Electrophysiological effects of monophasic and biphasic stimuli in normal and infarcted dogs.

Though some biphasic waveforms significantly decrease the energy required for defibrillation, little is known about the effect of biphasic stimulation on the determination of other electrophysiological parameters in normal and infarcted hearts. To evaluate this, nine normal dogs and 12 dogs with myocardial infarction had activation threshold (AT), effective refractory period (ERP), strength-interval curves, and ventricular fibrillation threshold (VFT) determined with constant current stimulation to a pair of right ventricular plunge electrodes, and upper limit of vulnerability (ULV) and defibrillation threshold (DFT) determined with truncated exponential shocks delivered to a pair of wire electrodes coiled to contour the right and left ventricular epicardium. Each electrophysiological parameter was determined with a 5.5 msec monophasic and 5.5-msec biphasic (3.5 msec first phase) waveform. Though AT and VFT were not significantly different for the two waveforms, the ERP was significantly longer, the strength-interval curve shifted rightward, and the threshold for repetitive responses higher for biphasic stimuli. Compared to the monophasic waveform, the ULV and DFT were significantly decreased in a parallel fashion for the biphasic waveform. Neither the presence nor size of myocardial infarction significantly affected any of the measured electrophysiological parameters. In six additional dogs, sigmoid defibrillation probability curves were constructed from biphasic shocks of four energies including that of the DFT and ULV. The ULV energy predicted an effective dose that defibrillated 97% of the time (range 90%-100%). In conclusion, the increased defibrillation efficacy of the biphasic waveform is independent of its ability to activate fully repolarized myocardium and cannot be explained by a greater ability of biphasic waveforms to activate partially depolarized tissue. The parallel decrease in the ULV and DFT for biphasic stimulation and the finding that the ULV energy defibrillates with a high probability of success suggest similar underlying mechanisms for the ULV and defibrillation.

Influence of shock strength and timing on induction of ventricular arrhythmias in dogs.

We delivered strong shocks via electrodes on the left ventricular apex and the right atrium in seven dogs during the T wave of atrial pacing while recordings were made from 56 epicardial electrodes. After shocks that induced arrhythmias were given, the earliest activation occurred in the middle of the ventricles for lower-energy shocks and in the base for higher-energy shocks. For shocks late in the vulnerable period, activation was recorded soon after the shock, whereas for shocks early in the vulnerable period activation was not recorded for a mean of 70 ms (+/- 17 ms SD) after the shock. We also gave 1-J shocks during right and left ventricular pacing. For shocks early in the vulnerable period, activation initiating fibrillation arose in a focal pattern from the paced region. For shocks during the midportion of the vulnerable period, fibrillation arose by two leading circle reentrant loops rotating in opposite directions, one on the left and the other on the right ventricle. For shocks at the end of the vulnerable period, the two reentrant loops fused on the side of the heart opposite the pacing site to again form a single focal activation pattern. Thus the initial activation patterns of arrhythmias initiated by shocks, the time from the shock until earliest postshock activation, and the site of earliest postshock activation are strongly influenced by the coupling interval and strength of the shock.

Epicardial activation after unsuccessful defibrillation shocks in dogs.

To study defibrillation, shocks were given to seven dogs during electrically induced fibrillation, while recordings were made from 56 epicardial electrodes. Shocks were given via electrodes on the left ventricular apex and the right atrium, creating an uneven shock field with much higher potential gradients in the apex than in the base of the ventricles. For unsuccessful 0.01- to 0.05-J shocks, activation occurred soon after the shock at many sites in both the base and the apex. For 0.1- to 0.5-J shocks, the number of early activation sites was greatly decreased, and the latency from the shock until earliest recorded activation was greatly increased at the apex but not at the base. For 1- to 5-J shocks, one to three early sites were present and confined to the base, with a long latency between the shock and the appearance of these early sites. The latency and location of earliest activation were similar to those after 1- to 5-J shocks given to induce fibrillation during normal paced rhythm. Shocks of 10 J successfully defibrillated. These findings suggest that the shock field can have at least three effects. One, a weak field fails to halt the activation fronts of fibrillation. Two, a stronger field halts but then reinduces fibrillation in a manner similar to that of the same strength field during the vulnerable period of normal rhythm. Three, a still higher field halts fibrillation without reinitiating it. Successful defibrillation requires a shock strong enough to create this third field intensity throughout the ventricles.

Extracellular field required for excitation in three-dimensional anisotropic canine myocardium.

It is not known how well potential gradient, current density, and energy correlate with excitation by extracellular stimulation in the in situ heart. Additionally, the influence of fiber orientation and stimulus polarity on the extracellular thresholds for stimulation expressed in terms of these factors has not been assessed. To answer these questions for myocardium in electrical diastole, extracellular excitation thresholds were determined from measurements of stimulus potentials and activation patterns recorded from 120 transmural electrodes in a 35 X 20 X 5-mm region of the right ventricular outflow tract in six open-chest dogs. Extracellular potential gradients, current densities, energies, and their components longitudinal and transverse to the local fiber orientation at each recording site were calculated from the stimulus potentials produced by 3-msec constant-current stimuli. The resulting values in regions directly excited by the stimulus field were compared with the values in regions not directly excited but activated by the spread of wavefronts conducting away from the directly excited region. Magnitudes of 3.66 mA/cm2 for current density, 9.7 microJ/cm3 for energy, and 804 mV/cm for potential gradient yielded minimum misclassifications of 8%, 13%, and 17%, respectively, of sites directly and not directly excited. A linear bivariate combination of the longitudinal (l) and transverse (t) components of the potential gradient yielded 7% misclassification (threshold ratio t/l of 2.88), and linear combination of corresponding current density components yielded 8% misclassification (threshold ratio t/l of 1.04). Anodal and cathodal thresholds were not significantly different (p = 0.39). Potential gradient, current density, and energy strength-duration curves were constructed for pulse durations (D) of 0.2-20 msec. The best fit hyperbolic curve for current density magnitude (Jm) was Jm = 3.97/D + 3.15, where Jm is in mA/cm2, and D is in msec. Thus, for stimulation during electrical diastole 1) both current density magnitude and longitudinal and transverse components of the potential gradient are closely correlated with excitation, 2) the extracellular potential gradient along cardiac cells has a lower threshold than across cells, while current density thresholds along and across cells are similar, 3) anodal and cathodal thresholds are approximately equal for stimuli greater than or equal to 5 mA, and 4) the extracellular potential gradient, current density, and energy excitation thresholds can be expressed by strength-duration equations.

Mechanism of ventricular vulnerability to single premature stimuli in open-chest dogs.

To determine the mechanism of ventricular vulnerability to electrical stimulation, we simultaneously recorded from 120 transmural electrodes in a 35 X 20 X 5-mm portion of right ventricular infundibulum in seven dogs. Baseline pacing (S1) was performed from outside the mapped region followed by single premature stimulation (S2) of increasing strength at the center of the mapped region. In five of six episodes of ventricular fibrillation and 26 of 30 episodes of repetitive responses, complete reentrant pathways were observed. Earliest activation following S2 was not at the site of S2 stimulation but was at a point between the S1 and S2 sites of stimulation. Activation spread away from the early site toward the opposite side of the mapped region around the sides of an arc of block near the S2 site to form a "figure-of-eight." The activation fronts coalesced to activate the region around the S2 site last and, if the difference in times between activation at the early site and near the S2 site was large, reentered the tissue toward the S1 site. Ventricular refractory periods were determined in four dogs following S1 pacing; the regions with the greatest nonuniformity in the dispersion of refractoriness were not the regions of unidirectional block after S2 stimulation. Thus, 1) ventricular fibrillation and repetitive responses induced electrically with S1 and S2 stimuli at different ventricular sites arise by figure-of-eight reentry, 2) this reentry is caused by the ability of S2 stimulation both to prolong refractoriness near the S2 site and to initiate a propagated response in the region between the S1 and S2 sites, and 3) a nonuniform dispersion of refractoriness is not crucial for the electrical induction of reentry leading to ventricular fibrillation or repetitive responses when S1 and S2 stimuli are given at different locations on the right ventricular outflow tract.

Improved defibrillation thresholds with large contoured epicardial electrodes and biphasic waveforms.

A reduction in the shock strength required for defibrillation would allow use of a smaller automatic implantable cardioverter-defibrillator and would reduce the possibility of myocardial damage by the shock. Most internal defibrillation electrodes require 5 to 25 J for successful defibrillation in human beings and in dogs. In an attempt to lower the shock strength needed for defibrillation, we designed two large titanium defibrillation patch electrodes that were contoured to fit over the right and left ventricles of the dog heart, covering areas of approximately 33 and 39 cm2, respectively. In six anesthetized open-chest dogs, the electrodes were secured directly to the epicardium and ventricular fibrillation was induced by 60 Hz alternating current. Truncated exponential monophasic and biphasic shocks were given 10 sec later and defibrillation thresholds (DFTs) were determined. The DFT was 159 +/- 48 V, 3.2 +/- 1.9 J (mean +/- SD) for 10 msec monophasic shocks and 106 +/- 22 V, 1.3 +/- 0.4 J, for biphasic shocks with both phase durations equal to 5 msec (5-5 msec). The experiment was repeated in another six dogs in which the electrodes were secured to the pericardium. The mean DFT was not significantly higher than that for the electrodes on the epicardium: 165 +/- 27 V, 3.1 +/- 1.2 J for 10 msec monophasic shocks and 116 +/- 19 V, 1.6 +/- 0.5 J for 5-5 msec biphasic shocks. Low DFTs were also obtained with biphasic shocks in which the duration of the first phase was longer than that of the second.(ABSTRACT TRUNCATED AT 250 WORDS)

The potential gradient field created by epicardial defibrillation electrodes in dogs.

Knowledge of the potential gradient field created by defibrillation electrodes is important for the understanding and improvement of defibrillation. To obtain this knowledge by direct measurements, potentials were recorded from 60 epicardial, eight septal, and 36 right ventricular transmural electrodes in six open-chest dogs while 1 to 2 V shocks were given through defibrillation electrodes on the right atrium and left ventricular apex (RA. V) and on the right and left ventricles (RV .LV). The potential gradient field across the ventricles was calculated for these low voltages. Ventricular fibrillation was electrically induced, and ventricular activation patterns were recorded after delivering high-voltage shocks just below the defibrillation threshold. With the low-voltage shocks, the potential gradient field was very uneven, with the highest gradient near the epicardial defibrillation electrodes and the weakest gradient distant from the defibrillation electrodes for both RA. V and RV .LV combinations. The mean ratio of the highest to the lowest measured gradient over the entire ventricular epicardium was 19.4 +/- 8.1 SD for the RA. V combination and 14.4 +/- 3.4 for the RV .LV combination. For both defibrillation electrode combinations, the earliest sites of activation after unsuccessful shocks just below the defibrillation threshold were located in areas where the potential gradient was weak for the low-voltage shocks. We conclude that there is a markedly uneven distribution of potential gradients for epicardial defibrillation electrodes with most of the voltage drop occurring near the electrodes, the potential gradient field is significant because it determines where shocks fail to halt fibrillation, and determination of the potential gradient field should lead to the development of improved electrode locations for defibrillation.

Comparison of the defibrillation threshold and the upper limit of ventricular vulnerability.

To examine the relationship between the defibrillation threshold and the strength of shocks that induce ventricular fibrillation during the vulnerable period, we determined the defibrillation threshold in 22 open-chest dogs using epicardial defibrillation electrodes with the cathode at the ventricular apex and the anode at the right atrium. We also determined whether there was an upper limit of shock strength that induces fibrillation in the vulnerable period by giving shocks of various energy through these same electrodes during the repolarization phase of paced rhythm. The above determinations were also made with the anode at the ventricular apex and the cathode at the right atrium in eight of the dogs and with the cathode at the ventricular apex and the anode at the left atrium in another eight of the dogs. In all dogs for all electrode configurations, there was an upper limit to the shock strength that induced ventricular fibrillation during the vulnerable period. Depending on the electrode combination, this upper limit of ventricular vulnerability either was not significantly different from or was slightly lower than the defibrillation threshold. The correlation coefficient between the two was highly significant for all three electrode configurations. These results support the hypothesis that successful defibrillation with epicardial electrodes requires a shock strength that reaches or exceeds the upper limit of ventricular vulnerability and that shocks slightly lower than the defibrillation threshold fail because they reinitiate ventricular fibrillation by stimulating portions of the myocardium during their vulnerable period.

Activation during ventricular defibrillation in open-chest dogs. Evidence of complete cessation and regeneration of ventricular fibrillation after unsuccessful shocks.

To test the hypothesis that a defibrillation shock is unsuccessful because it fails to annihilate activation fronts within a critical mass of myocardium, we recorded epicardial and transmural activation in 11 open-chest dogs during electrically induced ventricular fibrillation (VF). Shocks of 1-30 J were delivered through defibrillation electrodes on the left ventricular apex and right atrium. Simultaneous recordings were made from septal, intramural, and epicardial electrodes in various combinations. Immediately after all 104 unsuccessful and 116 successful defibrillation shocks, an isoelectric interval much longer than that observed during preshock VF occurred. During this time no epicardial, septal, or intramural activations were observed. This isoelectric window averaged 64 +/- 22 ms after unsuccessful defibrillation and 339 +/- 292 ms after successful defibrillation (P less than 0.02). After the isoelectric window of unsuccessful shocks, earliest activation was recorded from the base of the ventricles, which was the area farthest from the apical defibrillation electrode. Activation was synchronized for one or two cycles following unsuccessful shocks, after which VF regenerated. Thus, after both successful and unsuccessful defibrillation with epicardial shocks of greater than or equal to 1 J, an isoelectric window occurs during which no activation fronts are present; the postshock isoelectric window is shorter for unsuccessful than for successful defibrillation; unsuccessful shocks transiently synchronize activation before fibrillation regenerates; activation leading to the regeneration of VF after the isoelectric window for unsuccessful shocks originates in areas away from the defibrillation electrodes. The isoelectric window does not support the hypothesis that defibrillation fails solely because activation fronts are not halted within a critical mass of myocardium. Rather, unsuccessful epicardial shocks of greater than or equal to 1 J halt all activation fronts after which VF regenerates.