More than 100 years ago, strong electric shocks were shown to terminate ventricular fibrillation (VF). Electrical defibrillation has been used clinically as the principal effective treatment for VF for more than half a century. Implantable cardioverter defibrillators capable of detecting and terminating VF are commonly used in patients at high risk for sudden cardiac death, and the prevalence of automatic external defibrillators has enhanced the availability of life-saving defibrillation therapy to a greater population. Despite increased accessibility to technology to deliver defibrillation shocks, t
More than 100 years ago, strong electric shocks were shown to terminate ventricular fibrillation (VF). Electrical defibrillation has been used clinically as the principal effective treatment for VF for more than half a century. Implantable cardioverter defibrillators capable of detecting and terminating VF are commonly used in patients at high risk for sudden cardiac death, and the prevalence of automatic external defibrillators has enhanced the availability of life-saving defibrillation therapy to a greater population. Despite increased accessibility to technology to deliver defibrillation shocks, the mechanisms by which shocks terminate VF are still not fully understood.
Global Mechanism of defibrillation
Computer simulations and experimental observations with catheter electrodes in close contact with cardiac tissue showed that areas close to shocking electrodes produce virtual electrodes that either hyperpolarize or depolarize the surrounding tissue. Monophasic shocks may be strong enough to terminate the wavefronts of VF, but fail to defibrillate because the shocks create virtual electrodes, which generate new wavefronts that reinitiate VF. The collagenous septae do not extend all the way to the epicardium. After the shock, an activation front arises near the boundary of the virtual cathode and spreads rapidly through the hyperpolarized tissue in the virtual anode, and a reentrant circuit is formed that causes the shock to fail.
Electrical shocks delivered during a critical repolarization portion of the cardiac cycle termed the vulnerable period can lead to VF. More than 100 years ago, it was observed that there is an upper limit of stimulus strength above which VF will not be induced, also known as the upper limit of vulnerability (ULV). Subsequent experiments demonstrated that the ULV and the defibrillation threshold (DFT) are closely related and that many of the mechanisms responsible for the initiation of VF by a shock in the vulnerable period are also active during defibrillation shocks. These considerations led to the ULV hypothesis, which states that for a shock to successfully terminate VF, it must alter the transmembrane potential throughout the myocardium in such a way that the wavefronts of VF are halted, yet new wavefronts that can reinitiate VF are not induced. These realizations led to the development of the critical point theory of defibrillation, which suggested that reentry was initiated at the intersection of critical points of local field strength and tissue with critical levels of recovery.
The important variable in the other type of critical point is the pattern of the virtual electrodes of hyperpolarization and depolarization caused by the shock, not the strength of the shock ∇V or the degree of refractoriness as in the first type of critical point. Within the hyperpolarized region, even though it is in phase 2 of the action potential and so is in its absolute refractory period, the myocardium is “deexcited” so that its action potential is truncated and excitability is restored. This restoration of excitability allows the adjacent depolarized region to activate the hyperpolarized tissue, giving rise to an activation front that forms a rotor around a critical point formed where the adjacent hyperpolarization and depolarization decrease to the point that a postshock activation front is not initiated. Thus, although the virtual electrodes are necessary to halt the fibrillatory activation fronts present at the time of the shock, the activation front formed in the deexcited region after the shock can lead to the reinitiation of reentry and the failure of the shock to defibrillate. Efimov and coworkers proposed that a biphasic waveform is better able to defibrillate because the second phase of the shock restores the ΔVm back toward the transmembrane potential levels before the shock, thus obliterating the virtual electrodes and preventing the launch of an activation front after the shock in the hyperpolarized region.
In summary, critical points are formed by a combination of the field gradients and the underlying refractoriness of the tissue. Reentry and refibrillation may occur at sites far from electrodes if the appropriate conditions are met.
Although the earliest activation appears almost immediately after the shock for the two types of critical points, the first postshock focus is not observed by epicardial electrical or optical mapping techniques for approximately 50 to 90 ms after the shock. To eliminate the possibility that intramural reentry or activation could be occurring during this epicardial isoelectric window, transmural activation was mapped following near-DFT strength shocks. Transmural mapping confirmed that there was a period of 58 ± 23 ms (mean ± standard deviation) before the first postshock activation and that these activations proceeded from a focus. It is possible that this focus arose either from a propagated graded response or from triggered activity. Because of the long interval from the shock until the first focal activity is observed, it has been hypothesized that this triggered activity is a delayed afterdepolarization. However, a study using pinacidil (early afterdepolarization inhibitor) and flunarizine (delayed afterdepolarization inhibitor) showed no significant change in DFT, isoelectric window, or first activation location. Also, some data suggest that these delayed foci arise from a slow propagated graded response. However, if these foci do arise from a delayed afterdepolarization, then the mechanism by which a biphasic waveform has a lower DFT than a monophasic waveform may be that it causes less postshock action potential prolongation, because an increased action potential duration increases the likelihood of delayed afterdepolarizations.
Questions remain regarding the source of the first postshock activation and the isoelectric window. There is also disagreement in the literature as to whether debrillation shocks themselves damage the heart. There are limited studies that investigate the mechanisms of defibrillation following long-duration VF, and there may be significant changes in the mechanisms of VF during the global ischemia in long-duration VF.
Time preceding a defibrillation shock is one of the greatest determinants of patient outcome. The probability of survival from an episode of VF decreases by approximately 10% per minute, with few patients surviving episodes of VF that last more than 10 min. Consequently, minimizing time to defibrillation through community awareness and access to defibrillators will likely lead to increased survival in VF patients.
Optical and electrical mapping techniques have improved our understanding of the cellular, tissue, and whole-organ mechanisms responsible for defibrillation. Shocks induce a change in transmembrane potential in myocytes that leads to termination of VF wavefronts. Microscopic tissue-level discontinuities such as myocyte bundles, collagenous septae, and blood vessels create secondary sources that allow shocks to activate cardiac tissue distant from the electrodes. Critical points of shock strength and recovering tissue created by shocks and critical points of virtual electrodes may determine if and how shocks cause new activation fronts that reinitiate VF.