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 Ϯ 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 Ϯ 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.

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Background: Low-voltage–guided substrate modification is an emerging strategy in atrial fibrillation (AF) ablation. A major limitation to contemporary bipolar electrogram (EGM) analysis in AF is the resultant lower peak-to-peak voltage (V pp ) from variations in wavefront direction relative to electrode orientation and from fractionation and collision events. We aim to compare bipole V pp with novel omnipolar peak-to-peak voltages (V max ) in sinus rhythm (SR) and AF. Methods and Results: A high-density fixed multielectrode plaque was placed on the epicardial surface of the left atrium in dogs. Horizontal and vertical orientation bipolar EGMs, followed by omnipolar EGMs, were obtained and compared in both SR and AF. Bipole orientation has significant impact on bipolar EGM voltages obtained during SR and AF. In SR, vertical values were on average 66±119% larger than horizontal ( P =0.004). In AF, vertical values were on average 31±96% larger than horizontal ( P =0.07). Omnipole V max values were 99.9±125% larger than both horizontal (99.9±125%; P <0.001) and vertical (41±78%; P <0.0001) in SR and larger than both horizontal (76±109%; P <0.001) and vertical (52±70%; P value <0.0001) in AF. Vector field analysis of AF wavefronts demonstrates that omnipolar EGMs can account for collision and fractionation and record EGM voltages unaffected by these events. Conclusions: Omnipolar EGMs can extract maximal voltages from AF signals which are not influenced by directional factors, collision or fractionation, compared with contemporary bipolar techniques.

BackgroundCharacterization of myocardial health by bipolar electrograms are critical for ventricular tachycardia therapy. Dependence of bipolar electrograms on electrode orientation may reduce reliability of voltage assessment along the plane of arrhythmic myocardial substrate. Hence, we sought to evaluate voltage assessment from orientation‐independent omnipolar electrograms.Methods and ResultsWe mapped the ventricular epicardium of 5 isolated hearts from each species—healthy rabbits, healthy pigs, and diseased humans—under paced conditions. We derived bipolar electrograms and voltage peak‐to‐peak (Vpps) along 2 bipolar electrode orientations (horizontal and vertical). We derived omnipolar electrograms and Vpps using omnipolar electrogram methodology. Voltage maps were created for both bipoles and omnipole. Electrode orientation affects the bipolar voltage map with an average absolute difference between horizontal and vertical of 0.25±0.18 mV in humans. Vpps provide larger absolute values than horizontal and vertical bipolar Vpps by 1.6 and 1.4 mV, respectively, in humans. Bipolar electrograms with the largest Vpps from either along horizontal or vertical orientation are highly correlated with omnipolar electrograms and with Vpps values (0.97±0.08 and 0.94±0.08, respectively). Vpps values are more consistent than bipoles, in both beat‐by‐beat (CoV, 0.28±0.19 versus 0.08±0.13 in human hearts) and rhythm changes (0.55±0.21 versus 0.40±0.20 in porcine hearts).ConclusionsOmnipoles provide physiologically relevant and consistent voltages that are along the maximal bipolar direction on the plane of the myocardium.

LDVF in human hearts is characterized by focal endocardial activity with mid-myocardial wave break and not by re-entry. This arrhythmia is modulated by rapid activations in early VF that lead to spontaneous Purkinje fiber activity.

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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.

Vasodepressor reactions were induced in 27 rats by a combination of inferior vena caval occlusion and an infusion of isoproterenol. A vasodepressor reaction was defined as paradoxical heart rate slowing during inferior vena caval occlusion. The R-R intervals were measured at 5-s intervals before, during, and after 60 s of inferior vena caval occlusion. The purpose of this study was to examine the role of the right and left vagus nerve and the right and left stellate ganglia in this reflex. Under control conditions inferior vena caval occlusion accelerated the rate (R-R, -15.9 +/- 0.9 ms). During an infusion of isoproterenol (0.5-1.0 micrograms.min-1), inferior vena caval occlusion produced paradoxical rate slowing, i.e., a vasodepressor reaction (R-R, +75.0 +/- 2.2 ms). The vasodepressor reaction was examined during inferior vena caval occlusion and isoproterenol under the following additional states: atropine methyl bromide or right vagotomy did not alter the reaction; left vagotomy eliminated the reaction; and right or left stellectomy greatly reduced the vasodepressor reaction. We conclude the following: (1) left vagal afferents mediate the vasodepressor reaction; (2) cardiac sympathetic fibers participate in the vasodepressor reaction by withdrawing efferent tone through the right stellate ganglion, and by generating the afferent signal, which triggers the vasodepressor reaction through the left stellate ganglion.