Modifications of long-term heart rate variability produced in an experimental model of diet-induced metabolic syndrome.

Metabolic syndrome (MetS) has been linked to a higher prevalence of cardiac arrhythmias, the most frequent being atrial fibrillation, but the mechanisms are not well understood. One possible underlying mechanism may be an abnormal modulation of autonomic nervous system activity, which can be quantified by analysing heart rate variability (HRV). Our aim was to investigate the modifications of long-term HRV in an experimental model of diet-induced MetS to identify the early changes in HRV and the link between autonomic dysregulation and MetS components. NZW rabbits were randomly assigned to control (n = 10) or MetS (n = 10) groups, fed 28 weeks with high-fat, high-sucrose diet. 24-hour recordings were used to analyse HRV at week 28 using time-domain, frequency-domain and nonlinear analyses. Time-domain analysis showed a decrease in RR interval and triangular index (Ti). In the frequency domain, we found a decrease in the low frequency band. Nonlinear analyses showed a decrease in DFA-α1 and DFA-α2 (detrended fluctuations analysis) and maximum multiscale entropy. The strongest association between HRV parameters and markers of MetS was found between Ti and mean arterial pressure, and Ti and left atrial diameter, which could point towards the initial changes induced by the autonomic imbalance in MetS.

Development and application to clinical practice of a validated HPLC method for the analysis of ß-glucocerebrosidase in Gaucher disease.

The main objective of our study is to develop a simple, fast and reliable method for measuring ß-glucocerebrosidase activity in Gaucher patients leukocytes in clinical practice. This measurement may be a useful marker to drive dose selection and early clinical decision making of enzyme replacement therapy. We measure the enzyme activity by high-performance liquid chromatography with ultraviolet detection and 4-nitrophenyl-ß-d-glucopyranoside as substrate. A cohort of eight Gaucher patients treated with enzyme replacement therapy and ten healthy controls were tested; median enzyme activity values was 20.57mU/ml (interquartile range 19.92-21.53mU/ml) in patients and mean was 24.73mU/ml (24.12-25.34mU/ml) in the reference group, which allowed the establishment of the normal range of ß-glucocerebrosidase activity. The proposed method for leukocytes glucocerebrosidase activity measuring is fast, easy to use, inexpensive and reliable. Furthermore, significant differences between both populations were observed (p=0.008). This suggests that discerning between patients and healthy individuals and providing an approach to enzyme dosage optimization is feasible. This method could be considered as a decision support tool for clinical monitoring. Our study is a first approach to in depth analysis of enzyme replacement therapy and optimization of dosing therapies.

Ventricular remodelling in rabbits with sustained high-fat diet.

AIM: Excess weight gain and obesity are one of the most serious health problems in the western societies. These conditions enhance risk of cardiac disease and have been linked with increased prevalence for cardiac arrhythmias and sudden death. Our goal was to study the ventricular remodelling occurring in rabbits fed with high-fat diet (HFD) and its potential arrhythmogenic mechanisms. METHODS: We used 15 NZW rabbits that were randomly assigned to a control (n = 7) or HFD group (n = 8) for 18 weeks. In vivo studies included blood glucose, electrocardiographic, and echocardiographic measurements. Optical mapping was performed in Langendorff-perfused isolated hearts. RESULTS: Body weight (3.69 ± 0.31 vs. 2.94 ± 0.18 kg, P < 0.001) and blood glucose levels (230 ± 61 vs. 141 ± 14 mg dL(-1) , P < 0.05) were higher in the HFD group vs. controls. The rate-corrected QT interval and its dispersion were increased in HFD rabbits vs. controls (169 ± 10 vs. 146 ± 13 ms and 37 ± 11 vs. 9 ± 2 ms, respectively; P < 0.05). Echocardiographic analysis showed morphological and functional alterations in HFD rabbits indicative of left ventricle (LV) hypertrophy. Isolated heart studies revealed no changes in repolarization and propagation properties under conditions of normal extracellular K(+) , suggesting that extrinsic factors could underlie those electrocardiographic modifications. There were no differences in the dynamics of ventricular fibrillation (frequency, wave breaks) in the presence of isoproterenol. However, HFD rabbits showed a small reduction in action potential duration and an increased incidence of arrhythmias during hyperkalaemia. CONCLUSION: High-fat feeding during 18 weeks in rabbits induced a type II diabetes phenotype, LV hypertrophy, abnormalities in repolarization and susceptibility to arrhythmias during hyperkalaemia.

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

AIM: Myocardial stretching is an arrhythmogenic factor. Optical techniques and mechanical uncouplers are used to study the mechanoelectric feedback. The aim of this study is to determine whether the mechanical uncouplers 2,3-butanedione monoxime and Blebbistatin hinder or modify the electrophysiological effects of acute mechanical stretch. METHODS: The ventricular fibrillation (VF) modifications induced by acute mechanical stretch were studied in 27 Langendorff-perfused rabbit hearts using epicardial multiple electrodes and mapping techniques under control conditions (n = 9) and during the perfusion of 2,3-butanedione monoxime (15 mM) (n = 9) or Blebbistatin (10 µm) (n = 9). RESULTS: In the control series, myocardial stretch increased the complexity of the activation maps and the dominant frequency (DF) of VF from 13.1 ± 2.0 Hz to 19.1 ± 3.1 Hz (P < 0.001, 46% increment). At baseline, the activation maps showed less complexity in both the 2,3-butanedione monoxime and Blebbistatin series, and the DF was lower in the 2,3-butanedione monoxime series (11.4 ± 1.2 Hz; P < 0.05). The accelerating effect of mechanical stretch was abolished under 2,3-butanedione monoxime (maximum DF = 11.7 ± 2.4 Hz, 5% increment, ns vs baseline, P < 0.0001 vs. control series) and reduced under Blebbistatin (maximum DF = 12.9 ± 0.7 Hz, 8% increment, P < 0.01 vs. baseline, P < 0.0001 vs. control series). The variations in complexity of the activation maps under stretch were not significant in the 2,3-butanedione monoxime series and were significantly attenuated under Blebbistatin. CONCLUSION: The accelerating effect and increased complexity of myocardial activation during VF induced by acute mechanical stretch are abolished under the action of 2,3-butanedione monoxime and reduced under the action of Blebbistatin.

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 a physical 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 different 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 fibrillation (VF), using a spectral method. The electrophysiological protocol was performed before and during continuous atropine administration (1 µM), 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 findings reveal that the myocardial electrophysiological modifications produced by physical training are not mediated by intrinsic cardiac parasympathetic activity.

[Study of prescriptions issued in base health areas of the Primary Care Administration of Sabadell]. / Estudio de la prescripción inducida de las áreas básicas de salud de la Dirección de Atención Primaria Sabadell.

OBJECTIVES: To quantify and describe Primary Care (PC) prescription originated by specialists, doctors outside the public health system and users. DESIGN: A descriptive, crossover study. SETTING: Eight base health areas in Primary Care, Sabadell, Barcelona. PATIENTS AND OTHER PARTICIPANTS: The medical prescriptions issued by 96 Primary Care doctors during a month. The information on the treatments begun during the study period were analysed. MEASUREMENTS AND MAIN RESULTS: 34,319 drugs products were prescribed for new conditions. 64.9% of these originated with the Primary Care doctor, 31.9% in specialist or private care, and 3.2% were requested by the user. The main diagnostic groups associated with prescriptions originating elsewhere were acute respiratory pathology, followed by Rheumatism not affecting the joints, anxiety and depression. CONCLUSIONS: In our milieu, a high percentage of prescriptions originate outside Primary Care. This study has identified the distribution of this prescription originating elsewhere and the variability, both in amount and origin, of PC prescriptions. It could also serve as a useful point of reference for other similar contexts.