Notizen: It is well known that the ability to fibrillate is intrinsic to a normal ventricle that exceeds a critical mass. The questions we address are how is ventricular fibrillation (VF) initiated and perpetuated in normal myocardium, and why is VF not seen more often in the general population if all ventricles have the ability to fibrillate. To study the mechanisms of VF, we used computerized mapping techniques with up to 512 channels of simultaneous multisite recordings for data acquisition. The data were then processed for dynamic display of the activation patterns and for mathematical analyses of the activation intervals. The results show that in normal ventricles, VF can be initiated by a single strong premature stimulus given during the vulnerable period of the cardiac cycle. The initial activations form a figure-eight pattern. Afterward, VF will perpetuate itself without any outside help. The self-perpetuation itself is due to at least two factors. One is that single wave fronts spontaneously break up into two or more wavelets. The second is that when two wavelets intersect perpendicular to each other, the second wavelet is broken by the residual refractoriness left over from the first wavelet. Mathematical analyses of the patterns of activation during VF revealed that VF is a form of chaos, and that transition from ventricular tachycardia (VT) to VF occurs via the quasiperiodic route. In separate experiments, we found that we can convert VF to VT by tissue size reduction. The physiological mechanism associated with the latter transition appears to be the reduction of the number of reentrant wave fronts and wandering wavelets. Based on these findings, we propose that the reentrant wave fronts and the wandering wavelets serve as the physiological equivalent of coupled oscillators. A minimal number of oscillators is needed for VF to perpetuate itself, and to generate chaotic dynamics; hence a critical mass is required to perpetuate VF. We conclude that VF in normal myocardium is a form of reentrant cardiac arrhythmia. A strong electrical stimulus initiates single or dual reentrant wave fronts that break up into multiple wavelets. Sometimes short-lived reentry is also generated during the course of VF. These organized reentrant and broken wavelets serve as coupled oscillators that perpetuate VF and maintain chaos. Although the ability to support these oscillators exists in a normal ventricle, the triggers required to generate them are nonexistent in the normal heart. Therefore, VF and sudden death do not happen to most people with normal ventricular myocardium. © 1998 American Institute of Physics.

Notizen: In support of the spiral wave theory of reentry, simulation studies and animal models have been utilized to show various patterns of spiral wave tip motion such as meandering and drifting. However, the demonstration of these or any other patterns in cardiac tissues have been limited. Whether such patterns of spiral tip motion are commonly observed in fibrillating cardiac tissues is unknown, and whether such patterns form the basis of ventricular tachycardia or fibrillation remain debatable. Using a computerized dynamic activation display, 108 episodes of atrial and ventricular tachycardia and fibrillation in isolated and intact canine cardiac tissues, as well as in vitro swine and myopathic human cardiac tissues, were analyzed for patterns of nonstationary, spiral wave tip motion. Among them, 46 episodes were from normal animal myocardium without pharmacological perturbations, 50 samples were from normal animal myocardium, either treated with drugs or had chemical ablation of the subendocardium, and 12 samples were from diseased human hearts. Among the total episodes, 11 of them had obvious nonstationary spiral tip motion with a life span of 〉2 cycles and with consecutive reentrant paths distinct from each other. Four patterns were observed: (1) meandering with an inward petal flower in 2; (2) meandering with outward petals in 5; (3) irregularly concentric in 3 (core moving about a common center); and (4) drift in 1 (linear core movement). The life span of a single nonstationary spiral wave lasted no more than 7 complete cycles with a mean of 4.6±4.3, and a median of 4.5 cycles in our samples. Conclusion: (1) Patently evident nonstationary spiral waves with long life spans were uncommon in our sample of mostly normal cardiac tissues, thus making a single meandering spiral wave an unlikely major mechanism of fibrillation in normal ventricular myocardium. (2) A tendency toward four patterns of nonstationary spiral tip motion was observed. © 1998 American Institute of Physics.

Notizen: Vulnerability to VF in Humans. Introduction: Shocks during the vulnerable period of the cardiac cycle induce ventricular fibrillation (VF) if their strength is above the VF threshold (VFT) and less than the upper limit of vulnerability (ULV). However, the range of shock strengths that constitutes the vulnerable zone and the corresponding range of coupling intervals have not been defined in humans. The ULV has been proposed as a measure of defibrillation because it correlates with the defibrillation threshold (DFT), but the optimal coupling interval for identifying it is unknown. Methods and Results: We studied 14 patients at implants of transvenous cardioverter defibrillators. The DFT was defined as the weakest shock that defibrillated after 10 seconds of VF. The ULV was defined as the weakest shock that did not induce VF when given at 0, 20, and 40 msec before the peak of the T wave or 20 msec after the peak in ventricular paced rhythm at a cycle length of 500 msec. The VFT was defined as the weakest shock that induced VF at any of the same four intervals. To identify the upper and lower boundaries of the vulnerable zone, we determined the shock strengths required to induce VF at all four intervals for weak shocks near the VFT and strong shocks near the ULV. The VFT was 72 ± 42 V, and the ULV was 411 ± 88 V. In all patients, a shock strength of 200 V exceeded the VFT and was less than the ULV. The coupling interval at the ULV was 19 ± 11 msec shorter than the coupling interval at the VFT (P 〈 0.001). The vulnerable zone showed a sharp peak at the ULV and a less distinct nadir at the VFT. A 20-msec error in the interval at which the ULV was measured could have resulted in underestimating it by a maximum of 95 ± 31 V. The weakest shock that did not induce VF was greater for the shortest interval tested than for the longest interval at both the upper boundary (356 ± 108 V vs 280 ± 78 V; P 〈 0.01) and lower boundary (136 ± 68 msec vs 100 ± 65 msec; P 〈 0.05). Conclusions: The human vulnerable zone is not symmetric with respect to a single coupling interval, but slants from the upper left to lower right. Small differences in the coupling interval at which the ULV is determined or use of the coupling interval at the VFT to determine the ULV may result in significant variations in its measured value. An efficient strategy for inducing VF would begin by delivering a 200-V shock at a coupling interval 10 msec before the peak of the T wave.

Notizen: DOSHI, R.N., et al.: Initial Experience with an Active-Fixation Defibrillation Electrode and the Presence of Nonphysiological Sensing. Nonphysiological sensing by a pacing and defibrillation electrode may result in inappropriate defibrillator discharges and/or inhibition of pacing. Active-fixation electrodes may be more likely to sense diaphragmatic myopotentials because of the protrusion of the screw for fixation. In addition, the movement of the fixation screw in an integrated bipolar lead system could also result in inappropriate sensing. This may be increasingly important in patients who are pacemaker dependent because the dynamic range of the autogain feature of these devices is much more narrow. Five of 15 consecutive patients who received a CPI model 0154 or 0155 active-fixation defibrillation electrode with an ICD system (CPI Ventak AV3DR model 1831 or CPI Ventak VR model 1774 defibrillator) are described. In 2 of the 15 patients, nonphysiological sensing appearing to be diaphragmatic myopotentials resulted in inappropriate defibrillator discharges. Both patients were pacemaker dependent. Changes in the sensitivity from nominal to less sensitive prevented inappropriate discharges. In one patient, discreet nonphysiological sensed events with the electrogram suggestive of ventricular activation was noted at the time of implantation. This was completely eliminated by redeployment of the active-fixation lead in the interventricular septum. In two other patients, discreet nonphysiological sensed events resulted in intermittent inhibition of ventricular pacing after implantation. These were still seen in the least sensitive autogain mode for ventricular amplitude. These were not seen on subsequent interrogation 1 month after implantation. Increased awareness of nonphysiological sensing is recommended. The CPI 0154 and 0155 leads seem to be particularly prone to this abnormality. Particular attention should be made when deploying an active-fixation screw for an integrated bipolar lead. This increased awareness is more important when a given individual is pacemaker dependent, which may warrant DFT testing in a least or less sensitive mode in these patients.

Notizen: The chaos theory is based on the idea that phenomena that appear disordered and random may actually be produced by relatively simple deterministic mechanisms. The disordered (aperiodic) activation that characterizes a chaotic motion is reached through one of a few well-defined paths that are characteristic of nonlinear dynamical systems. Our group has been studying VF using computerized mapping techniques. We found that in electrically induced VF, reentrant wavefronts (spiral waves) are present both in the initial tachysystolic stage (resembling VT) and the later tremulous incoordination stage (true VF). The electrophysiological characteristics associated with the transition from VT to VF is compatible with the quasiperiodic route to chaos as described in the Ruelle-Takens theorem. We propose that specific restitution of action potential duration (APD) and conduction velocity properties can cause a spiral wave (the primary oscillator) to develop additional oscillatory modes that lead to spiral meander and breakup. When spiral waves begin to meander and are modulated by other oscillatory processes, the periodic activity is replaced by unstable quasiperiodic oscillation, which then undergoes transition to chaos, signaling the onset of VF. We conclude that VF is a form of deterministic chaos. The development of VF is compatible with quasiperiodic transition to chaos. These results indicate that both the prediction and the control of fibrillation are possible based on the chaos theory and with the advent of chaos control algorithms.

Notizen: Transmembrane action potentials (TAPs) were recorded during simultaneous mapping of a reentrant wavefront induced in canine isolated atria. The activation pattern was visualized dynamically using a high resolution electrode catheter mapping system. During functional reentry (spiral wave), cells in the core of the spiral wave remained quiescent near their resting membrane potential. Cells away from the core progressively gained TAP amplitude and duration, and at the periphery of the spiral wave the cells generated TAPs with full height and duration. During anatomical reentry, when the tip of the wavefront remained attached to the obstacle (a condition of high source-to-sink ratio), the TAP near the obstacle had normal amplitude and duration. However, when the tip of the wavefront detached from the obstacle (condition of lowered source-to-sink ratio) the TAP lost amplitude and duration. These results are consistent with the theory that the source-to-sink ratio determines the safety factor for wave propagation and wave block near the core. With decreasing source-to-sink ratio, TAP progressively decreases in amplitude and duration. In the center of the core, the cells, while excitable, remain quiescent near their resting potential. This decrease reflects a progressive decrease in the source-to-sink ratio. TAP vanishes in the core where cells remain quiescent near their resting potential. Functional and meandering reentrant wavefronts are compatible with the spiral mechanism of reentry where block at the rotating point is provided by the steep curvature of the wave tip.

Notizen: The authors hypothesized that rapid electrical stimulation can induce nerve sprouting in canine atria, and that LA pacing is more effective than RA pacing in inducing sustained AF. Chronic rapid (20 Hz) LA epicardial pacing was performed in six dogs. Sustained AF (〉48 hours) was induced within 23 ± 8 days, which was much faster than that with RA endocardial pacing using the same protocol (139 ± 84 days, P 〈 0.05). Nerves were identified by immunocytochemical techniques. In all dogs, growth-associated protein 43-positive (sprouting) nerve density was highest near the pacing site, and the rapid LA pacing resulted in differential nerve sprouting among the LA, left superior pulmonary vein (LSPV), interatrial septum (IAS), and RA (5521 ± 1496, 3154 ± 2355, 3953 ± 1164, 1559 ± 1077 μm2/mm2, respectively, P = 0.0032). Tyrosine hydroxylase-positive (sympathetic) nerve density were not significantly different among groups (2726 ± 1165, 1586 ± 558, 2156 ± 1741, 1509 ± 1242 μm2/mm2, respectively). The nerves were inhomogeneously distributed. LA epicardial pacing induced sustained AF much faster than RA endocardial pacing and rapid electrical stimulation can induce inhomogeneous nerve sprouting near the pacing site. (PACE 2003; 26:2247–2252)

Notizen: Mechanisms of Deflbhllation. The aim of this article is to review the current concepts of ventricular defibrillation. We studied the interaction between strong electrical stimulas and cardiac responses in both animal models and in humans. We found that a premature stimulus (S2) of appropriate strength results in figure-eight reentry in vitro by inducing propagated graded responses. The same stimulation protocol induces figure-eight reentry and ventricular fibrillation (VF) in vivo. When the S2 strength and the magnitude of graded responses increase beyond a critical level, the increase in refractoriness at the site of the stimulus becomes so long that the unidirectional block becomes bidirectional block, preventing the formation of reentry (upper limit of vulnerability [DLV]). In other studies, we found that the effects of an electrical stimulation on reentry is in part determined by the timing of the stimulus. A protective zone is present after the induction of VF and after an unsuccessful defibrillation shock during which an electrical stimulus can terminate reentry and protect the heart from VF. These results indicate that the effects of a defibrillation shock is dependent on both the strength and the timing of the shock. Timing is not important in areas where the shock field strength is 〈 ULV because the shock terminates all reentry hut cannot reinitiate new ones. However, in areas where shock field strength is 〈 ULV, the effects of the shock are determined by the timing of the shock relative to local VF activations. This ULV hypothesis of defibrillation explains the probablistic nature of ventricular defibrillation. It also indicates that, to achieve a high probability of successful defibrillation, a shock must result in a shock field strength of 〈 ULV throughout the ventricles.

Notizen: Vulnerability in Ventricular Fibrillation. Introduction: It was postulated that a subthreshold defibrillation shock failed to halt ventricular fibrillation because the shock itself reinitiated Ventricular fibrillation by falling into the vulnerable period of the wave fronts. Whether or not the timing of the vulnerable period is determined by the ventricular fibrillation cycle length is unknown. Methods and Results: We determined the patterns of epicardial activation in ten dogs by computerized mapping techniques during unsuccessful defibrillation. Lidocaine was then given to prolong the ventricular fibrillation cycle length, and the computerized mapping studies were repeated. The results showed that lidocaine increased the ventricular fibrillation cycle length from 110 ± 13 msec to 156 ± 5 msec (P 〈 (0.001). Among 55 episodes of unsuccessful defibrillation, the site of the earliest postshock activation occurred in the center of the mapped tissue 12 times at baseline and 14 times during lidocaine infusion. At electrodes that registered as post-shock early sites, the preshock intervals clustered within a narrow range both before (58 ± 14 msec) and during (10l ± 18 msec, P 〈 0.001) lidocaine infusion. The correlation between the preshock intervals and the ventricular fibrillation cycle length was significant for these 26 sites (r = 0.87, P〈 0.001.). Conclusion: We conclude that a vulnerable period is present during ventricular fibrillation, and the timing of the vulnerable period is determined by the ventricular fibrillation cycle length.