Heart Rate Variability as Biomarker for Prognostic of Metabolic Disease

Lifestyle emerging diseases like obesity, metabolic syndrome (MeS), and diabetes mellitus are considered high-risk factors for lethal arrhythmias and side effects. A Poincaré plot is constructed with the time series of RR and PP electrocardiogram (ECG) intervals, using two stages: the new phase and the old phase. We proposed this diagram of two dimensions, a way to quantify and observe the regularity of events in space and time. Therefore, the heart rate variability (HRV) can be used as a biomarker for early prognostic and diagnostic of several metabolic diseases; additionally, this biomarker is obtained by a noninvasive tool like the electrocardiogram

Metabolic syndrome remodels electrical activity of the sinoatrial node and produces arrhythmias in rats

"In the last ten years, the incidences of metabolic syndrome and supraventricular arrhythmias have greatly increased. The metabolic syndrome is a cluster of alterations, which include obesity, hypertension, hypertriglyceridemia, glucose intolerance and insulin resistance, that increase the risk of developing, among others, atrial and nodal arrhythmias. The aim of this study is to demonstrate that metabolic syndrome induces electrical remodeling of the sinus node and produces arrhythmias. We induced metabolic syndrome in 2-month-old male Wistar rats by administering 20% sucrose in the drinking water. Eight weeks later, the rats were anesthetized and the electrocardiogram was recorded, revealing the presence of arrhythmias only in treated rats. Using conventional microelectrode and voltage clamp techniques, we analyzed the electrical activity of the sinoatrial node. We observed that in the sinoatrial node of “metabolic syndrome rats”, compared to controls, the spontaneous firing of all cells decreased, while the slope of the diastolic depolarization increased only in latent pacemaker cells. Accordingly, the pacemaker currents If and Ist increased. Furthermore, histological analysis showed a large amount of fat surrounding nodal cardiomyocytes and a rise in the sympathetic innervation. Finally, Poincaré plot denoted irregularity in the R-R and P-P ECG intervals, in agreement with the variability of nodal firing potential recorded in metabolic syndrome rats"

Multiple effects of 4-aminopyridine on feline and rabbit sinoatrial node myocytes and multicellular preparations

"4-aminopyridine (4-AP) is commonly used to block the transient outward potassium current, I(to), in cardiac and noncardiac tissues. In the present work, we found that 4-AP inhibited the rapid component of the delayed rectifier potassium current, I(Kr), in rabbit-isolated sinoatrial node myocytes by 25% (1 mM) and 51% (5 mM) and inhibited the slow component of the delayed rectifier potassium current, I(Ks), in cat- isolated sinoatrial node myocytes by 39% (1 mM) and 62% (5 mM). In cat- and rabbit-isolated sinoatrial node myocytes, 4-AP activated muscarinic receptors in a voltage-dependent manner to increase the acetylcholine-activated potassium current, I(KACh). In multicellular preparations of the central region of the sinoatrial node from nonreserpinized rabbits, 4-AP produced an increase in action potential overshoot, frequency, and rate of diastolic depolarization. In the presence of the beta-adrenergic antagonist propranolol, 4-AP produced a marked increase in duration and a marked decrease in maximum diastolic potential and eventually, cessation of the spontaneous activity in preparations from the sinoatrial central region. In multicellular preparations from reserpinized rabbits, 4-AP produced similar effects to those observed in the presence of propranolol. We conclude that 4-AP inhibits multiple cardiac K(+) currents, including I(to), I(Kr), and I(Ks), and that these activities mask I(KACh) activation"

Seguimiento farmacoterapéutico de antiparasitarios para pacientes pediátricos de Santa María Acuexcomac-México

"El Método Dáder para el seguimiento farmacoterapéutico ha sido una herramienta que permite detectar y solucionar problemas relacionados con la medicación y puede adaptarse a las condiciones de la población mexicana que vive en comunidades rurales. El programa se ofreció a 300 infantes de la comunidad de Santa María Acuexcomac, de los cuales solo 102 aceptaron participar. En la primera etapa se diagnosticaron 62 casos de parasitosis causada por Entamoeba histolytica, Himenolepis nana y/o Giardia lamblia. Se prescribieron quinfamida para los casos de amibiasis, albendazol para himenolepiasis y giardiasis, o ambos medicamentos para amibiasis en conjunción con himenolepiasis y/o giardiasis. Al finalizar esta etapa la adherencia al tratamiento farmacoterapeutico de los pacientes que se les realizo el seguimiento farmacoterapéutico fue en promedio de 96.9%, mientras que 76 % de estos pacientes no presentaron parasitosis en un segundo análisis coproparasitoscópico. En la segunda etapa se administró metronidazol para el tratamiento de amibiasis y/o giardiasis, y prazicuantel para el tratamiento de himenolepiasis. A todos los pacientes se les realizó el seguimiento farmacoterapéutico obteniéndose una adherencia del 81.8%. Al finalizar el programa ninguno de los pacientes a los cuales se les brindo el seguimiento farmacoterapéutico, presentaron parasitosis"

Ventricular dysfunction in obese and nonobese rats with metabolic syndrome

"Obesity and dyslipidemias are both signs of metabolic syndrome, usually associated with ventricular arrhythmias. Here, we tried to identify cardiac electrical alteration and biomarkers in nonobese rats with metabolic syndrome (MetS), and these findings might lead to more lethal arrhythmias than obese animals. The MetS model was developed in Wistar rats with high-sucrose diet (20%), and after twenty-eight weeks were obtained two subgroups: obese (OMetS) and nonobese (NOMetS). The electrocardiogram was used to measure the ventricular arrhythmias and changes in the heart rate variability. Also, we measured ventricular hypertrophy and its relationship with electrical activity alterations of both ventricles, using micro-electrode and voltage clamp techniques. Also, we observed alterations in the contraction force of ventricles where a transducer was used to record mechanical and electrical papillary muscle, simultaneously. Despite both subgroups presenting long QT syndrome (0.66 ± 0.05 and 0.66 ± 0.07 ms with respect to the control 0.55 ± 0.1 ms), the changes in the heart rate variability were present only in OMetS, while the NOMetS subgroup presented changes in QT interval variability (NOMetS SD = 1.8, SD2 = 2.8; SD1/SD2 = 0.75)"

Enhancement of early warning properties in the Kuramoto model and in an atrial fibrillation model due to an external perturbation of the system

"When a complex dynamical system is externally disturbed, the statistical moments of signals associated to it can be affected in ways that depend on the nature and amplitude of the perturbation. In systems that exhibit phase transitions, the statistical moments can be used as Early Warnings (EW) of the transition. A natural question is thus to wonder what effect external disturbances have on the EWs of system. In this work we study the impact of external noise added to the system on the EWs, with particular focus on understanding the importance of the amplitude and complexity of the noise. We do this by analyzing the EWs of two computational models related to biology: the Kuramoto model, which is a paradigm of synchronization for biological systems, and a cellular automaton model of cardiac dynamics which has been used as a model for atrial fibrillation. For each model we first characterize the EWs. Then, we introduce external noise of varying intensity and nature to observe what effect this has on the EWs. In both cases we find that the introduction of noise amplified the EWs, with more complex noise having a greater effect"

MeS increased risk of suffering arrhythmias.

<p>(<b>A</b>) Upper trace, representative electrocardiogram (ECG) of control rats. Lower trace; rats with MeS presented irregular sinusal rhythm (see asterisks). (<b>B</b>) Poincaré plot of ECG R-R interval evidenced an increase in the heart rate variability in MeS (n = 7; black) vs. control animals (n = 8; grey). The line dot represents the length and width of the area surrounding the points in Poincaré plot. (This plot was built with each interval R-R of ECG as a function of the previous R-R interval).</p

MeS increases adipose tissue and sympathetic innervation in sinoatrial node.

<p>(<b>A</b>) Immunofluorescence for tyrosine hydroxylase (TH) evidenced the sympathetic innervation of SA node. (<b>C</b>) In the same way, red oil staining showed adipose tissue surrounding nodal cardiomyocytes (arrows). (<b>B</b>) Quantification of stained areas revealed a major innervation and (<b>D</b>) a net increase of adipose tissue in SA nodes coming from rats with MeS (white arrows). Con: Control (n = 6); MES: MeS (n = 6).* p≤0.05 vs. control.</p

MeS remodels the electrical activity of sinoatrial node.

<p>(<b>A</b>) MeS decreases firing rate of true and latent pacemaker cells, (<b>B</b>) without any change in their location. (<b>C</b>). Note that true pacemaker cells in rats with MeS fire AP at higher frequencies than latent cells. § p≤0.05 vs. control.</p