Effects of Transvenous Electrode Polarity and Waveform Duration on the Relationship Between Defibrillation Threshold and Upper Limit of Vulnerability
Background The upper limit of vulnerability (ULV) hypothesis for defibrillation predicts that maneuvers that alter the ULV will cause a similar alteration in the defibrillation threshold (DFT). The purpose of this study was to test this prediction by evaluating the effects of electrode polarity and waveform duration on the relationship between the DFT and the ULV.
Methods and Results Platinum spring electrodes were placed in the right ventricular (RV) apex and the superior vena cava in 12 pigs. Strength-duration curves were constructed for the DFT and ULV for each electrode polarity with monophasic waveforms (6 pigs) of different durations (2 to 14 ms) and biphasic truncated exponential waveforms (6 pigs) having phase 1 equal to 4 ms and phase 2 of different durations (0 to 10 ms). ULV data were gathered by scanning of the T wave. The ventricular pacing threshold (VPT) and ventricular fibrillation threshold (VFT) were also determined with these same waveforms. For the RV electrode as a cathode for monophasic and the first phase of biphasic stimuli, VPTs for the same waveform duration were significantly lower than for the configuration with the RV electrode as an anode. VFTs were not significantly different for the two electrode polarities with either monophasic or biphasic waveforms. The DFT changed in a fashion similar to the ULV with changes in electrode polarity and phase duration for both monophasic and biphasic waveforms. The ULV and DFT for each waveform duration for each polarity were strongly correlated (r=.83 to .99).
Conclusions The almost identical changes in ULV and DFT with changes in electrode polarity and waveform duration provide new evidence to support the ULV hypothesis of defibrillation.
The ULV hypothesis1 2 has been proposed to explain the mechanism of ventricular defibrillation. The hypothesis asserts that unsuccessful shocks slightly weaker than necessary to defibrillate halt all activation fronts during VF. However, the same shock also stimulates regions of the myocardium that have just recovered excitability and hence are in their vulnerable period. The shock initiates new activation fronts in this vulnerable myocardium that reinitiate VF. To successfully defibrillate, the shock strength must be greater than the largest shock that reinitiates fibrillation. The strength of this largest shock is called the ULV.
The ULV hypothesis states that the shock strength at the ULV should be correlated with the shock strength required for defibrillation. Indeed, a significant correlation between the DFT and ULV has been observed in both animals1 2 and humans.3 4 5 6 The hypothesis also suggests that factors that affect the DFT should have a parallel effect on the ULV. This has been confirmed to a limited extent in studies that changed the DFT by altering the field strength distribution (with two different defibrillation electrode configurations)1 7 or the electrophysiological state of the myocardium (with lidocaine or procainamide infusion)7 8 and found that the ULV changed similarly, so that the DFT and the ULV remained closely correlated.
Electrode polarity and waveform duration have been reported to affect defibrillation efficacy for both monophasic and biphasic shocks in clinical and animal studies.9 10 11 12 13 However, their effect on the ULV remains unknown. The purpose of the present study was to compare the ULV and the DFT for each electrode polarity with monophasic and biphasic waveforms of different durations. The ULV hypothesis of defibrillation would be supported if electrode polarity and waveform duration change the ULV in proportion to changes in the DFT. To further explore the effect of transvenous lead electrode polarity and waveform duration on other electrophysiological characteristics of the myocardium, we also determined the VFT (ie, the lower limit of vulnerability) and the VPT for each electrode polarity for the same waveforms for which the ULV and DFT were determined.
This study consisted of two protocols. Protocol 1 studied monophasic waveforms, and protocol 2 studied biphasic waveforms. The two protocols used the same methods for animal preparation and VPT, VFT, DFT, and scanned ULV measurement methods. All studies were performed in accordance with the guidelines established in the Position of the American Heart Association on Research Animal Use adopted by the American Heart Association on November 11, 1984.
Twelve pigs weighing 21 to 30 kg (27±3.2 kg, mean±SD) were tranquilized with 22 mg/kg ketamine and 1.1 mg/kg acepromazine IM. Subsequently, anesthesia was maintained with sodium pentobarbital at a 10-mg/kg IV initial dose followed by a continuous infusion of 0.05 mg·kg−1·min−1 IV. Succinylcholine was initially given at a dose of 1 mg/kg and later at 0.25 to 0.5 mg/kg at about 10-minute intervals to decrease muscle contractions induced by defibrillation shocks. Each pig was intubated with a cuffed endotracheal tube and ventilated with a mixture of room air and oxygen through a Harvard respirator (Harvard Apparatus Co). A femoral arterial line was inserted with a catheter connected to a Statham transducer (Gould Inc) to continuously monitor systemic arterial blood pressure. Blood pressure and the lead II surface ECG were continuously displayed on a monitor (VSM 1, Physio-Control Corp). Body temperature was monitored continuously from the esophagus and maintained within normal limits with a heated water circulating mat. Normal saline was continuously infused (2 to 5 mL·kg−1·min−1). Normal metabolic status was maintained throughout the study by taking blood every 30 to 60 minutes; determining the pH, Po2, Pco2, base excess, CO2 and HCO3− contents and calcium, potassium, and sodium concentrations; and correcting any abnormal values.
Electrodes and Waveforms
The pigs were laid on their backs. Both external jugular veins were surgically exposed. Catheter-mounted platinum-coated titanium coil electrodes were used, one 34 mm long (surface area, 390 mm2) and the other 68 mm long (surface area, 780 mm2; Cardiac Pacemaker Inc). The catheter with the 34-mm electrode was inserted into the right jugular vein and was advanced to the RV apex. This electrode is referred to as the RV electrode. The catheter with the 68-mm electrode was inserted into the left jugular vein. The distal tip was positioned at the junction of the SVC and the right atrium. This electrode is referred to as the SVC electrode. The position of the catheters was verified with fluoroscopy.
Protocol 1. Most clinical reports and animal studies suggest that the DFT of monophasic waveforms is lower with the RV electrode as anode than as cathode.9 10 14 To test whether the electrode polarity of monophasic waveforms has the same effect on the ULV, DFTs and ULVs were determined in 6 pigs by use of truncated exponential monophasic waveforms with durations of 2, 4, 6, 8, 11, and 14 ms (Fig 1A⇓).
Protocol 2. The effect of electrode polarity on biphasic waveforms for defibrillation is controversial. Our previous study13 suggested that because of their low DFTs, for phase durations most commonly used clinically, changing the polarity of biphasic waveforms did not change the DFT. For biphasic waveforms with phase 2 at least 2 ms longer than phase 1 that had high DFTs, the DFT was lower when the RV electrode was an anode during phase 2, similar to the polarity difference for a monophasic waveform, suggesting that a long second phase of a biphasic waveform defibrillates in a fashion similar to monophasic waveforms. To test whether the phase 2 duration and polarity of biphasic waveforms influence the ULV in proportion to the effects on the DFT, truncated exponential biphasic waveforms with a phase 1 duration of 4 ms and a phase 2 duration of 0, 2, 4, 6, 8, and 10 ms were studied in another 6 pigs. For biphasic waveforms, the leading edge of phase 2 began 0.25 ms after the trailing edge of phase 1 and was the same voltage (±5 V) as the trailing edge for phase 1 (Fig 1B⇑), thereby simulating a single capacitor waveform.
The VPT was determined by measuring the late diastolic threshold after delivery of 10 basic S1 drive stimuli (unipolar 5-ms monophasic pulses) given with a cycle length of 300 ms, delivered between an electrode at the tip of the catheter in the RV and the SVC electrode. The VPT was determined 280 ms after the last S1 stimulus with either monophasic (protocol 1) or biphasic (protocol 2) stimuli (S2)15 with a waveform shape identical to that of the waveforms used for determining the ULV and DFT. The sequence within and between animals for determining the VPT for S2 waveforms was randomized. All stimuli were given with a specially constructed stimulator that could deliver any desired waveform.
The VFT for each waveform was determined after the VPT was found. First, the times from the pacing stimulus to the beginning, peak, and end of the T wave were measured with an oscilloscope using limb lead II or III. The beginning of the T wave was defined as the first notable change in slope in the electrogram after the ST segment. The end of the T wave was defined as the last notable change in slope in the electrogram that preceded the interbeat pause. The peak of the T wave was defined as the absolute maximum observed between the beginning and end of the T wave. A new measurement of the T wave was taken after every five fibrillation episodes. This process was also applied during ULV determination.
The VFT was determined by a premature S2 stimulus given after a series of regularly spaced S1 stimuli of twice diastolic current threshold given with a cycle length of 300 ms. A premature S2 stimulus of 10 mA was then given with a coupling interval of 280 ms. The S1 and S2 stimuli were delivered from the same stimulator and through the same electrodes as used for determining the VPT. The coupling interval between the last S1 stimulus and the S2 stimulus (the S1-S2 interval) was decremented in 10-ms steps from 280 ms until either VF was induced or a propagated ventricular response did not occur, as determined by observation of the surface ECG. If VF was not induced, the S2 current was increased by 10 mA and the S1-S2 interval was again decremented from 280 ms in 10-ms steps until either VF was induced or ventricular capture did not occur. The S2 current was increased in 10-mA steps, and this procedure was repeated until VF was induced. The S2 stimulus strength was then decreased to 10 mA below the level that induced VF and was serially incremented in 2 mA steps, and the S1-S2 interval was decremented as before until VF was again induced. The lowest current strength that induced VF was called the VFT. The coupling interval at which this strength stimulus induced fibrillation was noted, and its relation to the peak of the T wave was recorded. After VF was induced, a rescue biphasic shock at the minimum reliable defibrillation strength (typically 400 to 500 V) was given immediately through the catheter system used for ULV and DFT determination. The S2 waveforms for VFT determination were monophasic (protocol 1) and biphasic (protocol 2) waveforms of the same shape as that used for ULV and DFT determination and calculated from the impedance measured during a defibrillation shock given after 10 seconds of VF with a 600-V monophasic shock of 6-ms duration with the RV electrode as the anode. The order of determining the VFTs of different S2 waveforms was randomized separately from the order of determining the VPTs.
A multichannel stimulator was used to deliver constant-current S1 stimuli at twice cathodal diastolic threshold. S1 pacing was performed with a cycle length of 80% of the intrinsic RR interval observed after determination of the VPT and VFT. Another channel of the stimulator was used to deliver a premature stimulus (S2) at predetermined S1-S2 coupling intervals. The stimulator was the source of an external signal to trigger the delivery of high-voltage truncated exponential electric shocks via an external defibrillator (HVS-02, Ventritex) to the endocardial electrodes for the attempted induction of VF. The ULV was determined by the delivery of shocks timed to scan all of the T wave in the following sequence. The S1-S2 coupling intervals were scanned starting with the first S2 stimulus given at the peak of the T wave. ULV shocks were then delivered alternately before and after the peak of the T wave, the coupling intervals being selected to move the stimuli away from the peak in 10-ms steps. For example, if the coupling interval at the peak of the T wave was 200 ms, then the subsequent coupling intervals were 210 ms, 190 ms, 220 ms, 180 ms, 230 ms, 170 ms, etc, until the limits of the T wave were encountered or VF was induced.
Shock strength was initially set to the mean leading-edge voltage for the ULV from previous studies. If the ULV stimulus strength induced VF at any coupling interval, then the shock strength was increased 40 V and the coupling interval was reset to the peak of the T wave. Thereafter, the shock strength was increased after each VF episode until a shock strength was reached that did not induce VF at any S1-S2 coupling interval throughout the T wave. The next scanned ULV measurement was started 20 V lower than the shock strength that did not induce VF at any coupling interval. If the first ULV stimulus strength did not induce VF at any coupling interval, then the shock strength was decreased 40 V and the coupling interval was reset to the peak of the T wave. Thereafter, successively weaker shocks were delivered at all coupling intervals until VF was induced. The next scanned ULV shock was set 20 V higher than the shock strength that induced VF. Successive ULV test shocks were separated by 15 seconds.16 The lowest shock strength that did not induce fibrillation at any coupling interval tested was defined as the ULV. The coupling interval at which fibrillation was induced with a shock strength 20 V lower than the ULV and its relation to the peak of the T wave were also recorded.
It has been demonstrated that DFT data gathered from episodes of ULV-induced VF are not significantly different from other DFT data.8 Therefore, after a ULV test shock initiated VF, a defibrillation shock was given 10 seconds later with the identical waveform. If the episodes of ULV-induced VF were not sufficient to complete the corresponding DFT determination, VF was induced with 30-V, 60-Hz alternating current given through the two defibrillating catheter electrodes. The first attempt to defibrillate the animal was made with the leading-edge voltage of the shock adjusted to the mean value of the DFT from previous experiments. Depending on the success or failure of the shock, the leading-edge voltage was decreased or increased, respectively, by 40 V. When the transition from failure to success or success to failure occurred, a final shock was tested midway between the last successful and unsuccessful shocks (a 20-V step). The lowest-strength successful shock was taken as the DFT. At least 4 minutes elapsed after every fibrillation-defibrillation episode. More time was permitted, if necessary, to allow the blood pressure and heart rate to return to normal.
The current and voltage waveforms delivered to the electrodes were measured by isolation and recording of the voltage across a 0.25-Ω resistor in series with the electrodes and a 200:1, 1.5-MΩ resistor divider in parallel with the electrodes. These waveforms were digitized at 20 kHz and recorded by a waveform analyzer (model 6100, Data Precision), which also measured the delay between the two phases delivered. Signal analysis programs within the analyzer were used to obtain impedance and energy measurements.
Two polarity configurations were compared in both protocols: RV electrode as anode and SVC electrode as cathode (RV+SVC−), and RV electrode as cathode and SVC electrode as anode (RV−SVC+). The polarity configuration for biphasic waveforms refers to the first phase. Biphasic waveform durations are given by the notation “phase 1 duration/phase 2 duration,” eg, a 4/10-ms waveform means that the first phase lasted 4 ms and the second phase lasted 10 ms.
VPTs were evaluated first, followed by VFTs second. ULV and DFT determinations were then done concurrently. The order of testing of waveforms was randomized by drawing two chits, one for waveform duration and the other for polarity. After the ULV and DFT were determined with the initial polarity for that waveform, ULV and DFT were determined for the other polarity. At the end of each study, the pigs were killed by electrically induced VF. The hearts were removed and weighed.
Measured values of VPT, VFT, ULV, and DFT are expressed as the mean±SD. The data for each polarity were compared by a paired Student’s t test. The paired t test and linear regression analysis were used to compare the ULV and DFT for the same waveform duration and polarity (SPSS Inc). Repeated-measures ANOVA was used to test the effect of waveform duration on the above parameters for a particular polarity (SPSS Inc). The χ2 test was used to compare the S2 timing relative to the peak of the T wave for the VFT and ULV. Equality of variances of the ULV and VFT values was tested with the F statistic. For all analyses, a value of P≤.05 was considered statistically significant.
Ventricular Pacing Threshold
The VPTs determined with monophasic waveforms (protocol 1) were significantly lower with a cathode at the RV electrode than with an anode at the RV electrode for all waveform durations (P<.01, Table⇓). The VPTs determined with biphasic waveforms (protocol 2) were also significantly lower with the first phase a cathode rather than an anode at the RV electrode for all second-phase durations (P<.01, Table⇓). Thus, the effect of polarity on excitability was the same for the first phase of the biphasic waveform as for the monophasic waveform. For each electrode polarity, the VPT was not significantly different for different waveform durations for either monophasic or biphasic waveforms.
Ventricular Fibrillation Threshold
Reversing electrode polarity caused no statistically significant difference in mean VFTs for either monophasic (protocol 1) or biphasic (protocol 2) waveforms (Table⇑). The S1-S2 coupling intervals for induction of VF were also not significantly different for the two shock polarities in either protocol 1 or protocol 2. For 89% of monophasic and 100% of biphasic VF inductions, the S2 was given before the peak of the T wave (Figs 2⇓ and 3⇓). For an individual animal, the VF was often induced with the same S1-S2 interval for all waveform durations of both polarities.
Upper Limit of Vulnerability and Defibrillation Threshold
Strength-duration curves for the ULV and DFT at each electrode polarity were constructed by plotting leading-edge voltage and delivered energy versus waveform duration (Figs 4⇓ and 5⇓). For the monophasic waveforms having a duration >2 ms, mean DFT was significantly higher when the RV electrode was a cathode than when it was an anode (P<.01, Fig 4⇓). With the biphasic waveforms in protocol 2, however, the DFTs were not different (P>.05) for either electrode polarity for phase 2 durations of 2 and 4 ms. When phase 2 was at least 2 ms longer than phase 1, changes in polarity or duration of phase 2 altered the DFT the same way as changes in polarity or duration altered the DFT for monophasic shocks. That is, the DFTs with phase 2 a cathode at the RV electrode increased dramatically as the duration of phase 2 was at least 2 ms longer than phase 1 (Fig 5⇓).
For each waveform tested, the ULV value tended to be slightly higher than the corresponding DFT, although these differences reached statistical significance only for the 4/6-ms waveforms with a first-phase anode at the RV electrode and the 4/8- and 4/10-ms waveform with a first-phase cathode at the RV electrode (Fig 5⇑). The changes in ULV with changes in electrode polarity and waveform duration were almost identical to the changes in DFT. The relation between the ULV and DFT for each waveform at each electrode polarity was strongly correlated (r ranged from .83 to .99). We pooled all the individual ULV and DFT data for all waveform durations with the same electrode polarity in each protocol and calculated the linear regression (Figs 6⇓ and 7⇓). The relationships between the ULV and DFT for the pooled data were strongly correlated for each polarity (r=.94 and .96 for anodal and cathodal monophasic waveforms and r=.91 and .89 for anodal and cathodal biphasic waveforms, respectively).
During scanning of the T wave while the ULV was determined, the coupling interval of the strongest shock that induced VF (the shock voltage 20 V lower than the ULV shock strength) was not significantly different when the RV electrode was an anode or when it was a cathode for both monophasic and biphasic waveform protocols. Therefore, we pooled the coupling interval data of both electrode polarities in each protocol to construct a histogram to analyze the timing relative to the peak of the T wave of these strongest shocks that induced VF (Figs 2⇑ and 3⇑). For 92% of monophasic VF inductions and 78% of biphasic VF inductions, the S2 was given after the peak of the T wave, with the highest percentage of shocks occurring 20 ms after the peak of the T wave. In contrast to the VFT determination in which VF was induced with relatively stable S1-S2 coupling intervals for all waveforms, for the ULV determination, the S1-S2 coupling interval varied more with different waveform durations and even with the same waveform duration for different animals. Thus, the histogram of the ULV coupling intervals was more dispersed than for the VFT (P<.05, F statistic, Figs 2⇑ and 3⇑). By χ2 test, there was a highly significant difference between the VFT and ULV in the timing of the S2 shocks relative to the peak of the T wave (P<.0001).
The ULV hypothesis is one of several hypotheses that have been proposed to explain the mechanism by which a defibrillation shock halts fibrillation.1 This hypothesis is based on the observation that shocks much weaker than needed to defibrillate can induce fibrillation when given during the vulnerable period of normal or paced rhythm.17 Since VF is thought to be maintained by reentry,18 which means that activation fronts are continuously present, then some tissue should be in its vulnerable period at all times during fibrillation. Therefore, no matter when a defibrillation shock is given, some part of the heart should be in its vulnerable period. Yet if the shock is sufficiently strong, fibrillation is halted without the shock simultaneously reinitiating fibrillation by stimulating this vulnerable tissue. These considerations suggest that there is a shock strength, called the ULV, above which shocks do not initiate fibrillation even though given to tissue in its vulnerable period. A ULV has been shown to exist in the atria19 and ventricles in animals1 20 21 and in humans.3 4 5 6
The ULV is thought to occur when the shock electric field is so strong that, in addition to stimulating new action potentials in more recovered tissue, it also causes action potential prolongation in less recovered tissue.22 23 24 25 26 Such action potential prolongation will extend the refractory period of the tissue but for a shorter time period than will a new action potential.27 Refractory period extension is thought to have an antifibrillatory effect by (1) preventing the initiation of new activation fronts by the shock28 29 and/or (2) decreasing the dispersion of refractoriness so that any activation fronts after the shock are less likely to block and initiate reentry.23 30
The ULV hypothesis for defibrillation states that two requirements are necessary for a shock to defibrillate. One, the shock must halt a sufficient number of activation fronts present at the time of the shock so that fibrillation cannot be maintained after the shock. Two, the shock itself, by stimulating tissue in its vulnerable period, must not initiate new activation fronts that reinitiate fibrillation.1 The ULV hypothesis states that a higher shock strength is needed to satisfy the second than the first requirement, so it is the second requirement that determines the DFT.
The ULV hypothesis leads to two predictions that can be experimentally tested. One prediction is that factors that change the DFT should change the ULV in a similar fashion. A second prediction is that, when the ULV is determined by scanning the entire vulnerable period, the DFT and ULV should be similar in magnitude, with the ULV slightly greater than the DFT. The ULV should be slightly greater than the DFT because scanning of the entire vulnerable period should systematically search the T wave so that one of the shocks is likely to be given at the time the tissue in which the shock field has its weakest effect is in its vulnerable period. Shocks given during fibrillation to determine the DFT may, by chance, be given when this tissue is not in its vulnerable period so that the shock will succeed because it halts the activation fronts of fibrillation without reinitiating fibrillation in this tissue. As described in more detail elsewhere,31 these considerations suggest that the ULV should be above the 90% success point on the defibrillation probability success curve, whereas the DFT should be nearer the 50% success point.
Several previous studies have compared the absolute values of the DFT and the ULV for a single-electrode configuration and a single shock waveform.2 3 8 31 32 33 Some of the studies scanned the entire vulnerable period, while others gave shocks at only a few times during the T wave. Although most of these studies found that the ULV either was not significantly different from or was slightly greater than the DFT,2 31 33 a few studies found that the ULV differed markedly from the DFT and frequently was lower than the DFT.3 32 Only a few studies have performed an intervention to alter the DFT to see whether the ULV was similarly altered.1 7 8 These interventions include changing the locations of the defibrillation electrodes1 7 and administering procainamide7 or lidocaine.8 These interventions all caused parallel changes in the DFT and ULV.
The purpose of this study was to alter two fundamental qualities of monophasic and biphasic waveforms that have a striking effect on the DFT, ie, waveform duration and polarity, to determine whether similar changes occurred in the ULV and DFT, as predicted by the ULV hypothesis. This study made many more comparisons of the DFT and ULV than have previously been made in a single study; the DFT and ULV were compared for 12 different monophasic and 12 different biphasic combinations of waveform duration and polarity.
For short monophasic waveforms (2 ms), the DFT was not significantly different for the two waveform polarities, but for all waveform durations tested that were longer than 2 ms, the DFT was significantly lower, with the RV electrode an anode rather than a cathode (Fig 4⇑). We have previously reported this finding that waveform duration affects the influence of waveform polarity for defibrillation electrodes in the RV and SVC.13 The changes in the ULV were almost identical to the changes in the DFT (Fig 4⇑) for all monophasic waveform combinations of duration and polarity tested. The mean DFT and mean ULV were not significantly different for each combination, although in most cases the mean ULV was slightly higher than the mean DFT.
Parallel changes were seen in the DFT and ULV for biphasic waveforms also. When the first phase of the biphasic waveform was given alone (the 4/0-ms waveform), both the DFT and the ULV were lower when the RV electrode was an anode than when it was a cathode (Fig 5⇑). This result is similar to that observed for the 4-ms monophasic waveform in protocol 1 (Fig 4⇑). Adding a second phase that was equal to or shorter than the first phase (2 and 4 ms) sharply decreased both the DFT and the ULV. For these highly efficient biphasic waveforms, altering shock polarity had no significant effect on either the DFT or the ULV. Although we have reported this result for the DFT, it has not been previously reported for the ULV.13 As the second phase of the biphasic waveform is increased in duration so that it becomes progressively longer than the first phase, the DFT increases for both polarities, but it increases much more markedly for the shock polarity with the RV electrode as an anode. Therefore, for biphasic waveforms with a second phase longer than the first phase, the shock polarity with the lower DFT occurs when the second phase is an anode, which is the same polarity that exhibits a lower DFT for monophasic waveforms. On the basis of these findings, it has been suggested that, when the second phase of a biphasic waveform becomes too large, the beneficial effect of the combination of the two phases is lost and the second phase must defibrillate in a manner similar to that of a monophasic shock.13 Therefore, the leading-edge voltage of the second phase must be at least equal to the leading-edge voltage of a monophasic waveform to defibrillate. This waveform is highly inefficient for defibrillation because the first phase, which has a leading-edge voltage higher than the second-phase leading-edge voltage, is wasted.
As the phase 2 duration was increased, similar changes were observed in the ULV as in the DFT (Fig 5⇑). In all cases, the ULV was either greater than or not significantly different from the DFT. This finding suggests that for unsuccessful defibrillation attempts with biphasic waveforms in which the second phase is larger than the first, it is the second phase that initiates fibrillation by stimulation during the vulnerable period.
For both monophasic and biphasic waveforms, shocks one step lower in voltage than the ULV induced fibrillation when given after the peak of the T wave, whereas the much weaker shocks of VFT voltage typically induced fibrillation when given before the peak of the T wave (Figs 2⇑ and 3⇑). The time during the T wave in which a shock initiates fibrillation probably depends on at least two factors: the shock field induced by the S2 electrodes and the distribution of refractoriness after stimulation by the S1 electrodes. In this study, S1 and S2 were both given via electrodes in the RV apex. With this electrode location, the RV apex activates earlier than the more distal LV, and the RV apex is also exposed to a stronger S2 shock electrical field than is the LV.34 Since the RV apex activates earlier than the LV, it should recover earlier also. Thus, the RV apex probably passes through its vulnerable period during the first half of the T wave, whereas a major portion of the LV passes through its vulnerable period during the second half of the T wave. As the S2 shock strength is increased from very low levels, fibrillation probably first occurs where the shock strength exceeds a particular value in tissue that is in its vulnerable phase. As S2 strength is increased, this will first occur close to the S2 electrode in the RV apex. Because this tissue is probably in its vulnerable period before the peak of the T wave, VFT-strength shocks induce fibrillation at this time.
The ULV is thought to occur when the shock electric field exceeds a particular value throughout the ventricles.35 Shocks slightly weaker than the ULV should create an electric field that exceeds this required value everywhere except where the shock field is weakest, which for the electrode configuration used in this study is distant from the RV apical electrode in the lateral LV free wall.34 This region should be in its vulnerable period after the peak of the T wave. Therefore, with the S1 and S2 electrode configurations used in this study, shocks slightly lower than the ULV would be expected to induce fibrillation after the peak of the T wave.
Neither the VPT nor the VFT was significantly changed by changes in the waveform duration for both monophasic and biphasic waveforms (Table⇑). These findings suggest that the waveform durations tested in this study (2 to 14 ms for the monophasic waveforms) are on the flat portions of the strength-duration curves, indicating that the time constants for the strength-duration curves for the VPT and the VFT are both quite short for these truncated exponential waveforms. The VPT was lower when the RV electrode was a cathode for the monophasic and the first phase of biphasic waveforms. In contrast, the VFT was not affected by polarity for either monophasic or biphasic waveforms. The myocardium in which activation fronts first arise after electrical stimulation of VPT or VFT strength is near the stimulating electrode.36 In contrast, the myocardium from which activation fronts first arise after electrical stimuli slightly lower than DFT and ULV strength is usually distant from the stimulating electrode.21 This difference may be one reason why the effects of waveform duration and polarity on the DFT and ULV are different from the effects on the VPT and VFT. Whether the stimulating electrode is an anode or a cathode, it has been shown that both hyperpolarization and depolarization occur in the tissue just a few millimeters away from the stimulating electrode in the form of a “dog bone” pattern.37 The distribution of hyperpolarization and depolarization in the portions of the myocardium distant from the stimulating electrodes has not yet been reported.
Previous studies that have examined the effect of polarity on defibrillation energy requirements for transvenous electrode systems have reported conflicting results. Some studies report that the DFT is lower when the RV electrode is an anode.10 12 38 Other studies have found that changing polarity does not significantly alter the DFT for biphasic waveforms.39 40 A few other studies suggest that in some patients, the threshold is lower with the RV electrode an anode, whereas in other patients the threshold is lower with this electrode as a cathode.41 42 Although in this study, the DFT was lower for biphasic waveforms with a second phase ≤4 ms when the RV electrode was an anode, the difference was not significant. On the basis of these results, it might be assumed that the first phase of a biphasic waveform should be an anode at the RV, since the majority of studies found that this polarity was either better than or not significantly different from the other polarity. This assumption is valid only if these previous results are true for the particular biphasic waveform that is being tested. Our results suggest that this assumption is not true for all biphasic waveforms. When the second phase was >4 ms, the DFT was markedly higher when the first phase was an anode at the RV. Although these results support the use of an anode at the RV for the first phase if the second phase is short, they imply that great care should be taken that the second phase does not become too long, since defibrillation efficacy markedly decreases for this polarity but not for the opposite polarity. In fact, if shock polarity does not significantly change defibrillation requirements for biphasic waveforms with a short second phase in patients, as was true for animals in this study, then it would be better to initially test a biphasic waveform with the first phase a cathode at the RV in all cases. If this threshold is high, then the other polarity could be tested.
Some investigators have advocated using the ULV to estimate defibrillation shock strength requirements during implantation of a cardioverter-defibrillator.3 43 The results of this study suggest that if the implanting physician wishes to test the effect of changing the polarity of the waveform, then the ULV can still be used as a surrogate for the DFT, since the change in the ULV with polarity mirrors the change in the DFT (Figs 4⇑ and 5⇑).
Limitations of the Study
One limitation of this study is that we did not rapidly pace the heart during ULV determination as Malkin et al did.31 They found that the ULV corresponded to >90% probability of defibrillation success if it was determined with S1 pacing that was so rapid that the blood pressure dropped to zero. During slower S1 pacing, as in our study, Malkin et al found that the ULV was lower and more closely approximated the 50% probability of defibrillation success. Because we desired to test many different waveform durations for both shock polarities and because determination of the DFT requires fewer episodes of fibrillation than does determination of the probability of defibrillation success, we determined DFTs and not probability-of-success curves in this study. Since the DFT is closer to the 50% than the 90% point on the probability-of-defibrillation-success curve, we determined the ULV with slower S1 pacing. Another reason for not using rapid S1 pacing is that we wanted to minimize the amount of time that the animals were hypotensive. Although in almost all cases, for both monophasic and biphasic waveforms, the ULV was higher than the DFT, this difference was significant only for some waveform durations and polarities with biphasic waveforms (Fig 5⇑). One possible reason for this difference is that the ULV is higher or the DFT is lower on the biphasic probability-of-success curve than on the monophasic curve. We have no data to support this speculation, however.
A second possible limitation is that we used two different techniques to induce VF during DFT determination. One was the induction of fibrillation by strong shocks during ULV determinations, and the other was 60-Hz stimulation. The findings from a previous study suggest that the use of fibrillation episodes induced during ULV testing does not influence the DFT determination.8 Therefore, we do not believe that the use of both techniques for inducing fibrillation markedly influenced our results. Successive ULV test shocks were separated by 15 seconds in the study. Usually, blood pressure returned to normal in <3 seconds of this interval.
Altering the duration and polarity of monophasic and biphasic waveforms caused striking and parallel changes in the DFT and the ULV that were nearly equal in magnitude. The marked similarity of the changes in the DFT and ULV supports the ULV hypothesis for defibrillation, which predicts that the shock strength needed to defibrillate is determined by and is equal to the maximum shock strength that can induce fibrillation by stimulating cardiac tissue during its vulnerable period.
Selected Abbreviations and Acronyms
|RV||=||right ventricle, right ventricular|
|SVC||=||superior vena cava|
|ULV||=||upper limit of vulnerability|
|VFT||=||ventricular fibrillation threshold|
|VPT||=||ventricular pacing threshold|
This study was supported in part by National Institutes of Health research grant HL-42760; National Science Foundation Engineering Research Center grant CDR-8622201; CPI-Guidant Corp, St Paul, Minn; and Physio-Control Corp, Seattle, Wash. We thank Jim Wayland, Jeanette Bicknell, Sharon Melnick, and Robin Walker for their technical assistance.
- Received December 16, 1996.
- Revision received February 10, 1997.
- Accepted February 13, 1997.
- Copyright © 1997 by American Heart Association
Chen P-S, Shibata N, Dixon EG, Martin RO, Ideker RE. Comparison of the defibrillation threshold and the upper limit of ventricular vulnerability. Circulation. 1986;73:1022-1028.
Souza JJ, Malkin RA, Ideker RE. Comparison of upper limit of vulnerability and defibrillation probability of success curves using a nonthoracotomy lead system. Circulation. 1995;91:1247-1252.
Chen P-S, Feld GK, Kriett JM, Mower MM, Tarazi RY, Fleck RP, Swerdlow CD, Gang ES, Kass RM. Relation between upper limit of vulnerability and defibrillation threshold in humans. Circulation. 1993;88:186-192.
Stanton MS, Mehra R, Morris J, Fetter J, DeGroot P. Relationship between defibrillation threshold and upper limit of vulnerability in humans. Pacing Clin Electrophysiol. 1992;15:563. Abstract.
Bacon ME, Vitullo RN, Kasell JH, Blitchington T, Pressley JC, Smith PK, Lowe JE, Ideker RE, Wharton JM. Upper limit of vulnerability and its relationship to defibrillation threshold in humans. Pacing Clin Electrophysiol. 1992;15:530. Abstract.
Swartz JF, Karasik PE, Bacon ME, Fletcher RD. Relationship of upper limit of vulnerability to defibrillation threshold for monophasic and biphasic waveform human nonthoracotomy defibrillation. J Am Coll Cardiol. 1994;23:293. Abstract.
Topham SL, Cha Y-M, Peters BB, Chen P-S. Effects of lidocaine on relation between defibrillation threshold and upper limit of vulnerability in open-chest dogs. Circulation. 1992;85:1146-1151.
Huang J, KenKnight BH, Walcott GP, Walker RG, Smith WM, Ideker RE. Effect of electrode polarity on internal defibrillation with monophasic and biphasic waveforms using an endocardial lead system. J Cardiovasc Electrophysiol. 1997;8;161-171.
Rollins DL, Wolf PD, Ideker RE, Smith WM. A programmable cardiac stimulator. In: Murray A, Arzbaecher R, eds. Proceedings, Computers in Cardiology. Los Alamitos, Calif: IEEE Computer Society Press; 1992:507-510.
Wiggers CJ, Wégria R. Ventricular fibrillation due to single, localized induction and condenser shocks applied during the vulnerable phase of ventricular systole. Am J Physiol. 1940;128:500-505.
Moe GK. On the multiple wavelet hypothesis of atrial fibrillation. Arch Int Pharmacodyn. 1962;140:183-187.
KenKnight B, Hsu W, Heil JE, Lin Y, Ideker RE, Lang DJ. Relationship between atrial defibrillation threshold and upper limit of vulnerability in dogs. Circulation. 1994;90(suppl I):I-14. Abstract.
Shibata N, Chen P-S, Dixon EG, Wolf PD, Danieley ND, Smith WM, Ideker RE. Influence of shock strength and timing on induction of ventricular arrhythmias in dogs. Am J Physiol. 1988;255:H891-H901.
Knisley SB, Smith WM, Ideker RE. Effect of field stimulation on cellular repolarization in rabbit myocardium: implications for reentry induction. Circ Res. 1992;70:707-715.
Sweeney RJ, Gill RM, Steinberg MI, Reid PR. Ventricular refractory period extension caused by defibrillation shocks. Circulation. 1990;82:965-972.
Dillon SM. Optical recordings in the rabbit heart show that defibrillation strength shocks prolong the duration of depolarization and the refractory period. Circ Res. 1991;69:842-856.
Swartz JF, Jones JL, Jones RE, Fletcher RD. Biphasic waveforms enhance defibrillation success by prolonging refractoriness to refibrillating wavefronts. J Am Coll Cardiol. 1990;15:72A. Abstract.
Knisley SB, Hill BC. Optical recordings of the effect of electrical stimulation on action potential repolarization and the induction of reentry in two-dimensional perfused rabbit epicardium. Circulation. 1993;88:2402-2414.
Kao CY, Hoffman BF. Graded and decremental response in heart muscle fibers. Am J Physiol. 1958;194:187-196.
Zhou X, Knisley SB, Wolf PD, Rollins DL, Smith WM, Ideker RE. Prolongation of repolarization time by electric field stimulation with monophasic and biphasic shocks in open-chest dogs. Circ Res. 1991;68:1761-1767.
Zhou X, Wolf PD, Rollins DL, Afework Y, Smith WM, Ideker RE. Effects of monophasic and biphasic shocks on action potentials during ventricular fibrillation in dogs. Circ Res. 1993;73:325-334.
Dillon SM. Synchronized repolarization after defibrillation shocks: a possible component of the defibrillation process demonstrated by optical recordings in rabbit heart. Circulation. 1992;85:1865-1878.
Malkin RA, Idriss S, Walker RG, Ideker RE. Effect of rapid pacing and T-wave scanning on the relation between the defibrillation and upper-limit-of-vulnerability dose-response curves. Circulation. 1995;92:1291-1299.
Tang ASL, Wolf PD, Afework Y, Smith WM, Ideker RE. Three-dimensional potential gradient fields generated by intracardiac catheter and cutaneous patch electrodes. Circulation. 1992;85:1857-1864.
Chen P-S, Wolf PD, Dixon EG, Danieley ND, Frazier DW, Smith WM, Ideker RE. Mechanism of ventricular vulnerability to single premature stimuli in open-chest dogs. Circ Res. 1988;62:1191-1209.
Keelan ET, Sra J, Axtell K, Maglio C, Bahl VK, Jazayeri MR, Dhala A, Blanck Z, Deshpande S, Biehl M, Akhtar M. Effect of lead polarity on the defibrillation threshold of pectorally implanted cardioverter defibrillators. J Am Coll Cardiol. 1995:279A. Abstract.
Hwang C, Swerdlow CD, Kass RM, Gang ES, Mandel WJ, Peter CT, Chen PS. Upper limit of vulnerability reliably predicts the defibrillation threshold in humans. Circulation. 1994;90:2308-2314.