environment. BioLab also supports diverse formats of data files, which facilitate access to real records and their conversion to usable formats. The modular structure of BioLab allows it to be easily extended to other educational materials that are related to signal processing and to research applications. An evaluation of BioLab has revealed that students found it useful for understanding the general concepts of digital processing and biosignal processing in particular. The students also found BioLab very easy to learn and use

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.

Causal relationships between neurons of the nucleus incertus and the hippocampal theta activity in the rat

The nucleus incertus is a key node of the brainstem circuitry involved in hippocampal theta rhythmicity. Synchronisation exists between the nucleus incertus and hippocampal activities during theta periods. By the Granger causality analysis, we demonstrated a directional information flow between theta rhythmical neurons in the nucleus incertus and the hippocampus in theta‐on states. The electrical stimulation of the nucleus incertus is also able to evoke a phase reset of the hippocampal theta wave. Our data suggest that the nucleus incertus is a key node of theta generation and the modulation network.