© 2000 American Heart Association, Inc.
Editorials |
Fibrillating Myocardium
Rabbit Warren or Beehive?
From the Departments of Biomedical Engineering and Medicine, University of Alabama at Birmingham.
Correspondence to Jack M. Rogers, 1670 University Blvd, Volker Hall, B140, Birmingham, AL 35294. E-mail jmr{at}crml.uab.edu
Key Words: fibrillation • Fourier analysis • reentry • mapping
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Introduction |
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 Top Introduction References |
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Until 20 years ago, it was thought that atrial and ventricular fibrillation were highly disorganized, with tens or hundreds of tiny wandering wavelets simultaneously present and following ever-changing pathways.1 In this model, the disorganization is due to intrinsic heterogeneity of refractory periods that causes transitory islets of refractoriness about which wavelets circulate.
However, about two decades ago, a new view emerged. This model was based on the theoretical2 3 4 5 and experimental6 finding that the heart could support electrical waves that rotate about a functional, rather than anatomical, obstacle. These so-called rotors were thought to be the primary "organizing centers" for fibrillation, and refractory period heterogeneity was a secondary factor, possibly modulating and masking the activity of rotors, but not driving the rhythm.7
Indeed, electrical and optical mapping have demonstrated a considerable organization during ventricular fibrillation (VF).8 9 10 11 12 13 These studies indicate that activation fronts are frequently large during fibrillation and follow pathways that are centimeters in length. In addition, many of these activation fronts follow similar pathways. Surprisingly, however, after the first few seconds of VF, rotors are rarely observed. In several recent mapping studies, only 2% to 8% of activation fronts were identified as parts of reentrant circuits.13 14 15 In addition, most of the reentrant circuits were short-lived, lasting typically only slightly more than one cycle.
Consistent with these findings, many recently proposed mechanisms for fibrillation have focused on rotors as transient, unstable objects, and VF is explained in terms of how rotors break up to form the turbulent state seen in epicardial maps. In essence, "mother rotors" break up into "daughter rotors," which in turn break up in a continual chain of succession, as rabbits breeding in a warren. Individual rotors may or may not complete a full cycle of reentry. One proposed breakup mechanism is often called the restitution hypothesis and states that when the slope of the action potential duration (APD) restitution curve is greater than 1, then APD along reentrant wavefronts will undergo beat-to-beat oscillations, culminating in localized block and fractionation of the reentrant circuit.16 17 Another mechanism for rotor proliferation that can occur only in 3D tissue involves the interaction of reentrant wavefronts with boundaries. In 2D, the phase singularity at the center of a rotor is a point. In 3D, this point generalizes to a line, or filament, which can snake through the heart wall in a complex way.7 If the filament accumulates sufficient curvature, an isolated length may be annihilated at a boundary, cutting the filament in two. Theoretical studies have suggested several mechanisms by which filament curvature might arise.18 19 20
The recent work from Jalife and colleagues13 21 suggests that this recent emphasis on the breakup of rotors as the driving force for VF is misplaced. In this issue of Circulation Research, Zaitsev et al21 report that the activation rate does not change smoothly and continuously across the endocardial and epicardial surfaces of a slab of ventricular myocardium. Rather, the activation rate is constant over discrete regions called domains, which average 1.1 cm2 in area. Where two domains abut, activation fronts in the faster-activating domain enter the slower-activating domain with some of the activation fronts blocking at the boundary between domains in a Wenckebach-like pattern. Thus, the fastest domain appears to be driving the slower domains and to be the source for the arrhythmogenic mechanism that is responsible for the maintenance of the arrhythmia.
Zaitsev et al21 propose that the high-frequency source is a stable rotor, thus reviving the importance of the rotor as the organizing center for VF, with fibrillatory conduction away from the rotor playing a secondary role in the arrhythmia. In this study, as in previous mapping studies, sustained reentry was uncommonly observed, even in the fastest-activating domain. Instead, activation fronts were observed frequently to break through to the epicardial and endocardial surfaces, as has been observed by others.12 The authors propose that stable rotors are not evident because they are transmurally oriented and are therefore not visible on the epicardium. In simulation studies, this same group has shown that 3D reentrant circuits tend to orient themselves so that the filament of the reentrant core is parallel to the long axis of the myofibers.22 Given that the long axis of the ventricular myocardial fibers is primarily parallel to the epicardial and endocardial surfaces,23 this finding predicts that reentry should be primarily intramural, giving rise to breakthrough patterns on the epicardium and endocardium, as observed experimentally. Thus, according to this model of VF, the heart is a hive, not a warren, and the stable rotor serves as the queen in her hidden chamber, spawning wavefronts that do the work of fibrillation, but are not responsible for the perpetuation of the rhythm.
The hypothesis that VF is driven by stable, hidden rotors will require confirmation by transmural recordings. In principle, such recordings can be obtained using plunge-needle electrodes,24 optical sensors mounted on plunge needles,25 or transillumination techniques in which variations in light transmittance through a slab of tissue due to electrical activity are measured.26 Ideally, these data will be acquired from intact large-heart preparations that are not affected by confounding factors such as small myocardial mass, artificial slab boundaries, or electromechanical uncoupling agents.
Distinguishing between the VF mechanism proposed by Jalife and colleagues13 21 and alternative mechanisms may have important implications for future VF therapy. For example, it has been suggested that if VF is governed by rate-dependent APD oscillations (the restitution hypothesis), then VF may be controlled by drugs that flatten the slope of the restitution curve.16 In contrast, if stable reentry is most important, then completely different types of control strategy may be appropriate, for example, ablation or pace-termination of the reentrant site. This also raises the question whether VF would be terminated if the "queen rotor" were halted, or if it would quickly be replaced by the promotion of a new queen. Addressing these and other questions is sure to be a fertile and exciting area of research in the coming years.
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Footnotes |
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The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
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References |
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