(Circulation. 1996;94:2268-2277.)
© 1996 American Heart Association, Inc.
Articles |
Assessing the Excitable Gap in Reentry by Resetting
Implications for Tachycardia Termination by Premature Stimuli and Antiarrhythmic Drugs
the Cardiovascular Division, Department of Medicine, University of Pennsylvania, and the Philadelphia VA Medical Center, Philadelphia, Pa.
Correspondence to Lawrence H. Frame, MD, Cardiology Section (111C), Philadelphia VAMC, University and Woodland Avenues, Philadelphia, PA 19104.
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Abstract |
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Background The shortest excitable gap during reentry may determine responses to pacing and antiarrhythmic drugs. The resetting response has been used clinically to assess the excitable gap, but it cannot directly indicate the shortest excitable gap.
Methods and Results We studied resetting in the in vitro canine atrial tricuspid ring using an adjustable reentry preparation in which the ring was cut and reconnected electronically with an adjustable delay to vary the cycle length and excitable gap. We reset the tachycardias using 31 delays in 12 experiments. Tachycardias were terminated by premature stimuli in 16 delays. The reset window overestimated the shortest excitable gap by 25±14 ms, and the maximum degree of advancement of tachycardia underestimated the shortest excitable gap by 22±11 ms. The slope of the increasing portion of the resetting response curve was steeper in tachycardias terminated by premature stimuli than in those not terminated (-0.69±0.2 versus -0.37±0.2, P<.01). The effective refractory period difference between the sites of pacing and of block correlated with the slope of the resetting response curve. Damped cycle length oscillation after a long return cycle during resetting was always present when there was a partially excitable gap.
Conclusions The reset window during pacing within the circuit and the maximum degree of advancement provided equally good estimates bracketing the shortest excitable gap. The slope of the resetting response curve predicted the likelihood of termination by premature stimuli. Damped cycle length oscillation after resetting detected a partially excitable gap.
Key Words: electrophysiology • tachycardia • reentry • pacing
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Introduction |
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The duration of the EG of a reentrant circuit and whether there is complete or incomplete recovery of excitability during the EG are important determinants of the behavior of reentrant arrhythmias.1 The duration of EG may help differentiate reentry around an anatomic barrier from reentry around functional lines of block.2 3 4 Incomplete recovery of excitability within the circuit may lead to CL oscillation that can spontaneously terminate reentry, whereas full recovery of excitability favors stable, sustained reentry.5 Antiarrhythmic drugs that lengthen refractoriness may terminate reentry only when the EG is short,6 7 8 9 whereas a long EG may facilitate entrainment of reentry by pacing.2 10 The ratio of the EG to tachycardia CL may predict the risk of pacing-induced acceleration due to double wave reentry.11 12 The slope of the resetting response correlates with the likelihood of terminating reentrant ventricular tachycardia with single premature stimuli.13
However, there has been confusion over the use of the term EG and difficulties in measuring it. Variations in the refractory period within the reentrant circuit produce variations in the EG during reentry.14 Resetting has been used to assess the EG in experimental and clinical models of reentry.1 15 16 17 18 19 20 The shape of the RRC can provide an indication of whether there is partial or complete recovery of excitability.1 17 20 The range of coupling intervals of premature stimuli that can reset a tachycardia is often presented as the EG of a reentrant circuit. It can provide a measure of the EG at one site when stimulation is applied within the circuit and premature stimuli do not terminate reentry.4 However, this is not necessarily the shortest EG within the circuit.
The shortest EG in the circuit occurs at the site with the longest ERP during reentry. Different tachycardias may have different shortest EGs. The shortest EG should be the most helpful measurement of EG for distinguishing between functional and anatomic barrier reentry. Functional barrier reentry may have a substantial EG in part of the circuit,2 but the shortest EG should be quite small. Therefore, if the shortest EG is large, then functional reentry is unlikely and the central barrier is probably anatomically defined. This is also the measure that determines the behavior and stability of an individual reentrant tachycardia and predicts whether prolongation of refractoriness will terminate reentry. A circuit with a large EG at one site may be terminated by prolongation of refractoriness if the shortest EG is sufficiently short. However, there are difficulties in measuring the shortest EG without recording from that site. Bernstein and Frame4 proposed methods to estimate the shortest EG in the circuit based on the amount of advancement of the tachycardia and the window of reset.
Resetting has several limitations for assessing clinical ventricular tachycardias. The resetting response cannot be interpreted when the tachycardia CL is variable. Moreover, resetting response cannot be performed in patients with hemodynamically unstable tachycardias.17 18 21 Easier alternative methods to characterize the EG would be very helpful.
In this study, we manipulated the duration of the EG during reentry in the atrial tricuspid ring model by the technique of adjustable reentry.22 By directly recording activation at multiple sites within the reentrant circuit, we were able to characterize the resetting response more thoroughly and accurately. We evaluated ways to estimate the shortest EG and explored the relationship between the slope of the RRC and the likelihood of termination of tachycardia by premature stimulation. We also validated a rapid method for detecting a partial EG.
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Methods |
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Twelve healthy mongrel dogs weighing 15 to 20 kg were anesthetized by pentobarbital 30 mg/kg IV. The heart was rapidly excised and immersed for dissection in cold Tyrode's solution equilibrated with 95% O2/5% CO2. The right atrial tricuspid ring preparation was dissected and mounted, endocardium upward, in a special tissue bath, as previously described.23
The Tyrode's solution contained (in mmol/L) NaCl 125, NaHCO3 24, NaHPO4 1.8, MgCl2 0.5, CaCl2 1.8, dextrose 5.5, and KCl 4.0. The solution was continuously bubbled with 95% O2/5% CO2 before entering the tissue bath and multiple sites around the circular chamber. In some experiments, a fixed concentration of acetylcholine between 1x10-9 and 3x10-7 mol/L was present.23 The temperature of the tissue bath was maintained at 34±0.1°C.
Electrical Recording
Activation sequences were recorded by 10 unipolar platinum electrodes spaced approximately equidistant in a circle around the ring. Electrograms were amplified with a bandwidth of 0.5 to 500 Hz (Bloom Associates). Signals were recorded on FM tape and on chart paper at 100 to 200 mm/s. Signals were also displayed on an eight-channel storage oscilloscope (model 5111, Tektronix). An Apple Macintosh II computer with custom software provided on-line display of CLs recorded from the site of block.
MAPs were recorded near the site at which unidirectional block and termination of reentry occurred. In the earlier two experiments, we recorded MAPs with 6F platinum quadripolar catheters. In later experiments, we used Ag-AgCl–tipped Franz MAP catheters (EP Technologies). APD was measured at 90% repolarization.
Adjustable Reentry Preparation
After an equilibration period, premature stimuli were delivered from several sites to determine the site with the longest ERP susceptible to block. A pacing electrode for initiating reentry was placed adjacent to this site. The ring was then cut 1 to 2 cm from the pacing electrode on the side opposite the unidirectional block site. Adjustable reentry was established by sensing activation on one side of the cut and pacing the other side after an adjustable electronic delay.22 Steps were taken to ensure that the electronic connection did not contribute to CL oscillation or termination of reentry, as previously described.9
Protocol
In each experiment, we reset tachycardias at 2 to 3 delays when tachycardia CLs were constant. Stimulation was performed through separated Teflon-coated bipolar silver wire electrodes placed between the recording electrodes controlled by a stimulator (Bloom Associates). Stimuli were 2 ms in duration and 3 times diastolic threshold current. Resetting premature impulses were introduced after every 12th reentrant cycle and decremented by 10 ms. Each coupling interval was repeated three times. If the tachycardia was terminated, it was reinduced and shorter PCIs were introduced until the ERP at the site of stimulus was reached.
Table 1
lists the definitions of parameters measured in this study. Resetting of reentry is defined as advancement of the tachycardia, ie, PCI+RC<2 reentry CLs. A resetting response curve described the relation of the PCI to the return cycle at the site of stimulation during reentry. The return cycle represents the conduction time of the premature impulse through the circuit in the orthodromic direction (including the electronic delay). Portions of the RRC were labeled as flat or increasing, depending on the changes in the return cycle, as the PCI was shortened. The criteria for defining the flat portions and increasing portions were those used previously by Bernstein and Frame.4 Full recovery of the EG was characterized by a flat portion of RRC at longer coupling intervals, whereas partial recovery of the EG was manifested by a purely increasing RRC. The PCI, the return cycle, and the degree of advancement were measured at the recording electrode nearest to the stimulus site in the orthodromic direction (<0.7 cm away). The maximum degree of advancement was the greatest advancement of tachycardia produced by any of the premature impulses that reset reentry.
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We measured ERPp and ERPb during reentry. The EG was calculated by subtracting ERP from the tachycardia CL. Thus, we measure a temporal EG, not a spatial EG. The shortest EG within the circuit is the site at which the latest premature impulse that terminated reentry will block. This is the site with the longest ERP at which spontaneous termination of reentry and unidirectional block occurs.9 In some experiments, we measured the local conduction curves across the site of the slowest conduction at different delays in the same preparation.
Statistical comparisons were made by paired two-tailed Student's t tests and unpaired t test, where appropriate. Values of P<.05 were considered significant. Summary data are expressed as mean±SD. The slope of the RRCs or local conduction curves near ERP was determined by simple linear regression over the shortest 40-ms range of coupling intervals. The relationship between ERP difference and slope of the RRC was also evaluated by simple linear regression.
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Results |
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Resetting Response Patterns
We performed resetting at 31 delays in 12 preparations. Two types of RRCs were seen. A mixed curve, with a flat portion indicating full recovery of excitability at long coupling intervals and an increasing portion at shorter intervals, was present in 15 of 31 delays. The other 16 of 31 delays had only an increasing portion of the RRC, which suggested partially excitable gaps during reentry. Data from resetting are shown in Table 2
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Tachycardias were terminated by premature stimuli in 16 delays in 8 of 12 experiments. The RRC had a mixed pattern in 12 and an increasing pattern in 4. In all cases, the coupling intervals of stimuli that terminated reentry were shorter than those that reset the tachycardia, so that one could determine a window of reset and a window of termination. The ERPb and the shortest EG can be precisely determined only when premature stimuli can terminate the tachycardia.
Estimating the Shortest Excitable Gap Within the Reentrant Circuit
Fig 1 shows the relationship between the shortest EG (at the site of block) and various parameters measured at the site of pacing during resetting that can be used to estimate the shortest EG. At a delay of 120 ms, the tachycardia CL was 301 ms (Fig 1A). A stimulus with PCI of 210 ms reset the tachycardia and produced a long return cycle of 321 ms. Therefore, the tachycardia was advanced by 71 ms [2x301-(210+321)=71 ms]. The longest PCI that terminated reentry was 180 ms (Fig 1B), so the window of reset was 121 ms (301-180=121 ms). However, ERPb defined by the coupling interval at site 6 was 200 ms. Thus, the shortest EG was 101 ms (301-200 ms). This value is between the window of reset (121 ms) and the maximum degree of advancement of 85 ms (not shown). The window of reset was longer than the shortest EG because of slower conduction of premature impulses before the site of block. The maximum degree of advancement during resetting is less than the shortest EG because of interval-dependent slowing of conduction at the site of block and distal to it. The ERPp defined by the longest coupling interval that failed to capture the tissue at the site of pacing was 125 ms (Fig 1C), so the EGp was 176 ms (301-125 ms).
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Table 3 illustrates the relationship between the shortest EG and the other parameters in all eight experiments for which ERPb and the shortest EG could be measured. The window of reset was 25±14 ms longer than the shortest EG, whereas the maximum degree of advancement was 22±11 ms shorter than the shortest EG. The total difference between these two estimates was 47±11 ms, which is equal to the change in the return CL over the window of reset. The shortest EG was closer to the window of reset if slower conduction of premature impulses occurred distal to the site of block but closer to the maximum advancement of tachycardia if the slower conduction occurred proximal to the site of block.
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Slope of RRCs in Relation to Termination by Premature Stimuli
Tachycardias terminated by single premature stimuli had significantly (P<.01) steeper slopes of the RRCs than those that were not terminated, as shown in Fig 2. The mean slope for tachycardias for the 16 delays terminated by premature stimuli was -0.69±0.2 versus -0.37±0.2 for the 15 delays not terminated. The slope was steeper than -0.55 in 12 of 16 delays (75%) in which tachycardias were terminated but only 2 of 15 delays (13%) in which tachycardias were not terminated.
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Reducing the delay increased the slope of the RRC in all experiments (see Table 2
). Fig 3 shows an example. The steepest slope of the RRC increased from -0.47 to -0.88 in steps when the delay was decreased from 220 to 120 ms in steps. Reducing the delay increased the termination window in the six experiments in which termination occurred at more than 1 delay. Decreasing the delay also led to termination by premature stimuli in five of the nine experiments in which termination did not occur at the longest delay.
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Despite these effects of reducing delay, there was no significant difference in the mean CL or EG at the pacing site in tachycardias terminated by premature stimuli versus those not terminated (Table 4). However, the mean ERPp was significantly shorter in those tachycardias terminated by premature stimuli than in those not terminated (172±30 versus 224±37 ms, P<.001). Therefore, the likelihood of termination of the tachycardia was also related to how early premature stimuli could activate the tissue.
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ERP Difference in Relation to the Slope of RRC and to the Ability to Terminate Reentry by Earlier Premature Stimuli
The relationship between the slope of the RRC and likelihood of termination may be related in part to changes in the ERP difference between the site of pacing and the site of block. In the six experiments in which both ERPp and ERPb could be measured at more than 1 delay, decreasing the delay increased the ERP difference because ERPp decreased more than ERPb (P<.01). A mean decrease in the delay of 40±12 ms resulted in a significant (P<.01) decrease of 13±7 ms in ERPp and significant (P<.01) increases in ERP difference of 10±5 ms. The decrease of 3.5±4 ms in ERPb was not significant.
The change in the ERP difference with delay can be seen in Fig 1. A 100-ms decrease in delay (from 220 ms in Fig 1D and 1E to 120 ms in 1A through 1C) produced a 20-ms decrease in ERPp (from 145 to 125 ms) but only a 2-ms decrease in ERPb (from 202 to 200 ms). This increased the ERP difference and allowed the premature stimuli to capture at the site of stimulation earlier relative to ERPb at delay 120 ms than during delay 220 ms. The termination window increased from 35 to 55 ms.
Fig 4 shows a direct relationship between the slope of the RRC and the ERP difference in the six experiments that could be terminated by premature stimuli at more than 1 delay. The correlation coefficient for the linear regression was .73 (P<.05).
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ERP) among 16 of 31 delays terminated by premature stimuli. Correlation coefficient was .73 (P<.05).
When reducing the delay resulted in termination of reentry by single stimuli and in a greater ERP difference, the earliest premature impulses encountered a steeper portion of the conduction curve at the critical site of block. Fig 5 compares the local conduction curves measured at the site of block for a longer delay at which only resetting was observed and for a shorter delay at which early premature stimuli terminated reentry. The slopes were -0.27 and -0.56. The corresponding slopes of the entire RRCs (see Table 2, experiment 7) were -0.54 and -0.92, respectively.
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, Data from delay 250 ms at which reentry was not terminated by premature stimulation; 
, data from delay 150 ms at which earlier premature stimuli terminated reentry.
Damped CL Oscillation After Resetting by a Premature Stimulus Predicts a Partially Excitable Gap
The presence or absence of CL oscillation after resetting differentiated circuits with a partially excitable gap from those with a fully excitable gap. CL was constant after the return cycle for the 15 delays with a fully excitable gap, whereas there was damped CL oscillation after the return cycle for the 16 delays that had incomplete recovery during a partially excitable gap. The two responses are contrasted in Figs 6 and 7. In Fig 6, with a delay of 125 ms, the RRC (top right) has a flat portion at long PCIs, indicating a fully excitable gap. The plot of consecutive CLs during resetting (top left) indicates that after premature impulses and long return cycles, the CL returned to the constant value of the native tachycardia. The electrograms at the bottom reveal that the reentrant impulse does not conduct faster after the long return cycle.
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Fig 7 shows the resetting response at a shorter delay from the same experiment that resulted in a partially excitable gap, as indicated by a strictly increasing RRC (Fig 7B). There was damped CL oscillation after each premature impulse that resets the tachycardia (Fig 7A). Recordings from the circuit show variations in CL and diastolic interval that cause variations in conduction for several cycles after the long return cycle (Fig 7C).
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Discussion |
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This study examines resetting responses in a model of reentry around an anatomic barrier that may be useful for predicting the likelihood of tachycardia termination by premature stimuli or antiarrhythmic drugs. We have verified the relationship between intervals measured during resetting and the duration of the shortest EG. We have confirmed a relationship between the slope of the RRC and the chance of terminating reentry by premature stimuli and reported observations that may explain this correlation. Finally, we have demonstrated that damped oscillation after resetting is a marker for a partially excitable gap.
Estimating the Duration of the Shortest Excitable Gap Within the Circuit
In many studies, the window of reset is used to characterize the EG of a reentrant circuit.1 16 18 24 The entire interval, including the reset window and termination window, measures the duration of the EG at the point in the circuit at the site of stimulus, if stimuli are delivered within the circuit. Therefore, if premature stimuli can terminate reentry, the window of reset by itself does not measure the local EG or reflect the EG at any point in the circuit. Heterogeneity of ERP in the reentrant circuit results in the different durations of the local EG around the circuit in anatomic or functional barrier reentry.14 25 During pacing from outside the circuit, the local EG may indicate nothing about the reentrant circuit because of the effects of intervening tissue between the pacing site and the circuit.
It is the shortest EG in the reentrant circuit that most strongly influences the behavior of the tachycardia and responses to antiarrhythmic drugs.14 Therefore, estimation of the shortest EG in the reentrant circuit is important for characterizing the reentrant circuit. Bernstein and Frame4 proposed that the window of reset obtained by pacing within the circuit provides an upper-limit estimate of the shortest EG and the maximum degree of advancement of the tachycardia provides a lower-limit estimate.
In this study, we quantitatively evaluated these estimates of the shortest EG. On average, the shortest EG was about halfway between the two estimates. However, the estimate that was closer varied, depending on the locations of pacing relative to regions of interval-dependent conduction slowing. The window of reset exceeded the shortest EG if early premature impulses conducted more slowly before reaching the site of block. The maximal degree of advancement was less than the shortest EG by the amount that premature impulses conducted more slowly beyond the site of block.
The difference between the two estimates is equal to the increase in the return CL over the window of reset. Thus, the difference between the two estimates tends to increase as either the slope of the RRC or the range of coupling intervals showing increasing return cycles increases. When there is a smaller increase in the return cycle, the estimate of the shortest EG is more accurate. If the curve is flat and the tachycardia cannot be terminated by single premature stimuli, then either pacing is being performed at the site with the shortest EG or the gap is uniform around the circuit. In that case, the window of reset and the maximal degree of advancement are the same and equal the shortest EG.
A possible caveat to these conclusions is that they may not hold if the site with the shortest EG is activated by the antidromic impulse during resetting. In this case, the site of the shortest EG is activated early by the antidromic impulse. It will recover earlier and thereby be partially protected from block. In this situation, the maximal degree of advancement may be greater than the shortest EG.
What is Meant by Excitable Gap?
References to the EG have frequently not distinguished between the shortest EG within the circuit and the EG at an arbitrary point in or outside the circuit during reentry. This has led to apparently conflicting data and conclusions. Variations in conduction velocity have been said to produce variations in the EG at different sites,26 but this conclusion refers to the calculations of the spatial EG, not the temporal EG. It has been stated that there is no EG in leading-circle reentry.27 Conversely, evidence of an interval of full repolarization in tissue away from the functional barrier has been cited as evidence for an EG during anisotropic reentry, even though no such interval of full repolarization is observed near the turning points around the barrier.28 Studies that record from the reentrant circuit can identify a local EG in functional barrier reentry even in the absence of resetting and advancement of the entire circuit.2 These apparent inconsistencies may be resolved if it is clear whether one is talking about the shortest EG or the EG at an arbitrary site. An EG in any part of the circuit may stabilize functional barrier reentry, but the shortest EG may best differentiate it from anatomic barrier reentry.
Relationship Between the Slope of the RRC and Termination by Premature Stimuli
In a study of 17 human ventricular tachycardias, Gottlieb et al13 found that the slope of the RRC in those tachycardias terminated by stimuli (-0.85±0.15) was significantly steeper than in those that did not terminate (-0.61±0.21). The slope that best separated those that did and did not terminate was -0.75. They hypothesized that regions with greater interval-dependent conduction may also have longer ERPs and predispose to conduction block.
The present study shows a remarkably similar correlation between slope and the likelihood of termination by premature stimuli. We found a similar separation between the two groups, although the slope that best separated them was slightly less (-0.55).
In both studies, there was no difference in the mean tachycardia CL between the two groups. One apparent discordance was that there was no significant difference in the prematurity of impulses that reset between the two groups in the above-mentioned clinical study, whereas we observed a shorter ERP at the stimulation site in those terminated by premature stimuli. However, they did not explore the termination window and were thus not measuring the entire EG at the site of pacing or the site of first interaction of premature impulses with the circuit.
Mechanism of the Relation Between Slope and Termination
Observations from this study help explain why a steep RRC indicates a better chance of terminating reentry by premature stimulation. In this preparation, the site with the greatest interval-dependent conduction usually has the longest ERP and is likely to be the site of block during spontaneous termination or with premature stimulation.9 These sites often demonstrate postrepolarization refractoriness. A steep RRC in some clinical tachycardias may indicate the presence of similar tissue likely to cause block at long coupling intervals.
In our study, termination was more likely at shorter delays, when the ERP difference was increased and the slope of the RRC was steeper. We considered two possible explanations for this finding: Greater ERP difference, which facilitates termination by stimuli, may directly contribute to the increase in slope because it allows earlier premature impulses to encounter the steepest part of the conduction curve at the site of block. Alternatively, the correlation may result from the fact that rate-dependent changes in the tissue properties are responsible for both the increase in ERP difference and the increased slope of the RRC. In either case, a steeper slope may be a marker for a greater ERP difference, which facilitates termination by premature stimuli.
Damped CL Oscillation After Resetting Indicates a Partially Excitable Gap
Frame et al23 proposed that either of two observations indicated incomplete recovery during the EG: a long return cycle after a very late premature impulse that barely reset the reentrant circuit or a shorter than normal cycle after a long return cycle. We previously demonstrated damped CL oscillation after resetting during reentry in the atrial tricuspid ring model in vitro with a partially excitable gap5 and no CL oscillation after resetting in a ventricular reentry model with a fully excitable gap.
In this study, the adjustable reentrant model allowed us to produce both a fully and a partially excitable gap during reentry in the same preparation by changing the delay. We found a complete concordance between the presence or absence of damped oscillation after resetting and the presence or absence of a partially excitable gap as indicated by a strictly increasing resetting response. Furthermore, this marker for a partially excitable gap was very robust. It was seen over the full range of PCIs that produced a long return cycle. Damped CL oscillation after resetting is a sensitive and specific marker that can quickly identify a partially excitable gap in a reentrant circuit without the need to complete a full RRC.
Limitations of This Study
In this study, we used two different methods for measuring ERP at the site of block and at the site of stimulation. ERPb was measured in terms of the coupling intervals of propagating premature impulses that blocked at this site. This method reflects all the factors, including excitability, cell coupling, and current load at the site of block, that determine whether premature impulses will block during reentry and terminate the tachycardia. We believe that this method leads to the most meaningful calculation of the shortest EG in the circuit. This definition of ERPb is analogous to the way in which refractory periods of the AV node or bypass tracts are measured in clinical electrophysiological studies.
However, this method can be used only to evaluate sites of relatively long refractoriness at which early impulses that activate nearby tissue will block. At the site of stimulation, we used a conventional stimulus method. As a result, the difference between ERPb and ERPp reflects different methods of measuring ERP. We do not think that this represents a significant problem for interpreting the results, for three reasons. First, the methods we used are relevant to understanding how early premature stimuli can terminate reentry. ERPp indicates the timing of stimuli that can activate the tissue, and ERPb indicates how early an impulse must be to terminate the tachycardia. Second, our analysis focused on the changes in ERP difference as delay was decreased. We expect that changes in the stimulus strength would have altered each measurement of ERP difference by a similar amount, so that the change in this parameter would be unaffected. Finally, decreasing the electronic delay increased both the ERP difference and the termination window in similar amounts (see Table 2). Both ends of the termination window are determined by use of coupling intervals of stimuli, so that changes in the window cannot be attributed to different methods of measurement. This suggests that the changes in ERP difference were real and meaningful for termination of reentry.
One important difference between resetting in this study and in clinical tachycardias is that resetting of clinical tachycardias is usually performed from outside the reentrant circuit. The earliest coupling interval in the window of reset may be limited by the refractory period at the site of pacing rather than refractory periods within the circuit. Thus, the window of reset from outside the circuit may not be longer than the shortest EG in the circuit. The use of double premature stimuli can reveal the window of reset more completely.17 21 The maximal degree of advancement should provide a useful estimate even during pacing outside the circuit.
The damped oscillations of CL in our model were 10 to 20 ms, whereas tachycardia CLs at the delays studied varied by 
1 ms. In clinical tachycardias, if the precision of measurement is lower or if there is more baseline variation, it may be more difficult to determine whether the CL oscillation after resetting is significantly increased.
Relevance of the Model
The canine tricuspid ring model in vitro shares important properties with certain clinical reentrant circuits. A long relative refractory period with marked interval-dependent conduction is characteristic of tissue supporting ventricular tachycardia due to ischemia or infarction in humans.18 Both increasing and mixed resetting responses are observed in human ventricular tachycardia.18 21 The steeper slope of RRC was also associated with an increased likelihood of tachycardia termination by premature stimuli in human ventricular tachycardia.13 Examples of damped oscillation after resetting of clinical ventricular tachycardia have been published.29 These observations suggest that the reentrant circuits in our model and in humans share important properties, although important differences exist.
Clinical Implications
These results have implications for predicting termination of clinical tachycardias by premature stimulation or pacing. Our data reinforce the relationship between a steep slope of the RRC and termination by premature stimulation identified by Gottlieb et al.13 Furthermore, we observed rate-dependent enhancement of termination by premature stimuli along with increased ERP difference, which suggests that premature stimulation during rapid entrainment of tachycardia may be more effective than when delivered alone during a tachycardia. A combination method of pacing involving entrainment at CLs 10 to 100 ms less than the tachycardia CL followed by one or more premature stimuli was found to be more effective in terminating human ventricular tachycardia than premature stimuli alone.30 Its success was attributed to reversing the activation sequence between the pacing site and the circuit so that premature impulses could reach the circuit within the EG. Our data suggest that the period of entrainment may also make the reentrant circuit more susceptible to termination.
The working group that developed the Sicilian Gambit has proposed that a short EG is a vulnerable parameter for a reentrant circuit to be terminated by drugs that prolong refractoriness.6 The present study suggests that it would be more meaningful to state that the shortest EG will predict which tachycardias will be terminated. The window of reset may not be the same as the shortest EG.
Finally, for patients who are hemodynamically too unstable to tolerate a full resetting protocol, damped oscillations after a single premature stimulus that reset the tachycardia may be sufficient to indicate a partially excitable gap. This observation may indicate that the gap may be short enough to be closed by a class III drug.
Extrapolation of conclusions from a simple in vitro model to the complex substrate of clinical arrhythmias should be circumspect. Our experimental study should be viewed as suggesting hypotheses that require further validation in human beings.
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Acknowledgments |
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This study was supported by grant HL-38386 from the National Heart, Lung, and Blood Institute, Bethesda, Md.
Received April 1, 1996; revision received May 23, 1996; accepted May 27, 1996.
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References |
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Gottlieb CD, Rosenthal ME, Stamato NJ, Miller JM, Lesh MD, Frame LH, Josephson ME. A quantitative evaluation of refractoriness within a reentrant circuit during ventricular tachycardia: relationship to termination. Circulation. 1990;82:1289-1295.
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