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First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata 990-9585, Japan
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ABSTRACT |
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Although a relationship between S-T alternans and life-threatening arrhythmia has been recognized, the mechanism is poorly understood. We examine the role of S-T alternans in the occurrence of ventricular fibrillation (VF) after reperfusion. The left anterior descending coronary artery was occluded for 20 min and then abruptly reperfused in 12 intravenously anesthetized open-chest dogs. Sixty unipolar epicardial electrograms were recorded during the control state, at the end of occlusion, and after reperfusion. The largest magnitude of S-T alternans among 60 leads was defined as the maximum S-T alternans. Isochronal maps of activation time in paced beat and spontaneous ventricular premature contractions (VPC) were analyzed. After reperfusion, VF ensued in six dogs. The maximum S-T alternans augmented progressively with time after reperfusion until VF occurred. In three dogs with VF, when activation of VPC resulted in conduction block and formed reentry, VF ensued. The conduction block was located between sites of discordant S-T alternans (S-T alternans at adjacent leads was out of phase). These data indicate that discordant S-T alternans relates to VF by facilitating the formation of a reentrant circuit.
ventricular fibrillation; conduction block; reentrant circuit
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INTRODUCTION |
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Abstract
Introduction
Methods
Results
Discussion
References
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THE PHENOMENON of S-T alternans has frequently been noted in the presence of myocardial ischemia (2, 4, 12, 20). The magnitude of S-T alternans temporally associates with the occurrence of ventricular fibrillation (VF) (4, 20), especially during the reperfusion phase (2, 5, 18). Several reports speculated that generation of excitatory current (1, 12, 13) or reentrant circuit by S-T alternans caused VF (5, 20). Recently, Rosenbaum et al. (19) reported that electrical alternans affecting the S-T segment and T wave was common in patients with increased risk for ventricular arrhythmias. However, the mechanism by which S-T alternans causes VF remains poorly understood.
Previously, we have demonstrated that the risk of VF increases when the magnitude of S-T alternans increases, especially when the S-T alternans is discordant (i.e., the S-T changes in the adjacent leads are out of phase) during acute myocardial ischemia in dogs (14). Because S-T alternans reflects the alteration of action potential duration (3, 13, 20), a discordant appearance of the S-T alternans may indicate spatial inhomogeneity in action potentials. Therefore, we hypothesized that, around the area of discordant S-T alternans, conduction was blocked and a reentrant circuit was formed, facilitating the occurrence of VF. The goal of the present study was to elucidate, by use of the mapping of epicardial electrograms in dog hearts, a correlation between spatial distribution of S-T alternans and subsequent VF after coronary reperfusion.
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METHODS |
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Abstract
Introduction
Methods
Results
Discussion
References
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Surgical preparation. This study conformed to the guiding principles of animal experiments in our institution. Thirteen mongrel dogs (13-21 kg) were anesthetized with an intravenous administration of 30 mg/kg pentobarbital sodium. Under positive-pressure ventilation with room air supplemented with oxygen (3-5 l/min), the thorax was opened in the fifth intercostal space, the pericardium was opened, and a pericardial cradle was made to support the heart at an appropriate position. Arterial pressure, blood gases, and pH were monitored. The PO2, PCO2, and pH of the arterial blood were maintained within the physiological range. The sinus node was crushed, and the right atrium was paced at a cycle length of 400 ms.
Mapping of epicardial electrograms. The heart was wrapped in an array of 60 unipolar electrodes (14, 15). These electrodes were made of fine silver wires (0.005-in. diameter) that were insulated except at the point of attachment. The electrode array had 6 rows and 10 columns (15). The interelectrode distance was 7-10 mm. All recording electrodes were referenced to a Wilson's central terminal. Data were digitized at a sampling frequency of 1,000 Hz using a multichannel data-recording system (CD-G015, Chunichi Denshi, Nagoya, Japan) (11). We can record electrograms for 4 s at voluntary timing with this system. The data were stored on a magneto-optical disk.
Experimental protocol. The left anterior descending coronary artery was ligated for 20 min and was reperfused abruptly. Each recording was repeated during the control state, at the end of occlusion, and immediately after reperfusion. We recorded the beginning of VF after reperfusion with repeated recordings (success rate: 5/6). One dog was excluded from the following analysis because VF occurred during 20 min of coronary occlusion.
Measurements. The flat portion of the P-R segment was defined as zero level. The amplitude of the S-T segment was measured at 40 ms from the J point, and the S-T elevation was defined when the level exceeded 1 mV. The magnitude of S-T alternans was derived as the difference in the level of the S-T segment between two consecutive electrograms. When we illustrated the distribution of S-T alternans, we accepted the leads in which S-T alternans was more than 0.5 mV. When the S-T alternans at adjacent leads was in phase, this condition was named "concordant"; and when it was out of phase, it was named "discordant."
The activation of each electrogram was defined at the minimum derivative of the QRS signal (21). Isochronal maps of epicardial activation were constructed with isochrones delineated by closed contours at 10- or 20-ms intervals. Because there is no accurate way to distinguish very slow conduction from conduction block, we arbitrarily decided that possible conduction block occurred when the difference in activation time between two adjacent leads was >50 ms during a single cardiac cycle (6).Statistical analysis. Mann-Whitney's U test was used to compare values between groups with and without VF. Wilcoxon matched-pairs ranks test was used to compare values before and after reperfusion. Quantitative data were expressed by means ± SD. Differences were considered significant at P < 0.05.
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RESULTS |
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Abstract
Introduction
Methods
Results
Discussion
References
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VF was observed in 6 of 12 dogs (VF group), and the average onset of VF was at 42 ± 26 s after reperfusion. The other six dogs did not show VF 2 h after reperfusion (non-VF group). In all of the non-VF group, we verified that S-T elevation recovered to baseline.
S-T elevation and S-T alternans in VF and non-VF groups. The number of leads showing S-T elevation, the maximal level of S-T elevation, and the maximal magnitude of S-T alternans (maximum S-T alternans) before and after reperfusion are summarized in Table 1. There were no significant differences in number of leads showing S-T elevation or in maximal S-T elevation between the VF and non-VF groups either before or after reperfusion. There was also no significant difference in maximum S-T alternans before reperfusion between VF and non-VF groups. The maximum S-T alternans of the VF group was significantly greater than that of the non-VF group after reperfusion (6.9 ± 4.8 vs. 1.6 ± 0.2 mV, P < 0.01). Figure 1 shows the time course of maximum S-T alternans during 60 s after reperfusion in each dog. In the VF group, the maximum S-T alternans increased progressively with time until the appearance of VF. On the other hand, the maximum S-T alternans of the non-VF group remained relatively constant at a low level after reperfusion.
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S-T alternans and activation sequence of VPC after reperfusion. We could evaluate the activation sequence of ventricular premature contractions (VPC) after reperfusion in five dogs for each group by use of isochronal maps. Figure 2 shows the S-T alternans and activation sequence at both atrial pacing and VPC in representative cases of the VF group (dog C, Fig. 2A) and the non-VF group (dog H, Fig. 2B) after reperfusion. In the isochronal map of Fig. 2A, top right, the relationship between open and closed circles indicated discordant S-T alternans. In Fig. 2A, the isochronal map during atrial pacing showed no conduction block. However, the VPC that occurred at 18 s after reperfusion (VPC1) resulted in a functional conduction block between leads E1 and F1 (represented by heavy solid line). The activation wavefront circulated around both ends of the block, coalesced, and reached the distal side of the block at 70-ms isochrone. The lead of the earliest activation of VPC2 was located on F1 (activation time was 181 ms, where time 0 was the earliest activation of VPC1), and the activation sequence was similar to that in VPC1. These isochronal maps suggested that a reentrant circuit was formed. This activation led to ventricular tachycardia (VT), and VF occurred after VF continued for several seconds. The activation sequences in VT beats were also similar to those in VPC2. As illustrated by the isochronal map in Fig. 2A, top right, the conduction block was seen between sites with discordant S-T alternans. The earliest activation of VPC1 was consistent with the border of the S-T elevation area but not with the location of S-T alternans.
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DISCUSSION |
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Abstract
Introduction
Methods
Results
Discussion
References
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In the VF group, the magnitude of maximum S-T alternans progressed with time until VF occurred. The activation sequence of the VPC in three dogs of the VF group indicated that the conduction was blocked between sites with discordant S-T alternans. The activation sequence after the VPC suggested that a reentrant circuit was formed.
S-T elevation and alternans in reperfusion arrhythmia. There were no differences in the extent (i.e., number of leads with S-T segment elevation) or magnitude of S-T segment elevation between VF and non-VF groups either before or after reperfusion. The lack of correspondence between S-T segment changes and the propensity for VF was previously reported during ischemia (14) and after reperfusion (18). These data suggested that the level of S-T elevation during coronary occlusion or after reperfusion was not always a good predictor of VF. In accord with several reports (2, 5, 14, 18), we observed that the increase of magnitude and discordant appearance in S-T alternans, not S-T level, was a sensitive sign for reperfusion-induced VF.
Mechanism of S-T alternans. Although the mechanisms of S-T alternans are still unclear, the following possible mechanisms have been discussed: 1) calcium load, 2) chemical products, and 3) 5-HT receptor. Increase in calcium levels in ischemic myocardium is a well-known phenomenon (23). Because the S-T alternans during coronary occlusion was attenuated by the administration of calcium antagonists (8, 16), calcium overload may be responsible for the appearance of S-T alternans. Washout chemical products from the ischemic myocardium also are postulated to induce S-T alternans after reperfusion (22). Hirata et al. (9) reported that acidic perfusion increased electrical alternans. The products that affected intra- and extracellular pH may also contribute to augment S-T alternans after reperfusion. Recently, it was reported that nexopamil, a calcium channel and 5-HT2 receptor blocker, attenuated T-wave alternans during and after coronary occlusion rather than diltiazem (17). This result suggested that 5-HT2 receptors may also contribute to electrical alternans.
Activation sequence of VPC. The analysis of the activation sequence of VPC in the VF group demonstrated that the local conduction block along the boundary of discordant S-T alternans induced VF. As shown in the isochronal maps in Fig. 2A and Fig. 3, the depolarization wavefront of VPC spread via the circulation around the conduction block and reached the distal side and then reactivated the proximal side of the block. These activation sequences suggested that reentry was formed. S-T alternans has been shown to be associated with alternans of action potential duration (APD) (3, 13, 20, 24) or effective refractory period (ERP) (7) in experimental studies. The border of discordant S-T alternans was supposed to reflect the zone where APD or ERP was drastically changed. These lines of data suggest that a conduction block and reentrant circuit were created by heterogeneity of ventricular repolarization, as shown regionally by discordant S-T alternans.
We used whole heart mapping for the analysis. This technique allowed us to analyze the macroreentry circuit and S-T alternans distribution at the same time. To our knowledge, this is the first report that the border of discordant S-T alternans contributes to the conduction block and reentrant circuit.Electrophysiological mechanisms of reperfusion arrhythmia and S-T alternans. We found in the present study that the discordant appearance of S-T alternans contributed to the formation of the reentrant circuit during reperfusion. In three dogs of the VF group, the analysis of activation sequences revealed that the reentry was the most probable mechanism for maintaining VT. In the remaining two dogs, the activation sequence of VPC did not show the conduction block and the activation was initiated from the border of ischemic and nonischemic myocardium. Ideker et al. (10) reported that ventricular activation during the transition to VF arose near the border of the ischemic-reperfused region. Janse et al. (12) also reported that injury current at the border area causes a spontaneous activity in ischemic and ischemia-reperfusion myocardium. Our observation in the two dogs may agree with these reports.
Clinical implications. Electrical alternans was regionally specific and was linearly projected to the precordium (18). Therefore, the monitoring of S-T alternans distribution on precordal leads may be useful for evaluating the vulnerability to VF after coronary reperfusion. Such evaluation of the vulnerability to VF would be helpful in patients with thrombolytic therapy, Prinzmetal's angina, and spontaneous recanalization of acute myocardial infarction.
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ACKNOWLEDGEMENTS |
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This study was supported in part by Grants 07670749 and 08670756 from the Ministry of Education, Science, Sports, and Culture of Japan and by a grant from the Japan Research Foundation for Clinical Pharmacology.
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FOOTNOTES |
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Address for reprint requests: H. Tachibana, First Dept. of Internal Medicine, Yamagata Univ. School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
Received 22 July 1997; accepted in final form 20 March 1998.
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REFERENCES |
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Discussion
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29 ms;
dog D) and 39 ms (77