Electrophysiological mechanisms of atrial flutter

Atrial flutter (AFL) is a common arrhythmia in clinical practice. Several experimental models such as tricuspid regurgitation model, tricuspid ring model, sterile pericarditis model and atrial crush injury model have provided important information about reentrant circuit and can test the effect of antiarrhythmic drugs. Human atrial flutter has typical and atypical forms. Typical atrial flutter rotates around tricuspid annulus and uses the crista terminalis and sometimes sinus venosa as the boundary. The IVC-tricuspid isthmus is a slow conduction zone and the target of radiofrequency ablation. Atypical atrial flutter may arise from the right or left atrium. Right atrial flutter includes upper loop reentry, free wall reentry and figure of eight reentry. Left atrial flutter includes mitral annular atrial flutter, pulmonary vein-related atrial flutter and left septal atrial flutter. Radiofrequency ablation of the isthmus between the boundaries can eliminate these arrhythmias.     

Effect of myocardial infarction and ischemia on induction of cardiac reentries and ventricular fibrillation

The present work is aimed at investigating the effects of myocardial infarction and ischemia on induction of ventricular fibrillation. Electrophysiologic effects of global and local ischemia (variation of the dispersion of refractory periods as well as conduction velocity) on initiation of reentry mechanisms was studied by means of computer simulations based on a cellular automata model of propagation of activation wave through a ventricular surface element. A local area of ischemia where effects of the dispersion of refractory periods are investigated is then simulated. This is made using a Gaussian distribution characterized by its mean and standard deviation. These simulations show that ischemia is capable of initiating reentry phenomena which propagate through the whole ventricle; they are responsible for ventricular fibrillation which causes sudden cardiac death, even when ischemia only involves limited parts of the myocardium. Statistical study of the probability of reentries as a function of both of the size of ischemic zones and the rate of dispersion of refractory periods shows that the latter parameter is of primary importance in triggering cardiac reentries.     

Electrophysiological investigation of the texture discrimination mechanisms

In electrophysiological and psychophysical experiments, we investigated mechanisms of the visual system underlying local and global texture processing. Textures included rectangular matrixes composed of Gabor patches (sine wave grating windowed by a Gaussian envelope). Orientation of each grating varied from 0 to 165 degrees with the step of 15 degrees. Matrixes differed by the amount of Gabor patches with vertical or horizontal orientation. The observers' task was to discriminate the dominant orientation. The advantage of such stimuli involved a possibility to calculate global statistics of the textures, which we considered as the difference between whole amount of vertical and horizontal orientations in the stimulus irrespective of their location. The local statistics was calculated as relative amount of spatially organized nearby gratings (i. e. collinear contours). The subjects' accuracy was low in discriminating less organized textures and gradually improved with the amount of vertically of horizontally oriented Gabor patches, while the reaction time decreased. Visual evoked potentials (VEPs) recorded from occipital lobes revealed different dependencies of their components' magnitude on the amount of equally oriented gratings. Amplitude of the late positive component P3 with latency 400 ms directly depended on the texture discriminability, and N2 wave with latency 180 ms had an S-like dependence. Opposite to that, the magnitude of P2 wave with latency 260 ms was maximal in response to less organized textures and gradually decreased with the amount of equally oriented gratings. The dependencies received were compared with the textures' statistics. Data analysis allowed us to suppose that, in the conditions of our experimental paradigm, two mechanisms were involved in discrimination of the textures--the local and the global processing. We believe that by recording VEPs one can separately investigate activity of these two processes.     

Computer modeling of ventricular fibrillation

Electrical activity of a heart in ventricular fibrillation was modeled as a sum of independent pulse streams with various amplitude-frequency and phase characteristics. Results of computer experiments were compared with those of real physiological experiments on rabbits. Identification of the model was carried out by means of the least-squares procedure. The offered technique allows a computer model investigation of internal structure of irregularities of ventricular fibrillation.     

Computer modeling of ventricular fibrillation

Electrical activity of a heart in ventricular fibrillation was modeled as a sum of independent pulse streams with various amplitude-frequency and phase characteristics. Results of computer experiments were compared with those of real physiological experiments on rabbits. Identification of the model was carried out by means of the least-squares procedure. The offered technique allows a computer model investigation of internal structure of irregularities of ventricular fibrillation.     

Electrophysiological response of rat ventricular myocytes to acidosis

The effects of acidosis on the action potential, resting potential, L-type Ca(2+) (I(Ca)), inward rectifier potassium (I(K1)), delayed rectifier potassium (I(K)), steady-state (I(SS)), and inwardly rectifying chloride (I(Cl,ir)) currents of rat subepicardial (Epi) and subendocardial (Endo) ventricular myocytes were investigated using the patch-clamp technique. Action potential duration was shorter in Epi than in Endo cells. Acidosis (extracellular pH decreased from 7.4 to 6.5) depolarized the resting membrane potential and prolonged the time for 50% repolarization of the action potential in Epi and Endo cells, although the prolongation was larger in Endo cells. At control pH, I(Ca), I(K1), and I(SS) were not significantly different in Epi and Endo cells, but I(K) was larger in Epi cells. Acidosis did not alter I(Ca), I(K1), or I(K) but decreased I(SS); this decrease was larger in Endo cells. It is suggested that the acidosis-induced decrease in I(SS) underlies the prolongation of the action potential. I(Cl,ir) at control pH was Cd(2+) sensitive but 4,4'-disothiocyanato-stilbene-2,2'-disulfonic acid resistant. Acidosis increased I(Cl,ir); it is suggested that the acidosis-induced increase in I(Cl,ir) underlies the depolarization of the resting membrane potential.     

Electrophysiological mechanisms of ventricular arrhythmias in relation to Andersen-Tawil syndrome under conditions of reduced IK1: a simulation study

Patients with Andersen-Tawil syndrome (ATS) mostly have mutations on the KCNJ2 gene, producing loss of function or dominant-negative suppression of the inward rectifier K(+) channel Kir2.1. However, clinical manifestations of ATS including dysmorphic features, periodic paralysis (hypo-, hyper-, or normokalemic), long QT, and ventricular arrhythmias (VAs) are considerably variable. Using a modified dynamic Luo-Rudy simulation model of cardiac ventricular myocytes, we attempted to elucidate mechanisms of VA in ATS by analyzing effects of the inward rectifier K(+) channel current (I(K1)) on the action potential (AP). During pacing at 1.0 Hz with extracellular K(+) concentration ([K(+)](o)) at 4.5 mM, a stepwise 10% reduction of Kir2.1 channel conductance progressively prolonged the terminal repolarization phase of the AP along with gradual depolarization of the resting membrane potential (RMP). At 90% reduction, early afterdepolarizations (EADs) became inducible and RMP was depolarized to -52.0 mV (control: -89.8 mV), followed by emergence of spontaneous APs. Both EADs and spontaneous APs were facilitated by a decrease in [K(+)](o) and suppressed by an increase in [K(+)](o). Simulated beta-adrenergic stimulation enhanced delayed afterdepolarizations (DADs) and could also facilitate EADs as well as spontaneous APs in the setting of low [K(+)](o) and reduced Kir2.1 channel conductance. In conclusion, the spectrum of VAs in ATS may include 1) triggered activity mediated by EADs and/or DADs and 2) abnormal automaticity manifested as spontaneous APs. These VAs can be aggravated by a decrease in [K(+)](o) and beta-adrenergic stimulation and may potentially induce torsade de pointes and cause sudden death. In patients with ATS, the hypokalemic form of periodic paralysis should have the highest propensity to VAs, especially during physical activity.     

Intracellular Ca dynamics in ventricular fibrillation

In the heart, membrane voltage (Vm) and intracellular Ca (Cai) are bidirectionally coupled, so that ionic membrane currents regulate Cai cycling and Cai affects ionic currents regulating action potential duration (APD). Although Cai reliably and consistently tracks Vm at normal heart rates, it is possible that at very rapid rates, sarcoplasmic reticulum Cai cycling may exhibit intrinsic dynamics. Non-voltage-gated Cai release might cause local alternations in APD and refractoriness that influence wavebreak during ventricular fibrillation (VF). In this study, we tested this hypothesis by examining the extent to which Cai is associated with Vm during VF. Cai transients were mapped optically in isolated arterially perfused swine right ventricles using the fluorescent dye rhod 2 AM while intracellular membrane potential was simultaneously recorded either locally with a microelectrode (5 preparations) or globally with the voltage-sensitive dye RH-237 (5 preparations). Mutual information (MI) is a quantitative statistical measure of the extent to which knowledge of one variable (Vm) predicts the value of a second variable (Cai). MI was high during pacing and ventricular tachycardia (VT; 1.13 +/- 0.21 and 1.69 +/- 0.18, respectively) but fell dramatically during VF (0.28 +/- 0.06, P < 0.001). Cai at sites 4-6 mm apart also showed decreased MI during VF (0.63 +/- 0.13) compared with pacing (1.59 +/- 0.34, P < 0.001) or VT (2.05 +/- 0.67, P < 0.001). Spatially, Cai waves usually bore no relationship to membrane depolarization waves during nonreentrant fractionated waves typical of VF, whereas they tracked each other closely during pacing and VT. The dominant frequencies of Vm and Cai signals analyzed by fast Fourier transform were similar during VT but differed significantly during VF. Cai is closely associated with Vm closely during pacing and VT but not during VF. These findings suggest that during VF, non-voltage-gated Cai release events occur and may influence wavebreak by altering Vm and APD locally.     

乳酸左氧氟沙星对豚鼠心肌细胞电生理的影响

目的了解乳酸左氧氟沙星(LVFX)对豚鼠心室肌细胞电生理的影响.方法经腹腔注射不同剂量的LVFX,记录并分析注药后5～360 min豚鼠Ⅱ导联心电图的QT间期,以及校正的QT间期(QTc).采用全细胞膜片钳技术,记录不同浓度LVFX对体外单个心室肌细胞的延迟整流钾电流(IK)的作用.结果①LVFX给药量为200 mg/kg时,心电图QT间期延长19.38%±3.15%(P＜0.05);在50 mg/kg和100 mg/kg等较低剂量时,QT间期延长不明显(P＞0.05).②LVFX抑制IK电流,且抑制作用呈现电压依赖性和浓度依赖性.结论LVFX可能通过抑制心肌细胞IK电流引起心脏QT间期延长,临床应谨慎使用.     

Electrophysiological characterization of left ventricular myocytes from obese Sprague-Dawley rat

Objective: Obesity is a complex multifactorial disease that is often associated with cardiac arrhythmias. Various animal models have been used extensively to study the effects of obesity on physiological functions, but, to our knowledge, no study related to ionic membrane currents has been performed on isolated cardiac myocytes. Therefore, we examined the electrophysiological characteristics of four ionic currents from isolated left ventricular myocytes of a high‐energy (HE)‐induced obesity rat model. Research Methods and Procedures: Male Sprague‐Dawley rats were fed with either a control diet or a diet containing 33% kcal as fat (HE) for 14 weeks starting at 6 weeks of age. Voltage‐clamp experiments were performed on ventricular myocytes. Leptin receptor (ObR) expression was measured using ObR enzyme‐linked immunosorbent assay. Results: In the HE group, rats designated as obese did not develop a cardiac hypertrophy, either at the organ level or at the cellular level. Densities and kinetics of the L‐type calcium current, the transient outward potassium current, the delayed rectifier potassium current, and the sodium‐calcium exchange current (I_NCX) were not significantly different between control and obese rats. A down‐regulation of ObR expression was evidenced in the heart of obese rats compared with controls. Acute exposure (5 minutes) of leptin (100 nM) did not induce a significant modification in the current densities either in control or in obese rats, except for I_NCX density measured in control rats. Discussion: The absence of effect of leptin on I_NCX in obese rats could be a potential arrhythmogenic substrate in obesity.