The results strongly support the hypothesis that IK1 plays an important role in rotor stabilization and VF dynamics.

Background-Styryl voltage-sensitive dyes (e.g. di-4-ANEPPS) have been successfully used for optical mapping in cardiac cells and tissues. However, their utility for probing electrical activity deep inside the myocardial wall and in blood-perfused myocardium has been limited because of light scattering and high absorption by endogenous chromophores and hemoglobin at blue-green excitation wavelengths.

Abstract-The mechanisms by which Naϩ -channel blocking antiarrhythmic drugs terminate atrial fibrillation (AF) remain unclear. Classical "leading-circle" theory suggests that Na ϩ -channel blockade should, if anything, promote re-entry. We used an ionically-based mathematical model of vagotonic AF to evaluate the effects of applying pure Na ϩ -current (I Na ) inhibition during sustained arrhythmia. Under control conditions, AF was maintained by 1 or 2 dominant spiral waves, with fibrillatory propagation at critical levels of action potential duration (APD) dispersion. I Na inhibition terminated AF increasingly with increasing block, terminating all AF at 65% block. During 1:1 conduction, I Na inhibition reduced APD (by 13% at 4 Hz and 60% block), conduction velocity (by 37%), and re-entry wavelength (by 24%). During AF, I Na inhibition increased the size of primary rotors and reduced re-entry rate (eg, dominant frequency decreased by 33% at 60% I Na inhibition) while decreasing generation of secondary wavelets by wavebreak. Three mechanisms contributed to I Na block-induced AF termination in the model: (1) enlargement of the center of rotation beyond the capacity of the computational substrate; (2) decreased anchoring to functional obstacles, increasing meander and extinction at boundaries; and (3) reduction in the number of secondary wavelets that could provide new primary rotors. Optical mapping in isolated sheep hearts confirmed that tetrodotoxin dose-dependently terminates AF while producing effects qualitatively like those of I Na inhibition in the mathematical model. We conclude that pure I Na inhibition terminates AF, producing activation changes consistent with previous clinical and experimental observations. These results provide insights into previously enigmatic mechanisms of class I antiarrhythmic drug-induced AF termination. The full text of this article is available online at http://circres.ahajournals.org (Circ Res. 2005;96:e35-e47.) Key Words: atrial fibrillation Ⅲ mathematical model Ⅲ class I drugs Ⅲ sodium channels C lass I antiarrhythmic drugs terminate clinical atrial fibrillation (AF), but the electrophysiological mechanisms remain poorly understood. 1 AF is generally considered to be a re-entrant arrhythmia, and the stability of AF is classically related to the wavelength. 2 The wavelength (product of refractory period and conduction velocity [CV]) is thought to represent the minimum path length for re-entry and therefore to determine the size of functional re-entry circuits. 3 The most commonly accepted mechanism for antiarrhythmic drug termination of AF is drug-induced wavelength increases that reduce the number of circuits that the atria may accommodate.Experimental evidence has been presented suggesting that class I antiarrhythmic agents act on AF by changing the effective refractory period (ERP) and the wavelength. 2,4,5 Recent data have challenged established notions of antiarrhythmic drug action by showing that potent Na ϩ -channel blockers can terminate AF without increasing the wav...

A rapid impairment of myocardial impedance occurs after 30 minutes of coronary occlusion, and its onset is better defined by shift in phase angle than by rise in tissue resistivity. Phase 1b arrhythmias are associated with marked impedance changes, and both are delayed by preconditioning. Reversion of ST-segment elevation is partially associated with impairment of myocardial impedance, but other factors play a role as well.

The investigation of processes of ischemia in different organ tissues is very important for the development of methods of protection and preservation during surgical procedures. Electrical impedance spectroscopy was used to distinguish between different tissues and their degree of ischemia. We describe mathematical methods used to adjust experimental data to Cole-Cole models for one-circle and two-circle impedance loci and a study of the main parameters for representing the behavior of ischemia in time. In vivo and in situ postmortem measurements of different tissues from pigs are shown in the 100 Hz to 1 MHz range. The Cole parameters that best characterize the ischemia are R0 and fc.

Zaitsev AV. Three distinct phases of VF during global ischemia in the isolated blood-perfused pig heart. Am J Physiol Heart Circ Physiol 293: H1617-H1628, 2007. First published June 1, 2007; doi:10.1152/ajpheart.00130.2007.-Changes in ventricular fibrillation (VF) organization occurring after the onset of global ischemia are relevant to defibrillation and survival but remain poorly understood. We hypothesized that ischemia-specific dynamic instability of the action potential (AP) causes a loss of spatiotemporal periodicity of propagation and broadening of the electrocardiogram (ECG) frequency spectrum during VF in the ischemic myocardium. We recorded voltage-sensitive fluorescence of di-4-ANEPPS (anterior left ventricle, 35 ϫ 35 mm, 64 ϫ 64 pixels) and the volumeconducted ECG in six blood-perfused hearts during 10 min of VF and global ischemia. We used coefficient of variation (CV) to estimate variability of AP amplitude, AP duration, and diastolic interval (CV-APA, CV-APD, and CV-DI, respectively). We computed excitation median frequency (Median_F), spectral width of the AP and ECG (SpW-AP and SpW-ECG, respectively), wavebreak incidence (WBI), and recurrence of propagation direction (RPD). We found three distinct phases of local VF dynamics: "relatively periodic" (Յ1 min, high Median_F, moderate AP variability, high WBI, low RPD), "highly periodic" (1-2 min, reduced Median_F, low AP variability, low WBI, high RPD), and "aperiodic" (3-10 min, low Median_F, high AP variability, high WBI, low RPD). In one experiment, spontaneous conversion from the aperiodic to the highly periodic phase occurred after 5 min of ischemia. The SpW-ECG was correlated with SpW-AP, CV-APD, and CV-APA. We conclude that 1) at least three distinct phases of VF dynamics are present in our model, and 2) the newly described aperiodic phase is related to ischemia-specific dynamic instability of the AP shape, which underlies broadening of the ECG spectrum during VF evolution. ventricular fibrillation; action potential; electrocardiogram ONE IMPORTANT DECISION that an emergency care professional faces at the scene of cardiac arrest is whether to initiate cardiopulmonary resuscitation (CPR) before the application of a shock, or to defibrillate first. Population studies indicate that the "CPR first" strategy improves survival if the ventricular fibrillation (VF) duration exceeds 3-4 min ("circulatory phase") but not at the earlier "electrical" phase of VF (18). This observation motivated recent studies aimed at estimating VF duration based on the structure and spectral content of the electrocardiogram (ECG) waveform (6, 27, 34). Furthermore, various quantitative measures of "order" in the ECG waveform can predict the likelihood of rescue shock success, restoration of circulation, and survival to hospital discharge (4, 6). However, the relationship between the structure of the ECG waveform and the spatiotemporal dynamics of the fibrillatory waves in the myocardium remains unknown.VF organization evolves naturally after its onset as a result of glo...

The use of voltage-sensitive fluorescent dyes (VSD) for noninvasive measurement of the action potential (AP) in isolated cells has been hindered by low-photon yield of the preparation, dye toxicity, and photodynamic damage. Here we used a new red-shifted VSD, di-4-ANBDQBS, and a fast electron-multiplied charge-coupled device camera for optical AP (OAP) recording in guinea pig cardiac myocytes. Loading di-4-ANBDQBS did not alter APs recorded with micropipette. With short laser exposures (just enough to record one OAP every 1-5 min), di-4-ANBDQBS yielded fluorescent signals with very high signal-to-background ratios (change in fluorescence on depolarization/fluorescence at resting potential: 19.2 ± 4.1%) and signal-to-noise ratios (40 ± 13.2). Quantum chemical calculations comparing the ANBDQ chromophore to the conventional ANEP chromophore showed that the higher wavelength and the greater voltage sensitivity of the former have the same electro-optical origin: a longer path for electron redistribution in the excited state. OAP closely tracked simultaneously recorded electrical APs, permitting measurement of AP duration within 1% error. Prolonged laser exposure caused progressive AP duration prolongation and instability. However, these effects were alleviated or abolished by reducing the dye concentration and by perfusion with antioxidants. Thus the presented technique provides a unique opportunity for noninvasive AP recording in single cardiomyocytes.

Healed myocardial infarction has been recognized by its particular tissue electrical impedance spectrum measured with intramural needle electrodes in animal models. The aim of this study was to develop a percutaneous approach for in vivo recognition of areas of healed myocardial infarction by measuring myocardial electrical impedance with an intracavitary contact electrocatheter. Electrical impedance (resistance and phase angle) of normal myocardium and of a 2-month-old anterior transmural infarction were measured in nine chloralose anesthetized pigs by applying alternating currents from 1 kHz to 1 MHZ between a bipolar intracavitary catheter and a reference electrode placed on the epicardium (group I, n = 4) or on the precordium (group II, n = 5). Resistance of the infarcted myocardium was lower than that of healthy tissue at all current frequencies (ANOVA, P < 0.001) (i.e., at 1 kHz: 15 +/- 4 omega vs 50 +/- 19 omega in group I, and 64 +/- 13 omega vs 76 +/- 13 omega in group II). Phase angle at 316 kHz best differentiated transmural infarction from normal tissue (group I: -2.5 +/- 1.9 degrees vs -14.8 +/- 4.6 degrees, P < 0.001; group II: +0.7 +/- 1.0 degrees vs -2.7 +/- 1.4 degrees, P < 0.001). This study shows that analysis of myocardial impedance spectrum using a percutaneous intracavitary contact catheter approach permits on-line recognition of areas of healed transmural myocardial infarction. This technique may be useful to optimize clinical application of energy sources (i.e., radiofrequency ablation, laser myocardial revascularization).