Rapid Rates During Bradycardia Prolong Ventricular Refractoriness and Facilitate Ventricular Tachycardia Induction With Cesium in Dogs
Background Bradycardia can promote the development of some ventricular tachycardias (VTs). We investigated whether relative bradycardia per se or the transition from a rapid to a slower ventricular rate might be important in developing VT.
Methods and Results We studied groups of anesthetized closed-chest dogs that had AV block produced by radiofrequency catheter ablation of the AV junction. One group had uninterrupted AV block; the other group underwent a period of rapid left ventricular pacing. Both groups then received incremental doses of CsCl until sustained VT resulted. We also measured ventricular effective refractory period (V-ERP) and QT interval in separate groups of dogs that had AV block for 1 week or 3 days with and without rapid pacing (pacing cycle length [PCL]=500 or 250 ms) for 1 hour or 30 minutes. Finally, we investigated the effects of rapid pacing on V-ERP by testing the effects of verapamil and autonomic denervation on these changes. We found that CsCl induced larger early afterdepolarizations and a greater prevalence of VT in dogs with rapid pacing than in dogs without. In dogs that had AV block for 1 week, 1 hour of rapid pacing prolonged V-ERP and QT interval compared with V-ERP and QT interval before pacing. Changes persisted for at least 3 hours. Rapid pacing for only 30 minutes and at a PCL of 250 ms, as well as superimposition on sinus rhythm, each prolonged V-ERP but to a lesser extent. Only 3 days of complete AV block and autonomic denervation did not affect the prolongation of V-ERP produced by rapid pacing, whereas verapamil significantly blunted but did not eliminate the prolongation.
Conclusions At the same PCLs, the heart exposed to transient tachycardia superimposed on bradycardia exhibited a longer V-ERP, QT interval, and monophasic action potential duration and greater ease for developing VT than the heart exposed only to bradycardia. The prolongation of refractoriness lasted for at least 3 hours, and the Δ-ERP was influenced by the heart rate before pacing, the duration of pacing, and the PCL. The mechanism for this response to rapid rates appears to involve calcium, at least in part.
Bradycardia influences the induction of EADs1 2 3 that might be the basis of torsade de pointes due to drugs such as quinidine. Some data suggest that patients with atrial fibrillation are more likely to develop torsade de pointes when they con-vert to sinus rhythm and are most likely to have a slower rate.4 Torsade de pointes has also been reported after sudden precipitation of complete AV block due to radiofrequency catheter ablation.5 These responses raise the question of whether the acute onset of bradycardia after a period of tachycardia facilitates the induction of torsade de pointes, perhaps by prolonging repolarization. The purpose of this study was to test whether an intervening period of a rapid heart rate during a bradycardia influenced the ability of CsCl, a potassium channel blocker, to induce torsade de pointes6 7 8 9 10 11 12 13 14 15 and whether such rate manipulations affected refractoriness.
Fifty-three mongrel dogs of both sexes weighing 20 to 30 kg were anesthetized with sodium pentobarbital (30 mg/kg IV). Additional doses were given as necessary to maintain anesthesia during the study. The dogs were artificially ventilated with room air by a constant-cycled-volume ventilator (model 607, Harvard Apparatus). Catheters were placed in the left femoral artery and vein to monitor arterial BP and to infuse drugs. A 6F electrode catheter (EP Technologies) was introduced into the AV junction via the right femoral vein, and radiofrequency energy was delivered between the tip of the catheter and a backplate to produce complete AV block. MAPs were recorded via a 6F contact electrode catheter (EP Technologies).16 The electrode catheter was introduced into the left common carotid artery through a 7F sheath, and the tip was positioned at the apical endocardial portion of the LV. The signals were amplified and filtered at a frequency range of 0.04 to 500 Hz. MAPs were recorded simultaneously with surface ECG leads I, II, and III.
EADs were defined as an interruption in the smooth contour during phase 3 repolarization of MAPs. The magnitude of the EADs was calculated by a method that measured the area of the MAP and EAD. Lines were drawn to extend the smooth portion of phase 3 of the MAP and along the resting potential until they intersected. The area enclosed by these two lines separated the EAD from the MAP. The area of the EAD was expressed as a percentage of the total MAP area. We have shown previously that this method correlated accurately with the amplitude of EADs expressed as a percentage of the MAP amplitude.11 12 13 MAPD90 was measured simultaneously with measurement of EADs.
The QT interval was measured from the surface ECG lead II during constant LV pacing before the injection of CsCl and every 1 minute after the injection of CsCl for 5 minutes. The QT interval was defined as the interval between the earliest onset of the QRS complex and the point at which the line of maximal downslope of the T wave crossed the baseline.
The ERP at the LV apex was determined by the extrastimulus method with a programmable stimulator (Krannert Medical Engineering), as we have reported previously.17 The stimulus was a 2-ms rectangular pulse at twice diastolic threshold. A train of eight stimuli (S1) was followed by a late extrastimulus (S2) that produced a ventricular response. BCLs of 500, 700, 800, and 1000 ms were used, and the coupling interval (S1S2 interval) was shortened in steps of 10 ms until S2 failed to produce a ventricular response. Then the S1S2 interval was increased by 10 ms and shortened by 1-ms decrements until S2 failed to capture the LV. The ERP of the LV was defined as the longest S1S2 interval at which S2 failed to capture the LV. The measurement of ERP was repeated three times.
Induction of VT
The purpose of this protocol was to determine dose-response curves for CsCl induction of VT in dogs with complete heart block compared with dogs that had complete heart block interrupted by a period of rapid pacing.
The LV was paced at a PCL of 1000 ms during the injection of CsCl. Pacing was discontinued when spontaneous ventricular arrhythmias occurred. CsCl was injected intravenously over 20 seconds at incremental doses (0.25, 0.5, 0.625, 0.75, and 1.0 mmol·L−1·kg−1) spaced at intervals of 30 minutes to determine the dose required to induce sustained VT. MAPs were recorded from the LV endocardium within 5 minutes of the completion of the CsCl injection when the maximal effect of the drug occurred. The area of MAPs and EADs was determined as the average of three consecutive ventricular paced complexes. The QT interval was measured from the same complexes from which EAD values were measured. Recordings were stored on an analog tape throughout the experiment, digitized by a analog-to-digital converter, and played back on the monitor of a personal computer to analyze data.
Dogs with AV block for 1 week that did not have intervening rapid ventricular pacing before the injection of CsCl (Fig 1A⇓)
This protocol tested the effects of bradycardia alone on VT induction.
In a group of 8 dogs that had complete AV block for 1 week, CsCl was injected during constant LV pacing at a PCL of 1000 ms. Doses beginning with 0.25 mmol·L−1·kg−1 were increased incrementally until sustained VT was induced. The dose of CsCl that induced sustained VT was the end point of this experiment.
Dogs with AV block for 1 week that had intervening rapid ventricular pacing for 1 hour immediately before the injection of CsCl (Fig 1A⇑)
This protocol tested the effects on VT induction of a rapid heart rate superimposed on the bradycardia.
In a separate group of 7 dogs that had complete AV block for 1 week, rapid LV pacing (PCL=500 ms) for 1 hour was introduced immediately before the injection of CsCl. CsCl was injected during constant LV pacing after PCL returned to 1000 ms, as described for the dogs that did not have intervening rapid pacing.
V-ERP Before and After Rapid Ventricular Pacing for 1 Hour in Dogs With AV Block for 3 or 7 Days
The purpose of this series of protocols was to test the influence on V-ERP of the duration and rate of the superimposed rapid pacing, the duration and rate of the rhythm before rapid pacing, and the influence of verapamil and of autonomic manipulation.
V-ERP in dogs that had complete AV block for 1 week and underwent 1 hour of rapid pacing at a PCL of 500 ms (Fig 1B⇑)
This protocol tested the effects on V-ERP of bradycardia alone and bradycardia with a superimposed rapid rate.
In 6 dogs that had complete AV block for 1 week, V-ERP was measured at several PCLs (500, 700, 800, and 1000 ms) before and immediately after 1 hour of pacing at a PCL of 500 ms. As a sham control, V-ERP was measured at a PCL of 1000 ms after a 1-hour interval in a separate group of 5 dogs that had complete AV block for 1 week but did not undergo rapid pacing (Fig 1B⇑). In this sham control group, to exclude the effect on V-ERP of PCLs shorter than 1000 ms during S1S1 beats, only a PCL of 1000 ms was used.
Time course of V-ERP
This protocol tested the duration of the V-ERP produced by rapid pacing.
V-ERP was followed for 3 hours at 1-hour intervals in a separate group of 3 dogs that had complete AV block for 1 week and underwent rapid pacing (PCL=500 ms) for 1 hour.
V-ERP in dogs that had complete AV block for 1 week with 30 minutes of rapid pacing
This protocol tested the influence on V-ERP of the duration of rapid pacing superimposed on a bradycardia.
In a separate group of 6 dogs that had complete AV block for 1 week, V-ERP was measured before and immediately after 30 minutes of rapid pacing at a PCL of 500 ms in the same fashion as dogs that had 1 hour of pacing.
Dogs with sinus rhythm that received 1 hour of rapid pacing at a PCL of 250 ms
This protocol tested the influence on V-ERP of the cycle length before the superimposition of rapid pacing.
To estimate the influence of heart rate before pacing on these results, V-ERP was measured at several PCLs (250, 300, 350, and 400 ms) before and after 1 hour of rapid pacing at a PCL of 250 ms in 5 dogs that had a normal heart rate (CL=441±56.2 ms).
V-ERP in dogs that had complete AV block for 1 week with 1 hour of rapid pacing at a PCL of 250 ms
This protocol tested the influence on V-ERP of the cycle length of rapid pacing superimposed on a bradycardia.
V-ERP was measured in 3 dogs that had complete AV block for 1 week and received very rapid pacing at a PCL of 250 ms to estimate the effect of PCL on V-ERP.
V-ERP in dogs that had complete AV block for 3 days and rapid pacing for 1 hour
This protocol tested the influence on V-ERP of the duration of bradycardia before superimposed rapid pacing.
V-ERP was measured in 3 dogs that had complete AV block for 3 days after 1 hour of rapid ventricular pacing at a PCL of 500 ms in the same fashion as in dogs that had 1 week of AV block.
V-ERP in dogs with 1 week of complete AV block that received verapamil administration before and during rapid ventricular pacing at a PCL of 500 ms for 1 hour
This protocol tested the influence of verapamil on V-ERP prolongation produced by rapid pacing.
V-ERP was measured in 3 dogs that had 1 week of complete AV block. In this group, after control V-ERP was measured, a loading dose of verapamil (0.015 mg·kg−1·min−1 IV) was administered for 5 minutes, and a maintenance dose (0.003 mg·kg−1·min−1 IV) was infused for 2 hours, beginning 60 minutes before and continuing during rapid ventricular pacing.
V-ERP in dogs with 1 week of complete AV block that had vagal and sympathetic denervation before rapid ventricular pacing at a PCL of 500 ms for 1 hour
This protocol tested the influence of autonomic manipulation on V-ERP prolongation produced by rapid pacing.
V-ERP was measured in 3 dogs that had 1 week of complete AV block and 1 hour of rapid ventricular pacing at a PCL of 500 ms after surgical interruption of the right and left vagus nerves in the neck and both ansae subclaviae in the chest.
Definition of the VTs
The following definitions were used in this study.
1. Nonsustained VT was defined as three or more consecutive premature ventricular complexes terminating spontaneously within 30 seconds.
2. Sustained VT was defined as VT lasting more than 30 seconds. If the dog developed short bursts of an incessant VT, it was counted as sustained VT when more than half of a 2-minute period after the injection of CsCl was spent in VT.
3. Torsade de pointes was defined as polymorphic VT during which the QRS complex twisted around the baseline, lasting more than six consecutive beats.
4. Ventricular fibrillation was defined as disorganized, irregular ventricular complexes with changing contours, resulting in the absence of systemic arterial BP.
Data were expressed as mean±SD. Differences of %EAD, QT interval, MAP duration, and V-ERP were analyzed by two-way ANOVA and paired or unpaired t test. If an ANOVA was significant, the Newman-Keuls test was used to determine difference. The frequency of ventricular arrhythmias was analyzed by χ2 test. A value of P<.05 was considered statistically significant.
Response of Dogs With and Without Rapid Pacing to CsCl
During 1 week of AV block, the ventricular escape cycle lengths were similar in dogs that underwent rapid pacing (1209±111 ms) and dogs that did not undergo rapid pacing (1216±116 ms) (P=NS).
The %EAD was greater in the dogs with 1 hour of rapid pacing than in the dogs without rapid pacing at each dose of CsCl except 0.25 mmol·L−1·kg−1 (Table 1⇓). The dose-response curve of %EAD to CsCl for the dogs that did not receive rapid pacing was shifted downward and rightward compared with the dogs that did receive rapid pacing (Fig 2A, 2B, and 2C⇓⇓⇓).
QT Interval and MAP Duration
The QT interval and MAPD90 were longer in control and at each dose of CsCl except for 0.25 mmol·L−1·kg−1 in dogs subjected to 1 hour of rapid pacing compared with the dogs that did not receive rapid pacing (Table 1⇑, Fig 3⇓).
Bigeminy occurred at low doses of CsCl. As the dose of CsCl was increased, nonsustained VT or torsade de pointes was triggered and maintained by EADs that reached a sufficient magnitude (Fig 4⇓). A greater prevalence of ventricular arrhythmias was induced at the same dose of CsCl in dogs that underwent rapid pacing compared with the dogs that did not undergo rapid pacing (Fig 5⇓). The prevalence of sustained VT at 0.75 mmol·L−1·kg−1 of CsCl was greater in the dogs that had rapid pacing than in the dogs without rapid pacing (P<.05). Torsade de pointes was induced in 3 of 8 dogs that did not receive rapid pacing and in 6 of 7 dogs that had rapid pacing (38% versus 86%; P=.08).
Comparison of V-ERP Before and After 1 Hour of Rapid Pacing
V-ERPs in dogs that had complete AV block for 1 week and underwent 1 hour of rapid pacing
V-ERPs before and after 1 hour of rapid pacing at a PCL of 500 ms are shown in Table 2⇓ and Fig 6⇓. V-ERPs were prolonged after rapid pacing compared with before pacing at each BCL (P<.01). The QT interval (BCL=1000 ms) was 399±26 ms after and 380±24 ms before rapid pacing (P<.01). In the sham control group that did not undergo rapid pacing, V-ERP at the start of the hour was 249±21.3 ms, and it was 253±24.0 ms (P=NS; BCL=1000 ms) 60 minutes later. The QT interval was 360±9.0 ms at the start of the hour and 361±7.6 ms at 60 minutes (P=NS). The difference in V-ERP at a BCL of 1000 ms after 1 hour in dogs that had rapid pacing (36.3±9.5 ms) compared with dogs that did not have rapid pacing (4.2±4.7 ms) was significant (P<.01) (Table 2⇓). During rapid pacing at a PCL of 500 ms, mean arterial BP increased to 102±11.9 mm Hg compared with 97±13.1 mm Hg at a PCL of 1000 ms (P<.05). These changes of BP are statistically significant but of doubtful physiological importance.
V-ERPs in dogs that had complete AV block for 1 week and underwent 30 minutes of rapid pacing
V-ERPs after rapid pacing were prolonged compared with before pacing at each BCL (P<.01) (Table 2⇑). However, the increase in V-ERP was less than in dogs that underwent 1 hour of rapid pacing at each BCL (P<.01) (Table 2⇑, Fig 7⇓).
V-ERPs in dogs that had complete AV block for 1 week and underwent 1 hour of very rapid pacing (PCL=250 ms)
V-ERPs after 1 hour of pacing at a PCL of 250 ms were prolonged slightly compared with before pacing at each BCL, but the Δ-ERP was 6.7±1.5 ms, which was smaller than that at a PCL of 500 ms. During very rapid pacing, mean femoral BP was 92±4.6 mm Hg compared with 95±4.6 mm Hg before rapid pacing (P=NS).
V-ERP in dogs that had sinus rhythm and underwent rapid ventricular pacing for 1 hour
In dogs with normal heart rates (CL=441±56 ms), V-ERPs after pacing at each BCL were prolonged compared with before pacing (P<.05), but QT and QTc did not change (Table 3⇓). During rapid pacing, mean arterial BP decreased to 63±13.7 mm Hg compared with that during a normal heart rate (92±12.3 mm Hg; P<.05). The Δ-ERP was prolonged more in dogs that had AV block for 1 week and had 1 hour of rapid pacing (PCL=500 ms) than it was in dogs that had normal heart rates with 1 hour of very rapid pacing (PCL=250 ms). The Δ-ERP in dogs with normal sinus rhythm that received rapid pacing (PCL=250 ms) was slightly but not significantly greater at each BCL compared with that in dogs with 1 week of AV block that received rapid pacing (PCL=250 ms) for 1 hour.
Duration of prolongation of V-ERP produced by 1 hour of rapid pacing
The effect of rapid pacing (PCL=500 ms) for 1 hour continued for at least 3 hours. The V-ERP increase was 26.3±5.7 ms at 1 hour after pacing, 28.7±9.3 ms at 2 hours, and 31.7±5.5 ms at 3 hours. These values were not statistically different from the value immediately after pacing (28.7±2.2 ms).
V-ERP in dogs that had AV block for 3 days and underwent 1 hour of rapid pacing at a PCL of 500 ms
V-ERP was prolonged after rapid pacing (PCL=500 ms) compared with before pacing (P<.01, n=3) (Table 2⇑). There was no difference between Δ-ERP in dogs with 1 week of AV block that underwent rapid pacing for 1 hour compared with dogs that had 3 days of AV block and received rapid pacing for 1 hour (Fig 8⇓, Table 2⇑).
V-ERP in dogs that had 1 week of AV block and received verapamil administration before and during rapid ventricular pacing
V-ERP in dogs that had complete AV block for 1 week and had vagal and sympathetic neural denervation just before rapid ventricular pacing at a PCL of 500 ms for 1 hour
V-ERP was prolonged after rapid ventricular pacing compared with that before rapid pacing. Δ-ERP in the dogs with denervated AV block was not significantly different from that in dogs with innervated AV block (Fig 8⇑, Table 3⇑).
The main findings of the present study were that 1 hour of rapid pacing superimposed on AV block facilitated the induction of VT, including torsade de pointes, by CsCl. This response is probably related to the fact that V-ERP, QT interval, and MAP duration after rapid pacing were markedly prolonged compared with before pacing. Such prolongation of refractoriness lasted for at least 3 hours and was influenced by the heart rate before rapid ventricular pacing, the duration of the rapid pacing, and the CL of rapid pacing. Verapamil reduced but did not eliminate the pacing-induced ERP prolongation, and vagal and sympathetic neural interruption had no effect.
It has been well established that fast heart rates remodel the myocardium. Tachycardia-induced cardiomyopathy of the ventricles is now a recognized clinical entity that has been studied in a number of animal models.18 19 20 Recent data indicate that rapid rates can also lead to remodeling of the atrial myocardium, making it capable of sustaining atrial fibrillation.21 22
In the present study, we were interested in investigating whether slow heart rates also had a remodeling action that could influence the excitable properties of the heart. To that end, we created AV heart block that resulted in ventricular rates of about 50 bpm. We allowed the dog to remain in this state for 3 or 7 days. On this bradycardia, we superimposed a fast heart rate, thinking that the period of bradycardia would remodel the ventricle into having a very long refractory period that the tachycardia would then shorten. To our surprise, we found that after a period of rapid pacing, the ventricular refractory period was actually prolonged. This prolongation of refractoriness facilitated the induction of ventricular tachyarrhythmias due to EADs. It is of interest that pacing at a cycle length of 500 ms lengthened refractoriness more than it did at a cycle length of 250 ms. Furthermore, prolongation of the refractory period lasted at least 3 hours. The increase in LV refractoriness was paralleled by lengthening of ventricular repolarization, as indicated by prolongation of MAP duration and QT interval.
Although we did not determine the exact mechanisms explaining this prolongation of refractoriness and facilitation for induction of VT from these initial observations, we can narrow the spectrum of possible explanations.
Theoretically, any event that results in a net increase in intracellular positivity during repolarization, by decreasing outward repolarizing currents, increasing inward depolarizing currents, or both, is capable of prolonging action potential duration and refractoriness and, ultimately, generating EADs.7 8 9 10 11 12 13 14 15 23
The observation that verapamil attenuated the pacing-induced conditioning effect points to calcium as the possible mediator linking prolongation of LV refractoriness to rapid pacing. A gradual increase in stimulation frequency causes incremental increases in steady-state muscle inotropy24 (positive staircase effect), presumably as a result of voltage- and frequency-dependent potentiation of L-type Ca2+ current,25 26 which in turn augments calcium release from the sarcoplasmic reticulum stores during the action potential.27 This results in an increased Ca2+ transient and hence an increase in contractile force. Thus, with increased stimulation rate, the fraction of time intracellular calcium concentration exceeds the resting level increases significantly with stimulation frequency. Interestingly, switching from a low to a high stimulation rate can increase diastolic intracellular Ca2+ nearly fivefold in the intact heart.28
Another possibility is that elevated intracellular Ca2+ concentration could activate phospholipase C, which in turn could activate membrane-bound PKC, ultimately leading to phosphorylation of ion channels/ion pumps. For example, PKC-dependent phosphorylation inactivates the Ca2+-insensitive Ito1, the Na/Ca exchange current,29 and the Na/K pump, resulting in an overall increase in inward current during the action potential. On the other hand, PKC has been shown to activate a time- and voltage-dependent chloride channel in cardiac myocytes that in turn would result in an increase in repolarizing outward current. The final effect of PKC activation, of course, would depend entirely on the degree to which various channels/pumps are activated/inactivated by this protein.
The fact that surgical interruption of the vagus and sympathetic nerves had no effect on V-ERP prolongation would tend to exclude neural influences.
Significantly, the prolongation of refractoriness lasted at least 3 hours, suggesting that whatever was responsible for the change in ionic conductances was a relatively long-lasting event, such as phosphorylation of a channel protein. The event was influenced by the rate and duration of pacing as well as by the heart rate before pacing. Of the three causes of T-wave changes postulated by Katz,30 including structural alterations, metabolic changes in the cell, and changes in the proteins that regulate the potassium and other channels, the latter appears to be most likely.
Verapamil in our study surprisingly prolonged V-ERP before rapid pacing in dogs that had 1 week of AV block, with the effects being more pronounced at longer cycle lengths. The verapamil-induced lengthening of LV refractoriness is at variance with previous studies showing no effect of this compound on this parameter.31 This discrepancy can be explained by the transient increases in L-type Ca2+ channel current known to occur in cat papillary muscle and guinea pig ventricular myocytes32 ; modification of the channel's response to phenylalkylamine-type Ca2+ channel blockers, possibly because long-term bradycardia, by an unknown mechanism, enhances the stimulatory effect of phenylalkylamine blockers (dual action of Ca2+ channel blockers); or a verapamil-induced decrease in mean arterial BP, causing a reflex increase in sympathetic tone that might modulate currents contributing to the repolarization of cardiac action potential (eg, inactivation of the repolarizing Ito1 by α1-receptor activation of PKC), thereby prolonging repolarization.
The phenomenon we describe here appears to occur clinically. For example, when patients receiving quinidine for atrial fibrillation develop torsade de pointes, they do so usually after the atrial fibrillation converts to sinus rhythm, presumably associated with a sudden rate decrease.4 Also, the development of polymorphous ventricular tachycardia has been documented after the sudden creation of complete AV block with radiofrequency catheter ablation and is sometimes treated with rapid pacing.5 In each instance, the sudden onset of bradycardia after a tachycardia could be associated with prolongation of refractoriness and the risk of ventricular tachyarrhythmias. These examples are somewhat different from our animal model in that they did not first have a period of bradycardia. But in the present study, we also show that similar although quantitatively fewer increases in refractoriness can occur after a period of rapid pacing is superimposed on normal sinus rhythm. It is also possible that what we have shown is similar to what has been found on a beat-to-beat basis, such as during long-cycle/short-cycle sequences.33 34
Despite a very involved study, we have not actually demonstrated the mechanism responsible for the prolongation of the refractory period but rather merely pointed with suspicion to the role of calcium. We have not investigated the influence of stretch in this model. Several reports suggest that ventricular dilation might activate a stretch channel that could prolong refractoriness and generate afterdepolarizations.35 36 37 38 Other data suggest that acute ventricular dilation shortens refractoriness.39 40 41 42 Ultimately, the ionic mechanism responsible for the prolongation of refractoriness probably awaits exploration with voltage clamp and patch cell preparations.
This study was supported in part by the Herman C. Krannert Fund, Indianapolis, Ind, and grant HL-52323-01 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. We thank Michael Rubart, MD, for helpful discussions and Naomi S. Fineberg, PhD, for statistical analysis.
Selected Abbreviations and Acronyms
|BCL||=||basic cycle length|
|%EAD||=||area of MAP occupied by EAD|
|ERP||=||effective refractory period|
|Δ-ERP||=||change in ERP|
|LV||=||left ventricle, ventricular|
|MAP||=||monophasic action potential|
|MAPD90||=||MAP duration at 90% repolarization|
|PCL||=||pacing cycle length|
|PKC||=||protein kinase C|
- Received July 26, 1995.
- Revision received January 11, 1996.
- Accepted January 22, 1996.
- Copyright © 1996 by American Heart Association
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