Published online before print November 8, 2004, doi: 10.1161/01.CIR.0000147618.93579.56
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(Circulation. 2004;110:3161-3167.)
© 2004 American Heart Association, Inc.
Arrhythmia/Electrophysiology |
Restitution Properties During Ventricular Fibrillation in the In Situ Swine Heart
From the Cardiac Rhythm Management Laboratory, Division of Cardiovascular Disease, Department of Medicine (J.H., R.E.I.), Department of Physiology (R.E.I.), and Department of Biomedical Engineering (W.M.S., R.E.I.), University of Alabama at Birmingham, and Tachyarrhythmia Research, Medtronic Inc, Minneapolis, Minn (X.Z.).
Correspondence to Jian Huang, MD, PhD, Cardiac Rhythm Management Laboratory, Volker Hall B140, 1530 3rd Ave S, Birmingham, AL 35294-0019. E-mail jh{at}crml.uab.edu
Received January 22, 2004; de novo received April 26, 2004; accepted June 4, 2004.
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Abstract |
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Background— Although restitution has been hypothesized to determine action potential duration (APD) during ventricular fibrillation (VF), cardiac memory may also be important.
Methods and Results— Transmembrane recordings were made with a floating microelectrode from the anterior right ventricular wall in 6 pigs during up to 60 seconds of VF. The recordings were divided into 5-second intervals, and APD60 and the diastolic interval (DI) were calculated for each activation cycle throughout each interval. Stepwise linear regression was used to determine how well each APD60 [APD60(n)] was predicted by the 4 previous DIs (n–1, n–2, n–3, n–4) and the 3 previous APD60s (n–1, n–2, n–3). A mean±SD of 3±1.5 of the variables entered the regression equation. DI(n–1) (70% of intervals) and APD60(n–1) (71% of intervals) appeared most frequently in the regression equations and were the first or second variables entered during the stepwise regression in 87% and 76% of the intervals in which they were present, respectively. The coefficients of DI(n–1) and APD60(n–1) were positive 89% and 98% of the time, respectively. R2 of the regression for all entered variables during all intervals was 0.39±0.05.
Conclusions— The high incidence and positive coefficient of DI(n–1) indicate that restitution is important in determining APD during VF, whereas the similarly high incidence and positive coefficient of APD(n–1) indicate that cardiac memory is equally important. The finding that the regression equation accounts for only 39% of the variability of APD indicates that factors other than restitution and memory are also important in determining APD during VF.
Key Words: fibrillation • electrophysiology • arrhythmia
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Introduction |
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Whether it consists of multiple wandering wavelets1 or a single stable mother rotor that generates many daughter waves,2 reentry is generally agreed to be the engine that drives ventricular fibrillation (VF). For many years, it was believed that a preexisting anatomic or functional heterogeneity of refractoriness or conduction was the key factor for reentry formation.1,3,4 However, recent studies have illustrated that wave breaks can occur in tissue the properties of which are totally homogeneous.5,6 During VF, certain kinds of instability create heterogeneity, and restitution of the action potential duration (APD) is thought to be primarily responsible for this instability.7 In models of excitable media, alternans in APD and/or cycle length have been shown to be a precursor to block,8–10 and reentrant spiral waves have been shown to become unstable and break into multiple spiral waves when the slope of the restitution curve for refractoriness is >1.11
These mechanisms involve the dependence of APD on the previous diastolic interval (DI). In general, a long DI leads to a long APD and vice versa.12,13 If the slope of this restitution relationship is >1, then a small change in DI leads to a greater change in APD, which leads to a greater change in DI, etc, until block occurs. Many simulation and experimental studies have demonstrated that arrhythmias are more easily induced when the slope of the restitution curve is >114,15 and that drugs that flatten the curve can prevent arrhythmias.16,17 However, in most of these studies, the restitution curves were determined not during VF but rather after pacing for up to 50 cycles at a constant S1–S1 interval. This long string of constant cycle lengths removes any effects of short-term cardiac memory associated with variations in cycle length such as occur during VF.18 Cardiac memory is the phenomenon in which not just the previous DI but also the previous APD, as well as the DIs and APDs of even earlier cycles, influence APD.19,20 In addition to restitution, cardiac memory may also be important during VF.
Only a few studies have observed restitution properties during VF in the perfused heart, and these studies included small, brief deflections that may not represent true action potentials.14,21,22 In addition, these studies were performed in isolated, perfused hearts or portions of hearts in which electrophysiological properties may differ from those in intact in vivo hearts.23 In the present study, we performed microelectrode recordings from the epicardium of the intact heart in vivo to investigate the hypothesis that an APD restitution curve with a slope >1 is present during VF. We also evaluated the roles of restitution and cardiac memory in determining APD during VF.
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Methods |
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Animals were managed in accordance with the American Heart Association guidelines on research animal use,24 and the protocol was approved by the University of Alabama at Birmingham Institutional Animal Care and Use Committee.
Animal Preparation
Six 36- to 41-kg pigs were injected intramuscularly with Telazol (4.4 mg/kg), xylazine (2.2 mg/kg), and atropine (0.04 mg/kg) for anesthetic induction. Anesthesia was maintained with isoflurane in 100% oxygen by inhalation. Core body temperature, arterial blood pressure, arterial blood gases, ECG lead II, and serum electrolytes were monitored and maintained within normal ranges throughout the study.
The heart was exposed through a median sternotomy and supported in a pericardial sling. A silicone rubber ring with a central opening 15 mm in diameter was sutured onto the anterior wall of the right ventricle.25 Four to 6 suture lines were inserted through the ring and attached to the chest retractor to reduce the local movement of the heart and allow a stable microelectrode recording. An Ag-AgCl reference electrode for the intracellular recording electrode was sutured to the inside of the chest. A catheter (model 6942, Sprint, Medtronic) with a 479-mm2 surface area electrode in the right ventricle and a 766-mm2 surface area electrode in the superior vena cava was inserted for defibrillation.
Signal Recordings
For intracellular recordings, a conventional microelectrode (tip resistance, 10 to 30 M
, filled with 3 mol/L KCl) was mounted on a 30-µm Ag-AgCl spiral wire to allow the microelectrode to follow cardiac motion.26 Action potentials were recorded with DC coupling at the center of the ring as the difference in voltage between the intracellular microelectrode and the extracellular Ag-AgCl reference electrode. The signal was passed through a high-impedance capacitance-compensation preamplifier (model 773, WP Instruments Inc) and was recorded by a mapping system that sampled at 2 kHz and stored the data on 8-mm data cartridge tapes (Exabyte Corporation) for offline analysis.
Experimental Protocol
VF was induced by stimulating the left ventricle with a 9-V battery for 1 second. VF episodes were induced 5 times in each animal. For the first 4 VF episodes, recording lasted for 20 seconds before a rescue shock was delivered. For the fifth episode, VF was recorded for >60 seconds.
Restitution Measurements During Pacing
After the fourth VF episode in the last 3 animals, the APD restitution relationship was determined during pacing. Pacing stimuli were delivered at twice diastolic threshold to the anterior right ventricle. Trains of 30 S1 stimuli were repeated at the intervals described below. Depending on the intrinsic heart rate, pacing started at 450 or 400 ms and was decreased to 300 ms by 50-ms steps. The pacing interval was decreased from 300 to 170 ms by 10-ms steps and then was reduced in 5-ms steps from 170 to an interval that induced VF or lost 1:1 capture. To capture during shorter pacing intervals, the S1–S1 interval was initially 300 ms and then decreased in 10-ms steps to the target interval, and thereafter kept at the target interval for 30 beats (Figure 1).
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Data Analysis
Of the 30 VF episodes that were induced in the 6 animals, 6 were excluded from analysis because of distorted action potential morphology caused by unstable lodging of the microelectrode in the cell. Thus, 24 VF episodes had stable microelectrode recordings and were used for analysis. To eliminate electrotonic signals that did not represent a true action potential, APDs during VF were limited to those with an action potential amplitude >40 mV and 
max>5 V/s, as has been done by others.27,28 Because of the rapid activation rates during VF, complete repolarization rarely occurred. APD60 was measured during a sinus beat immediately before VF induction. The amplitude of the APD60 served as a reference level for determining 60% repolarization of subsequent APDs during VF (Figure 2A). DI was taken as the time interval from the end of APD60 to max of the next APD. APD60 was calculated for the last 2 beats of the 30 paced beats for each S1–S1 interval. DI was taken as the pacing cycle length minus the next-to-last APD60. We also calculated APD60, APD80, and APD90 referred to the amplitude of the upstroke of each individual action potential during VF.
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Statistical Analysis
Data are reported as mean±SD. A value of P<0.05 was considered statistically significant. Linear, sigmoidal, and single-exponential equations were fit to the restitution relationship of APD and DI (Origin, Microcal Software).
Statistical analysis of APD and DI during different periods of VF was performed with Repeated Measures (SPSS, SPSS Inc). Forward stepwise linear regression was used to predict the relationship between APD and previous DIs and APDs (JMP, SAS Institute Inc). APD(n) was the dependent variable, and the previous 3 APDs (n–1, n–2, n–3) and 4 DIs (n–1, n–2, n–3, and n–4) were independent variables (Figure 2B). The procedure was performed on 5-second segments of the VF data. The procedure enters independent variables one at a time in the order in which they most improve the fit to the dependent variable. For a variable to be included, the significance probability attributed to it had to have been 
0.25.
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Results |
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max was 22±13 V/s, and action potential amplitude was 63±20 mV. Although initially, action potentials immediately followed repolarization from the previous action potential with a short DI, after the first 20 seconds of VF, occasional longer DIs began to appear (Figure 3). The mean DI was 20.0±8.1 ms (n=24) for the first 20 seconds of VF and slightly but significantly increased to 24.1±7.5 ms 20 to 40 seconds after VF induction (P<0.01, n=6) and increased further to 28.7+8.7 ms (P<0.01, n=6) 40 to 60 seconds after VF induction. APD60 was 97.3±15.8 during the first 20 seconds of VF (n=24) and decreased significantly (P<0.01, n=6) to 89.7±11.5 ms 20 to 40 seconds and to 89.6±10.7 ms 40 to 60 seconds after VF induction. The latter 2 values are not significantly different. The mean VF cycle length did not change significantly over the 60 seconds of VF. It was 119±17 ms for the first 20 seconds, 121±15 ms for 20 to 40 seconds, and 125±12 ms for 40 to 60 seconds of VF.
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The restitution relation obtained during the pacing protocol was well fit by an exponential function with a mean R2 of 0.92 (range, 0.95 to 0.88, Figure 4). However, when plotted over the entire 60 seconds of VF, the plot of DI versus APD formed a scattered cluster of points rather than a simple sigmoidal or exponential relationship (R2=0.06 and R2=0.05, respectively). When plotted in 10-second segments, a tighter clustering of the data was seen, related to the lengthening of the mean DI as VF continued (Figure 5). Even during these shorter intervals, however, the data did not fit a linear, sigmoidal, or exponential function, and its linear slope was frequently negative (Figure 5). We also tested the relationship between DI and APD80 or APD90, which were measured from the action potential amplitude during each individual VF action potential, and found results similar to those obtained with APD60 on the basis of the action potential amplitude during sinus rhythm. In addition, APD60 based on sinus rhythm was highly correlated with APD60 determined individually for each VF action potential (R=0.94±0.03).
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Stepwise linear regression indicated that 3.0±1.5 of the 7 previous DIs and APDs entered the equation to predict APD(n) during VF. The 2 variables that appeared most frequently in the regression equation were DI(n–1) (70% of 5-second intervals) and APD60(n–1) (71% of intervals, Table). DI(n–1) and APD60(n–1) were the first or second variables entered in 87% and 76% of the intervals in which they were present, respectively. During the first 30 seconds of VF, APD60 was the first or second variable entered significantly more often than was DI(n–1), whereas during the next 30 seconds, DI(n–1) was the first or second variable significantly more often than was APD60(n–1). The coefficients of DI(n–1) and APD60(n–1) were positive in 89% and 98% of the intervals in which they were present, respectively. Thus, the restitution relationship [DI(n–1) versus APD(n)] had a positive slope 89% of the time when the influence of other variables was included, contrasted with the frequent incidence of negative slopes when only the basic restitution relationship was considered (Figure 5). DI(n–2) and APD(n–2) were entered into the stepwise regression function less often (P<0.05) and almost always had negative coefficients. DI(n–3), APD(n–3), and DI(n–4) were entered least often (P<0.05) and had positive coefficients approximately half of the time. The mean±SD of the R2 of the regression for all intervals was 0.39±0.05.
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Discussion |
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To the best of our knowledge, this is the first study to investigate the DI restitution properties during VF in the in situ animal heart. The main findings of this study are that (1) the APD-DI restitution relationship is not well fit by a linear, sigmoidal, or single-exponential curve during the first 60 seconds of VF in the pig; (2) both restitution and memory are significantly related to APD during this period of VF; (3) memory appears to be the more important variable during the first 30 seconds of VF, whereas restitution appears to be more important during the next 30 seconds; and (4) restitution and memory together account for only 39% of the variability of APD.
DI restitution refers to the fact that the cardiac APD depends on the previous DI. In general, a long DI leads to a long APD and vice versa.12,13 In most previous studies, the investigators constructed the restitution relationship after 30 to 50 paced beats at the same cycle length.14,16,17 These curves were well fit by a sigmoidal or exponential function. Most of these investigations focused on the steepness of the restitution curve, because if this slope is >1, then at a constant cycle length, a single perturbation in DI will cause the ensuing APDs and DIs to oscillate, with the oscillations progressively increasing until the site is refractory at the time of the next cycle and block occurs. Drugs that flatten the restitution slope can prevent the occurrence of arrhythmias or convert VF to ventricular tachycardia.16,17 The restitution hypothesis of VF states that the slope of the DI restitution curve is the main determinant of wave break that is responsible for the maintenance of VF.6
Recently, restitution curves were shown with a slope >1 during VF.14,21,22 During those studies, the points of the slope >1 were located in the region in which the APD90 or APD–70 mV was <60 ms. In this study, we also observed short-duration, low-amplitude deflections during VF (Figure 3, 5 to 7 seconds). We excluded those signals from our analysis because these short APDs probably do not represent new action potentials capable of propagation but instead represent a graded response or an electrotonic potential arising from a nearby region of conduction block.21 This assumption is supported by several reports that the refractory period estimated during VF is >60 ms.25,29,30 If these short, small deflections are deleted from the previous studies, then the maximum slopes of the restitution curves are no longer >1 during VF.31
As opposed to those previous studies performed in pieces of heart tissue, we found that a plot of DI versus APD formed a diffuse cluster of points in the intact heart of the open-chested pig (Figure 4). When the plot was divided into 10-second segments of VF, the clusters of points became smaller and shifted to the right as VF progressed, consistent with a change in the restitution relationship with time (Figure 5). Yet, even the smaller clusters were poorly fit by a standard sigmoidal or exponential restitution function, and the slope of the linear regression line was frequently negative. These findings are inconsistent with classic DI restitution with a positive slope as the sole cause for the majority of variation in the APD during VF.
Why is a tight DI restitution relationship present during pacing but not during VF? A likely reason is that during the pacing protocols, the cycle length and the activation sequence are constant, whereas during VF, these variables both change from cycle to cycle. Changes in activation sequence can alter APD through electrotonic influences on repolarization.32 Changes in cycle length expose those effects of cardiac memory that are hidden when the cycle length is constant. The strongest memory effect on APD is the previous cycle length, although the APDs and DIs forming yet earlier cycle lengths also influence APD.19 The primary effect of cardiac memory is to cause an APD after short APDs to be shorter than predicted by the nominal restitution curve and an APD after long APDs to be longer.33 Thus, the memory effect will tend to dampen the oscillations caused by restitution properties.
Stepwise linear regression revealed that both APD(n–1) and DI(n–1) were significantly related to APD(n) (Table). The coefficient of APD(n–1) in the regression equation was almost always positive, consistent with the cardiac memory effect of a previous longer APD causing a longer succeeding APD and vice versa. The coefficient of the previous DI in the regression equation was also almost always positive, consistent with DI restitution in which a longer DI causes a longer ensuing APD and vice versa. The inclusion of the other variables in the stepwise regression unmasked this DI restitution relationship, which was hidden in the standard DI-APD restitution plot.
In addition to the previous cycle, memory effects from even earlier cycles also sometimes entered the stepwise regression. However, the frequency with which the variables entered decreased as they became earlier and thus farther removed in time from the APD in question. In addition, the coefficients of APD(n–2) and DI(n–2) were almost always negative, the opposite of what would be expected for standard memory and DI restitution relationships.
The mean R2 for the stepwise regression was 0.39. Thus, inclusion of DI restitution and memory effects from the 3 previous cycles could not explain 61% of the variation in APD. This finding suggests that other factors, such as electrotonus caused by alterations in activation and repolarization and myocardial structure causing anisotropic effects on conduction and repolarization, also have important effects on APD. Ischemia during VF may also alter the relationship between DI and APD.
Limitations
During the first 20 seconds of VF, we rarely observed a long DI as reported by others,22,28 although longer DIs did occur later during VF (Figure 4, 25 to 47 seconds). This suggests that a shorter excitable gap exists in the in vivo pig heart during early VF than in the perfused pig heart. It was recently confirmed that the number of wave fronts during VF decreases significantly when the heart is isolated23 and that the number of wave fronts is further decreased as tissue mass is decreased.28 Also, as tissue mass is decreased, the cycle length and DI lengthen during VF.28 Therefore, the long DIs observed by others during early VF may have been associated with the isolated, perfused myocardial preparation.
The general anesthesia, open chest, and cooling of the exposed epicardium may all have influenced the results of this study. However, although these influences may have altered the relationship between APD, DI restitution, and cardiac memory, a relationship among these variables, even though altered, should still have been present if they were the primary mechanism for the alteration of APD during VF.
We recorded only from a single right ventricular site. Yet, the ionic currents governing repolarization differ in different regions of the ventricular wall. Therefore, our results may not apply to the whole heart.
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Acknowledgments |
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This study was supported in part by National Institutes of Health research grant HL-28429 and an American Heart Association Science Development Grant. The authors thank Drs Vladimir Fast and Richard Gray for their suggestions to improve the manuscript and Dr Gregory Walcott for his technical support in software.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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- Moe GK, Abildskov JA, Han J. Factors responsible for the initiation and maintenance of ventricular fibrillation. In: Surawicz B, Pellegrino ED, eds. Sudden Cardiac Death. New York, NY: Grune and Stratton; 1964.
- Zhou S, Cao JM, Tebb ZD, Ohara T, Huang HL, Omichi C, Lee MH, KenKnight BH, Chen LS, Fishbein MC, Karagueuzian HS, Chen PS. Modulation of QT interval by cardiac sympathetic nerve sprouting and the mechanisms of ventricular arrhythmia in a canine model of sudden cardiac death. J Cardiovasc Electrophysiol. 2001; 12: 1068–1073.[CrossRef][Medline]
[Order article via Infotrieve]
- Han J. Ventricular vulnerability to fibrillation. In: Dreifus LS, Likoff W, eds. Cardiac Arrhythmias. New York, NY: Grune and Stratton; 1973: 87–95.
- Tovar OH, Jones JL. Epinephrine facilitates cardiac fibrillation by shortening action potential refractoriness. Mol Cell Cardiol. 1997; 29: 1447–1455.[CrossRef][Medline]
[Order article via Infotrieve]
- Karma A. Electrical alternans and spiral wave breakup in cardiac tissue. Chaos. 1994; 4: 461–472.[CrossRef][Medline]
[Order article via Infotrieve]
- Weiss JN, Garfinkel A, Karagueuzian HS, Qu Z, Chen PS. Chaos and the transition to ventricular fibrillation: a new approach to antiarrhythmic drug evaluation. Circulation. 1999; 99: 2819–2826.
[Abstract/Free Full Text]
- Weiss JN, Chen PS, Qu Z, Karagueuzian HS, Lin SF, Garfinkel A. Electrical restitution and cardiac fibrillation. J Cardiovasc Electrophysiol. 2002; 13: 292–295.[CrossRef][Medline]
[Order article via Infotrieve]
- Vinet A, Roberge FA. The dynamics of sustained reentry in a ring model of cardiac tissue. Ann Biomed Eng. 1994; 22: 568–591.[CrossRef][Medline]
[Order article via Infotrieve]
- Pastore JM, Girouard SD, Laurita KR, Akar FG, Rosenbaum DS. Mechanism linking T-wave alternans to the genesis of cardiac fibrillation. Circulation. 1999; 99: 1385–1394.
[Abstract/Free Full Text]
- Cao JM, Qu Z, Kim YH, Wu TJ, Garfinkel A, Weiss JN, Karagueuzian HS, Chen PS. Spatiotemporal heterogeneity in the induction of ventricular fibrillation by rapid pacing: importance of cardiac restitution properties. Circ Res. 1999; 84: 1318–1331.
[Abstract/Free Full Text]
- Karma A. Spiral breakup in model equations of action potential propagation in cardiac tissue. Phys Rev Lett. 1993; 71: 1103–1106.[CrossRef][Medline]
[Order article via Infotrieve]
- Boyett MR, Jewell BR. A study of the factors responsible for rate-dependent shortening of the action potential in mammalian ventricular muscle. J Physiol. 1978; 285: 359–380.
[Abstract/Free Full Text]
- Bass O, McGuigan JAS. Electrical activity and excitation-contraction coupling in mammalian ventricular muscle. Basic Res Cardiol. 1975; 70: 585–595.[CrossRef][Medline]
[Order article via Infotrieve]
- Koller ML, Riccio ML, Gilmour RF. Dynamic restitution of action potential duration during electrical alternans and ventricular fibrillation. Am J Physiol. 1998; 275: H1635–H1642.[Medline]
[Order article via Infotrieve]
- Fox JJ, Riccio ML, Hua F, Bodenschatz E, Gilmour RF, Jr. Spatiotemporal transition to conduction block in canine ventricle. Circ Res. 2002; 90: 289–296.
[Abstract/Free Full Text]
- Garfinkel A, Kim YH, Voroshilovsky O, Qu Z, Kil JR, Lee MH, Karagueuzian HS, Weiss JN, Chen PS. Preventing ventricular fibrillation by flattening cardiac restitution. Proc Natl Acad Sci U S A. 2000; 97: 6061–6066.
[Abstract/Free Full Text]
- Riccio ML, Koller ML, Gilmour RF. Electrical restitution and spatiotemporal organization during ventricular fibrillation. Circ Res. 1999; 84: 955–963.
[Abstract/Free Full Text]
- Wu R, Patwardhan A. Restitution of action potential duration during sequential changes in diastolic intervals shows multimodal behavior. Circ Res. 2004; 94: 634–641.
[Abstract/Free Full Text]
- Rosen MR. What is cardiac memory? J Cardiovasc Electrophysiol. 2000; 11: 1289–1293.[CrossRef][Medline]
[Order article via Infotrieve]
- Choi B-R, Liu T, Salama G. Adaptation of cardiac action potential durations to stimulation history with random diastolic intervals. J Cardiovasc Electrophysiol. 2004; 15: 1188–1197.[CrossRef][Medline]
[Order article via Infotrieve]
- Winfree AT. Various ways to make phase singularities by electric shock. J Cardiovasc Electrophysiol. 2000; 11: 286–289.[Medline]
[Order article via Infotrieve]
- Lee MH, Qu Z, Fishbein GA, Lamp ST, Chang EH, Ohara T, Voroshilovsky O, Kil JR, Hamzei AR, Wang NC, Lin SF, Weiss JN, Garfinkel A, Karagueuzian HS, Chen PS. Patterns of wave break during ventricular fibrillation in isolated swine right ventricle. Am J Physiol. 2001; 281: H253–H265.
- Qin H, Kay MW, Chattipakorn N, Redden DR, Ideker RE, Rogers JM. Effects of heart isolation, voltage-sensitive dye, and electromechanical uncoupling agents on ventricular fibrillation. Am J Physiol. 2003; 284: H1818–H1826.
- AHA Special Report. Position of the American Heart Association on research animal use. Circulation. 1985; 71: 849A–850A.[Medline]
[Order article via Infotrieve]
- 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.
[Abstract/Free Full Text]
- 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.
[Abstract/Free Full Text]
- Yashima M, Kim YH, Armin S, Wu TJ, Miyauchi Y, Mandel WJ, Chen PS, Karagueuzian HS. On the mechanism of the probabilistic nature of ventricular defibrillation threshold. Am J Physiol. 2003; 284: H249–H255.
- Kim YH, Garfinkel A, Ikeda T, Wu TJ, Athill CA, Weiss JN, Karagueuzian HS, Chen PS. Spatiotemporal complexity of ventricular fibrillation revealed by tissue mass reduction in isolated swine right ventricle: further evidence for the quasiperiodic route to chaos hypothesis. J Clin Invest. 1997; 100: 2486–2500.[Medline]
[Order article via Infotrieve]
- Cha Y-M, Birgersdotter-Green U, Wolf PL, Peters BB, Chen P-S. The mechanism of termination of reentrant activity in ventricular fibrillation. Circ Res. 1994; 74: 495–506.
[Abstract/Free Full Text]
- Huang J, Rogers JM, KenKnight BH, Rollins DL, Smith WM, Ideker RE. Evolution of the organization of epicardial activation patterns during ventricular fibrillation. J Cardiovasc Electrophysiol. 1998; 9: 1291–1304.[Medline]
[Order article via Infotrieve]
- Ideker RE, Rogers JM, Gray RA. Steepness of the restitution curve: a slippery slope? J Cardiovasc Electrophysiol. 2002; 13: 1173–1175.[CrossRef][Medline]
[Order article via Infotrieve]
- Burgess MJ, Steinhaus BM, Spitzer KW, Ershler PR. Nonuniform epicardial activation and repolarization properties of in vivo canine pulmonary conus. Circ Res. 1988; 62: 233–246.
[Abstract/Free Full Text]
- Elharrar V, Surawicz B. Cycle length effect on restitution of action potential duration in dog cardiac fibers. Am J Physiol. 1983; 244: H782–H792.[Medline]
[Order article via Infotrieve]
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