Effect of global ischemia and reperfusion during ventricular fibrillation in myopathic human hearts.

The effect of lack of global coronary perfusion on myocardial activation rate, wavebreak, and its temporal progression during human ventricular fibrillation (VF) is not known. We tested the hypothesis that global myocardial ischemia decreases activation rate and spatiotemporal organization during VF in myopathic human hearts, while increasing wavebreak, and that a short duration of reperfusion can restore these spatiotemporal changes to baseline levels. The electrograms were acquired during VF in a human Langendorff model using global mapping consisting of two 112-electrode arrays placed on the epicardium and endocardium simultaneously. We found that global myocardial ischemia results in slowing of the global activation rate (combined endo and epi), from 4.89+/-0.04 Hz. to 3.60+/-0.04 Hz. during the 200 s of global ischemia (no coronary flow) (P<0.01) in eight myopathic hearts. Two minutes of reperfusion contributed to reversal of the slowing with activation rate value increasing close to VF onset (4.72+/-0.04 Hz). In addition, during the period of ischemia, an activation rate gradient between the endocardium (3.76+/-0.06 Hz) and epicardium (3.45+/-0.06 Hz) was observed (P<0.01). There was a concomitant difference in wavebreak index (that provides a normalized parameterization of phase singularities) between the epicardium (11.29+/-2.7) and endocardium (3.25+/-2.7) during the 200 s of ischemia (P=0.02). The activation rate, gradient, and wavebreak changes were reversed by short duration (2 min) of reperfusion. Global myocardial ischemia of 3 min leads to complex spatiotemporal changes during VF in myopathic human hearts; these changes can be reversed by a short duration of reperfusion.

Spatiotemporal frequency analysis of ventricular fibrillation in explanted human hearts.

Ventricular fibrillation (VF) is a medical condition that occurs due to rapid and irregular electrical activity of heart. If undiagnosed or untreated, VF leads to sudden cardiac death. VF has been studied by researchers for over 100 years to elucidate the mechanism that maintains VF, and thus to arrive at therapeutic options. VF is a nonstationary process, and it manifests into variations in the waveform morphology, phase, and frequency dynamics of the surface electrograms. Dominant frequency analysis (DF maps) and phase maps are two widely used complementary approaches in assessing the evolution of VF process. These techniques are applied to electrograms or fluorescence signals obtained with voltage-sensitive dyes. In spite of VF being a nonstationary process, most of the existing literature limits frequency analysis to a segmented, time-averaged spectral analysis, where valuable information on the instantaneous temporal evolution of the spectral characteristics is lost. In order to resolve this issue, in this paper, we present a joint time-frequency approach that is suited for VF analysis and demonstrate the application of instantaneous mean frequency (IMF) in interpreting VF episodes. Human VF sources are rarely anatomically stable and are migratory. Traditional DF techniques fail in tracking this migratory behavior. IMF, on the other hand, can deal with these migratory sources and conduction blocks better than DF approaches. Results of the analysis using the electrograms of 204 VF segments obtained from 13 isolated human hearts (explanted during cardiac transplantation) indicate that in 81% of the VF segments, there were significant changes in the spatiotemporal evolution of the frequency, suggesting that IMF provides better mechanistic insight of these signals. The IMF tool presented in this paper demonstrates potential for applications in tracking frequency patterns, conduction blocks, and arriving at newer therapies to modulate VF.

Electrogram fractionation in murine HL-1 atrial monolayer model.

BACKGROUND: Complex fractionated atrial electrograms have been suggested as important targets for catheter ablation of atrial fibrillation. The etiology and the mechanism of these signals have not been completely elucidated because of limitations of interpretation of these signals in relation to simultaneously acquired signals in the neighboring atrial tissue. OBJECTIVE: This study sought to study the origin of electrogram fractionation under the conditions of rotor formation and wave fragmentation, using atrial monolayer preparations. METHODS: We performed optical mapping of 45 atrial monolayer preparations using a complementary metal oxide semiconductor (CMOS) Brainvision Ultima camera system (SciMedia-Brainvision, Tokyo, Japan). RESULTS: We observed stable rotors in 32 of the 45 recordings. The derived bipolar electrograms did not show complex fractionation at the core of the rotor in any of the 32 recordings. We were also able to show that 2 bipolar electrodes placed adjacent to the core of a stable rotor in a zone where there is no wave break will record electrical activity for the majority of the rotor's cycle length. In 13 of the 45 recordings, wave break or wave collision events were present. Of these, 8 of 13 recordings showed complex fractionation. In 19 of the 27, simulation of meandering rotors also showed complex fractionation. CONCLUSION: Complex fractionated electrograms can be recorded at sites of migrating rotors and wave break. No fractionation occurs at the core of a stable rotor. Electrograms that span the rotor cycle length and alternate between 2 bipoles that straddle the core can identify site of a stable rotor.

Cardiac stimulation with high voltage discharge from stun guns.

The ability of an electrical discharge to stimulate the heart depends on the duration of the pulse, the voltage and the current density that reaches the heart. Stun guns deliver very short electrical pulses with minimal amount of current at high voltages. We discuss external stimulation of the heart by high voltage discharges and review studies that have evaluated the potential of stun guns to stimulate cardiac muscle. Despite theoretical analyses and animal studies which suggest that stun guns cannot and do not affect the heart, 3 independent investigators have shown cardiac stimulation by stun guns. Additional research studies involving people are needed to resolve the conflicting theoretical and experimental findings and to aid in the design of stun guns that are unable to stimulate the heart.

Optical mapping of Langendorff-perfused human hearts: establishing a model for the study of ventricular fibrillation in humans.

Our objective was to establish a novel model for the study of ventricular fibrillation (VF) in humans. We adopted the established techniques of optical mapping to human ventricles for the first time to determine whether human VF is the result of wave breaks and singularity point formation and is maintained by high-frequency rotors and fibrillatory conduction. We describe the technique of acquiring optical signals in human hearts during VF, their characteristics, and the feasibility of possible analyses that could be performed to elucidate mechanisms of human VF. We used explanted hearts from five cardiomyopathic patients who underwent transplantation. The hearts were Langendorff perfused with Tyrode solution (95% O(2)-5% CO(2)), and the potentiometric dye di-4-ANEPPS was injected as a bolus into the coronary circulation. Fluorescence was excited at 531 +/- 20 nm with a 150-W halogen light source; the emission signal was long-pass filtered at 610 nm and recorded with a mapping camera. Fractional change of fluorescence varied between 2% and 12%. Average signal-to-noise ratio was 40 dB. The mean velocity of VF wave fronts was 0.25 +/- 0.04 m/s. Submillimetric spatial resolution (0.65-0.85 mm), activation mapping, and transformation of the data to phase-based analysis revealed reentrant, colliding, and fractionating wave fronts in human VF. On many occasions the VF wave fronts were as large as the entire vertical length (8 cm) of the mapping field, suggesting that there are a limited number of wave fronts on the human heart during VF. Phase transformation of the optical signals allowed the first demonstration ever of phase singularity point, wave breaks, and rotor formation in human VF. This method provides opportunities for potential analyses toward elucidation of the mechanisms of VF and defibrillation in humans.

Wave similarity of human ventricular fibrillation from bipolar electrograms.

AIMS: The aim of this report was to review existing techniques for assessment of directionality in fibrillation and to describe the concept of wave similarity analysis in human VF. METHODS: We applied a technique called wave similarity analysis to bipolar electrograms to study directionality during various rhythms (sinus rhythm, ventricular tachycardia and ventricular fibrillation) in humans. This technique uses the barycentre to determine the activation time and a similarity index is calculated using a technique described previously for AF studies. RESULTS: We show here that using the wave similarity concept it is possible to recognize myocardial regions that are activated from multiple directions and differentiate those areas from regions that are activated by wave fronts in similar direction or at the exact mirror angle in ventricular fibrillation. CONCLUSIONS: Wave similarity analysis provides a tool for assessing directional organization in human VF. This analysis of directional organization may have implications for the study of mechanisms of VF in the clinical arena.

Ventricular fibrillation in myopathic human hearts: mechanistic insights from in vivo global endocardial and epicardial mapping.

Ventricular fibrillation (VF) is an important cause of sudden cardiac death and cardiovascular mortality in patients with cardiomyopathy. Although it was generally believed that chaotic reentrant wavefronts underlie VF in humans, there is emerging evidence of spatiotemporal organization during early VF. The mechanism of this organization of electrical activity in early VF is unknown in myopathic hearts. We studied early VF in vivo, intraoperatively in five cardiomyopathic patients. Simultaneous electrograms were obtained from the epicardium and endocardium in left ventricular cardiomyopathy and from the endocardium in right ventricular myopathy. The Hilbert transform was used to derive the phase of the electrograms. Rotors were identified by isolating phase singularity points. Rotors were present in all of the myopathic hearts studied during VF and cumulatively lasted a mean of 3.2 +/- 2.0 s of the 7.0 +/- 4.0 s of the VF segments analyzed. For each surface mapped, 3.6 +/- 2.9 rotors were identified for the duration mapped. The average number of cycles completed by these rotors was 4.9 +/- 4.9. The longest rotor lasted 10.2 +/- 6.2 rotations and lasted 2.0 +/- 1.2 s. The rotors on the endocardium had a cycle length of 192 +/- 33 ms compared with 220 +/- 15 ms on the epicardium (P=0.08). There is centrifugal activation of electrical activity from these rotors, and they give rise to domains that activate at faster rates with evidence of conduction block at the border with slower domains. These rotors frequently localized to border regions of myocardium with bipolar electrogram amplitude of <0.5 mV. The organization of electrical activity during early VF in myopathic human hearts is characterized by wavefronts emanating from a few rotors.

Cardiac electrophysiological consequences of neuromuscular incapacitating device discharges.

OBJECTIVES: The purpose of this study was to evaluate the cardiac consequences of neuromuscular incapacitating device (NID)/stun gun discharge in an experimental model. BACKGROUND: The large-voltage electrical discharges from NIDs have been suggested to pose a risk for triggering cardiac arrhythmias. METHODS: Intracardiac catheters and blood pressure transducers were inserted before the application of NID discharges in six anesthetized pigs. Two different commercially available models (NID-1 and NID-2), two different vectors of discharges (thoracic: parallel to the long axis of the heart on the chest wall, and nonthoracic: away from the chest, across the abdomen), and two different durations of discharge (5 and 15 s) were tested. The effect of simulated adrenergic stress using epinephrine was also evaluated. RESULTS: We studied a total of 150 discharges to 6 pigs; 74 of these discharges resulted in stimulation of the myocardium, as documented by electrical capture (mean ventricular rate during stimulation and capture, 324 +/- 66 beats/min). Of the 94 thoracic discharges, 74 stimulated the myocardium, compared with none from 56 nonthoracic discharges (p < 0.0001). During 16 discharges with epinephrine, there were 13 episodes of stimulation of the myocardium, of which 1 induced ventricular fibrillation and 1 caused ventricular tachycardia. Thoracic discharges from NID-1 were more likely to stimulate the myocardium than those from NID-2 (98% vs. 54%, p = 0.0007). CONCLUSIONS: In an experimental model, NID discharges across the chest can produce cardiac stimulation at high rates. This study suggests that NIDs may have cardiac risks that require further investigation in humans.