Changes in Myocardial Electrical Impedance Induced by Coronary Artery Occlusion in Pigs With and Without Preconditioning
Correlation With Local ST-Segment Potential and Ventricular Arrhythmias
Background Myocardial ischemia increases tissue electrical resistivity leading to cell-to-cell uncoupling, and this effect is delayed by ischemic preconditioning in isolated myocardium. Alterations in myocardial resistivity elicited by ischemia in vivo may influence arrhythmogenesis and local ST-segment changes, but this is not well known.
Methods and Results Myocardial impedance (resistivity [Ω · cm] and phase angle [°]), epicardial ST segment, and ventricular arrhythmias were analyzed during 4 hours of coronary artery occlusion in 11 anesthetized open-chest pigs; these were compared with 13 other pigs submitted to a similar coronary occlusion preceded by ischemic preconditioning. Myocardial resistivity rose slowly during the first 34±7 minutes of occlusion (237±41 to 359±59 Ω · cm), increased rapidly to 488±100 Ω · cm at 60 minutes, and reached a plateau value (718±266 Ω · cm, ANOVA; P<.01) at 150±69 minutes. By contrast, phase-angle changes began after 17 minutes of ischemia (−3.0±1.6° to −4.2±1.2° at 29±8 minutes) and evolved faster thereafter (−12.5±5.3° at 144±56 minutes). Marked changes in myocardial impedance were observed during the reversion of ST-segment elevation that occurred 1 to 4 hours after occlusion, but impedance changes were less apparent during the early ST-segment recovery seen at 15 to 35 minutes of ischemia. The second arrhythmia peak (30±5 minutes) coincided with the fast change in tissue impedance, and both were delayed (P<.05) by ischemic preconditioning.
Conclusions A rapid impairment of myocardial impedance occurs after 30 minutes of coronary occlusion, and its onset is better defined by shift in phase angle than by rise in tissue resistivity. Phase 1b arrhythmias are associated with marked impedance changes, and both are delayed by preconditioning. Reversion of ST-segment elevation is partially associated with impairment of myocardial impedance, but other factors play a role as well.
Acute myocardial ischemia increases intracellular and extracellular electrical resistance and causes cell-to-cell electrical uncoupling.1 Cellular uncoupling occurs as a result of an increase in gap junctional resistance elicited by ischemia-induced accumulation of intracellular Ca2+,2 reduction of ATP content,3 and accumulation of amphipathic lipid metabolites,4 among other things. Changes in intracellular resistance can be estimated in the in situ heart by measurement of the whole-tissue myocardial impedance,5 6 which reflects, in addition to intracellular and extracellular resistance, gap junction conductance and membrane capacitance.7
Increases in intracellular resistance caused by ongoing ischemia may reduce the magnitude of intracellular and extracellular currents that are driven by membrane potential differences created between normal and ischemic cells.8 9 In these circumstances, the extracellular potential gradients that are responsible for the TQ- and ST-segment shifts in local electrograms may decrease and, hence, account for the spontaneous reversion of TQ-segment changes in experimental models8 and for the reduction of ST-segment elevation in patients with acute myocardial infarction.10 11 However, studies correlating myocardial impedance and ST-segment changes in ischemic conditions are lacking.
The rise in intracellular resistance impairs electrical conduction in the ischemic myocardium, and this may favor the genesis of ventricular arrhythmias.12 Recent studies performed in swine13 14 reported a temporal relationship between early phases of acute ischemic arrhythmias (called phase 1a and 1b15 ) and the steep rise in tissue resistivity that is thought to reflect the onset of cellular electrical uncoupling.1 13 Conversely, studies in perfused rabbit heart16 have shown that the onset of the steep rise in myocardial resistivity can be postponed by preconditioning of the myocardium with short-lasting ischemia.16 Therefore, preconditioning could allow us to assess whether an artificially induced adjournment of changes in resistivity is associated with a parallel delay in phase 1b arrhythmias. Such an investigation has not been performed in vivo and could contribute to our insight into the hypothesis that unlike phase 1a, phase 1b arrhythmias are associated with alterations in tissue electrical impedance.
This study was designed to analyze the effects of coronary artery occlusion on myocardial impedance in open-chest pigs with and without ischemic preconditioning and to correlate these changes with local epicardial ST-segment potential and ventricular arrhythmias.
Data were obtained from 26 pigs (25 to 30 kg) anesthetized with α-chloralose (100 mg/kg IV) followed by a continuous perfusion of this drug (25 mg · kg−1 · min−1). Pulmonary ventilation was maintained with a pressure respirator (TransPAC 5K257) at 41% oxygen concentration. The thorax was opened through a midsternotomy, the pericardium was incised, and its free margins were sutured to cradle the heart. The LAD was dissected above the first diagonal branch and was looped with a Prolene 5/0 snare. The two ends of the suture were threaded through a smooth plastic tube. The artery was occluded by sliding the tubing over the suture and clamping it with a small hemostat. Coronary reperfusion was established by release of the ligature. In 13 pigs (group 1), the LAD was occluded for 4 hours, whereas in the remaining 13 pigs (group 2), a similar LAD ligature was preceded by preconditioning of the myocardium with three LAD occlusion-reperfusion sequences lasting 5 minutes for occlusion and 20 minutes for reperfusion. Systemic blood pressure was sampled with a pigtail 7F catheter introduced percutaneously through the right femoral artery. Arterial blood gases were measured at regular intervals and were kept within normal limits. Isotonic saline perfusion was administered to compensate for blood losses. Pigs were handled in accordance with the position of the American Heart Association and the European Community Rules on Research Animal Use. This study was approved by the ethics committee of our institution.
Myocardial electrical impedance (Z) is defined as the voltage (V) measured across the tissue divided by the sinusoidal current (I) applied through it (Z=V/I). Because the cell membranes have capacitative properties,17 the myocardial tissue is not purely resistive, and therefore, there will be a time delay between the voltage and current waves that can be determined from the phase angle of tissue impedance.7 In these circumstances, the impedance (Z) will be a complex number (Z=R+jX), where R is the resistance (in phase component of V with respect to I), j is the imaginary unit (j=), and X is the reactance (in quadrature component of V with respect to I). Therefore, myocardial impedance can be precisely defined by two components: tissue resistance (R) and phase angle [θ=arctan(X/R)]. To exclude the effects of the electrode geometry on tissue resistance measurements, we calculated tissue resistivity (ρ) from the relation r=kρ, where k is the electrode constant obtained by measuring the electrical resistance of a 0.9% saline solution at 25°C of known resistivity (70 Ω · cm) with each electrode probe. We also monitored phase-angle changes because, theoretically, they may allow better definition of the rise in intracellular resistance that impairs cell-to-cell electrical coupling.1 Because phase angle is due to the cell membrane capacitance, the changes in intracellular resistance, which in an equivalent circuit modeling the myocardium is in series with the capacitance,7 will produce a phase-angle shift.
Electrode Probe and Measuring Technique
The probe consisted of four platinum electrodes (5 mm long, 0.4 mm in diameter) mounted as a linear array on an insulating substrate separated by an interelectrode distance of 2.5 mm. This electrode arrangement allows us to consider the current electrodes as point sources.18
Myocardial impedance was measured by an alternating current (10 μA, 1110 Hz) applied through the outer pair of electrodes and by determination of both the in-phase and in-quadrature components of V across the inner pair of electrodes with a high-input impedance lock-in amplifier (Princeton Applied Research model 5110). This technique was chosen because electrode polarization affects tissue measurements to a lesser extent than when a single pair of electrodes is used for both current injection and potential measurement.19 20 Before each impedance measurement, the current flowing through the tissue was determined by measurement of the voltage across a resistance of 56 kΩ placed in series with the tissue. This procedure was undertaken to account for the possible current variations caused by the changes in tissue impedance in the ischemic area. Changes in myocardial impedance were measured at the center of the ischemic area and at remote normal myocardial zones with two probes that were sutured to the epicardium and were connected to the lock-in amplifier via an automatic multiplexor system. The appropriate position of each probe with respect to the ischemic area was verified at the end of the study by injection of 10 mL of 25% fluorescein into the left atrium. The ischemic area appears unstained, whereas the normal myocardium is stained by the dye.
Previous studies on isolated myocardial preparations1 21 have shown a relationship between the sharp increase in tissue resistance and the onset of cellular electrical uncoupling assessed by intracellular potential recordings. Because in the present intact heart model we do not have a direct estimation of cellular uncoupling, the onset of this condition can be only indirectly inferred from the steep impedance changes. Conversely, uncoupling may not start simultaneously in all ischemic cells, because electrical and metabolic derangements are heterogeneously distributed across the ischemic region. The onset of the steep rise in resistivity was determined as the moment at which the first derivative of resistivity versus time was maximal. Phase-angle changes are more sharply demarcated, and in these curves we measured both the maximal rate of change and the earliest time at which a value exceeds 10% of baseline.
Epicardial ST-Segment Potential
Extracellular DC epicardial electrograms were recorded with a multichannel differential amplifier system. Electrodes were made with polyethylene tubes 0.5 mm in diameter containing a cotton thread saturated with isotonic saline solution and were connected to the amplifiers through a Ag/AgCl interface. Thirty-two cotton electrodes were sutured to a rubber membrane at interelectrode distances of 5 mm, forming three parallel rows. This membrane was sutured to the left ventricular epicardium in a direction parallel to the LAD covering an area extending from the acutely ischemic region to the normal myocardial zone. The two impedance probes were inserted parallel to the rows of epicardial cotton electrodes (Fig 1⇓), and impedance measurements were correlated to the mean ST-segment potential values measured in the six cotton electrodes surrounding the impedance probe. Epicardial electrograms were recorded at samples of 2-second duration, digitized at a frequency of 500 Hz, and stored in a computer. In addition, selected analog signals were continuously recorded with a 7-channel Elema ink-jet polygraph. ST segment was expressed as total TQ+ST-segment displacement, because this corresponds to the ST segment recorded by conventional ECG.22
VPBs, VT, and VF occurring during the 4 hours of LAD occlusion were monitored by continuous recording of a conventional ECG with an Elema Mingograf 82 ink-jet polygraph. VT was defined as a succession of more than three VPBs at a rate >100 bpm. Sustained VT was considered to be a VT lasting >30 seconds. Sustained VT and VF were terminated by direct DC electrical countershock of 10 J.
Myocardial impedance, epicardial electrograms, conventional ECGs, and blood pressure were recorded at baseline and during 4 hours of LAD occlusion. ECG and blood pressure were recorded continuously, impedance measurements were taken every 2 minutes, and samples of epicardial electrograms of 2-second duration were acquired every minute during the first 60 minutes of ischemia and every 15 minutes thereafter.
Differences in myocardial resistivity, phase angle, and ST-segment potential during 4 hours of coronary occlusion were assessed by repeated-measures ANOVA with a commercially available software (SYSTAT Inc). Samples were taken at baseline and every hour. Because preconditioning affects primarily the onset of the rapid changes in myocardial resistivity and phase angle, we assessed the differences between groups by applying the ANOVA test to the samples taken at 30, 40, 50, 60, and 70 minutes after coronary occlusion. For this analysis, we normalized the individual curves to their baseline values by subtracting them from each measurement. To assess group differences in early ST-segment changes, the ANOVA test was performed at baseline and at 10, 20, 30, 40, 50, and 60 minutes. Results are expressed as mean±SD, and as a significance test for linear, quadratic, and cubic contrasts, the level was set to P<.05. The assumption of normality for ANOVA residuals was graphically verified with normal probability plots. Correlation between myocardial impedance and ST-segment potential was assessed by linear regression, and results are presented as subject-adjusted regression coefficient.23 Group differences in the onset and in maximal changes of myocardial resistivity and phase angle, in the time to peak of phase 1a and 1b arrhythmias, and in the total number of VPBs were evaluated by Student’s t test.
Coronary artery occlusion induced a significant (P<.01) rise in myocardial resistivity and a decrease in phase angle in the ischemic area but did not elicit appreciable changes in the normal myocardium (Fig 1⇑). Two pigs of group 1 died prematurely because of a nonreversible VF and were excluded from the analysis.
Changes in Tissue Resistivity
As illustrated in Fig 1⇑, 2⇓ to 4 minutes after coronary occlusion, the nonpreconditioned pigs showed an initial slight increase in myocardial resistivity (from 237±41 to 259±41 Ω · cm), which was followed by a progressive rise up to 359±59 Ω · cm at 34±7 minutes. A second phase began thereafter and was characterized by a rapid increase in resistivity leading to values of 488±100 Ω · cm at 60 minutes of coronary occlusion. This second phase was followed by a slow rise until maximal plateau values (718±266 Ω · cm) were reached 150±69 minutes after coronary occlusion. Ischemic preconditioning induced significant (P=.004) differences in the time course of myocardial resistivity during the first 30 to 70 minutes of ischemia (Fig 2⇓). As shown in Fig 3⇓, preconditioning postponed the steep rise in myocardial resistivity (from 34±7 to 52±25 minutes, P=.04), although this treatment did not significantly affect the baseline (209±47 Ω · cm) or the maximal (569±178 Ω · cm) resistivity values.
Changes in Phase Angle
In contrast to the prompt onset of resistivity changes, phase-angle shift was <10% of baseline until 17 minutes of ischemia had elapsed (Figs 1⇑ and 4⇓). After this interval, phase angle slowly decreased from −3.0±1.6° to −4.2±1.2° at 29±8 minutes of occlusion. These initial changes were followed by a sharp shift to −12.5±5.3° at 144±56 minutes, leading to a maximal plateau phase that lasted until the end of the study. The slope of the phase-angle shift after 30 minutes of coronary occlusion was greater than the slope of the concurrent rise in resistivity (% change from baseline per minute, 4.9±3.1% versus 2.3±1.3%, P=.01). Ischemic preconditioning induced significant (P=.004) differences in the time course of tissue phase-angle shift during the first 30 to 70 minutes of ischemia (Fig 2⇑). This treatment postponed (Fig 3⇑) the onset of the sharp phase-angle deviation (29±8 versus 53±27 minutes, P=.01) but did not exert a significant influence on baseline (−2.3±2.3°) or on maximal (−11.3±4.3°) phase-angle values. Preconditioned pigs showed slight phase-angle changes during the first 17 minutes of ischemia, but these were not significantly different from those in the nonpreconditioned series.
Epicardial electrodes located in the ischemic area showed significant (P<.01) ST-segment elevation during the 4 hours of coronary occlusion in both series of pigs. In the nonpreconditioned group (Fig 1⇑), ST-segment potential depicted an early sharp rise up to 22.1±4.8 mV at 15 minutes. This was followed by a transient reversion of ST segment to 11.4±6.3 mV at 35 minutes and by a subsequent reelevation up to 18.0±4.8 mV at 60 minutes of ischemia. From 1 hour onward, ST-segment elevation declined progressively to 9.2±2.8 mV. Preconditioned pigs attained a similar ST-segment peak at 15 minutes of ischemia (23.5±6.8 mV) and a comparable ST-segment decline (8.8±2.1 mV) at 4 hours of occlusion (Fig 2⇑). By contrast, during the first 30 to 35 minutes of ischemia, the preconditioned series showed a less marked ST-segment recovery (21.5±13.1 mV, P=.01) than nonpreconditioned pigs, although the ST-segment dispersion was larger because four preconditioned pigs still showed transient ST-segment recovery (Fig 2⇑).
VPBs depicted a three-phase pattern (Fig 5⇓). The first phase began 2 minutes after occlusion, peaked at 6±2 minutes, and ended ≈20 minutes later. After a brief arrhythmia-free period, there was a second arrhythmia phase peaking at 30±5 minutes, which vanished 1 hour after occlusion. The third arrhythmia period began ≈75±3 minutes after occlusion and lasted until the third hour of coronary occlusion. Ischemic preconditioning (Fig 5⇓, bottom) attenuated the incidence of VPBs (total events, 2110 versus 2905, P<.05), especially during the third phase. In addition, preconditioning delayed the time to the peak of the second phase of ventricular ectopic activity (53±25 versus 30±5 minutes, P=.02) but had no significant effect on the time to peak of the first arrhythmia phase.
The incidence and temporal distribution of more severe forms of ventricular arrhythmias are illustrated in Fig 6⇓. Two of the 13 nonpreconditioned pigs (Fig 6A⇓) died prematurely because of nonreversible VF. Episodes of nonsustained VT occurred in 8 of these remaining 11 pigs and tended to group into two phases, like those of ventricular ectopic activity. Sustained VT developed in 5 pigs, whereas VF occurred in 9 of the 13 nonpreconditioned pigs. Preconditioning (Fig 6B⇓) did not significantly modify the incidence of malignant ventricular arrhythmias.
The relationship between ST-segment and myocardial impedance is complex (Fig 1⇑). ST-segment elevation peaking at 15 minutes of ischemia was not accompanied by phase-angle shift, and only a slight rise in resistivity was observed. Between 15 and 60 minutes of ischemia, resistivity and phase angle shifted monotonically while ST-segment elevation depicted a reversion followed by a transitory reelevation. From 1 hour of coronary occlusion onward, ST-segment elevation decreased progressively, and tissue resistivity and phase angle attained maximal plateau values in both nonpreconditioned (Fig 1⇑) and preconditioned series (Fig 2⇑). However, during this late period of time, the correlation between ST-segment potential and tissue resistivity (r=−.26 for nonpreconditioned and r=−.17 for preconditioned series) and between ST segment and phase angle (r=.31 and r=.16 for each group, respectively) did not reach statistical significance.
Ventricular ectopic activity peaking at 6 to 10 minutes of coronary occlusion was associated with a slight rise in tissue resistivity but was not accompanied by phase-angle changes. By contrast, the second arrhythmia period, occurring at ≈30 minutes of ischemia, was accompanied by a sharp change in resistivity and phase angle, and all these variables were delayed by ischemic preconditioning. The third arrhythmia phase was associated with maximal resistivity and phase-angle values.
Tissue Impedance of Ischemic Myocardium
This study shows that coronary artery occlusion causes alterations in myocardial electrical impedance that are characterized by a rise in tissue resistivity beginning immediately after occlusion and by a negative phase-angle shift that starts after 17 minutes of ischemia.
The mechanism underlying the changes in myocardial impedance in the in situ ischemic heart is not well known. The sharp rise in tissue resistivity has been related to cell-to-cell electrical uncoupling in ischemic heart preparations,1 2 24 but data on phase-angle changes elicited by coronary occlusion are scant.25 The major determinants of myocardial impedance are the extracellular and intracellular resistance, the gap junction conductance, and the cell membrane capacitance.5 6 7 Extracellular resistance increases during the first 10 to 15 minutes of ischemia in the perfused papillary muscle1 as a result of the collapse of the extracellular compartment caused by cessation of coronary perfusion and by osmotic cell swelling.26 By contrast, intracellular resistance increases after 10 to 15 minutes of ischemia1 and leads to cellular electrical uncoupling as a result of a drop in gap junctional conductance induced by, among other things, the intracellular accumulation of both free Ca2+2 and amphipathic lipid metabolites4 and the reduction of ATP content3 in the ischemic myocardium. Intracellular acidosis affects gap junction conductance,27 but it does not appear to be a major trigger for cellular uncoupling during ischemia.2
Assuming that the time course of extracellular and intracellular resistance changes in the ischemic papillary muscle1 could be extrapolated to the in situ heart, there would be a temporal relationship between the initial increase in extracellular resistance and the immediate slow rise in tissue resistivity. Likewise, the subsequent increase in intracellular resistance would correlate with the sharp phase-angle and resistivity changes. To further interpret the alterations in myocardial impedance, an equivalent circuit composed by two parallel branches modeling the passive electrical elements of the myocardium7 may be considered: one branch modeling the extracellular resistance and a second branch composed of a series of three elements modeling the membrane capacitance, the intracellular resistance, and gap junctional resistance, respectively. Because phase-angle shift is caused by membrane capacitance,17 the initial changes in extracellular resistance, which in the equivalent circuit is in parallel with this capacitance, will affect tissue resistivity more than phase angle, as seen during the first 17 minutes of coronary occlusion in our study. By contrast, the ensuing rise in intracellular resistance,1 which in the equivalent circuit is in series with the capacitance, may account for both the phase-angle shift that begins after 17 minutes of ischemia and the further rise in resistivity seen in this study as well. Thus, the alterations in intracellular resistance that lead to cell-to-cell electrical uncoupling may be better defined by the changes in phase angle than by the changes in tissue resistivity. However, because no direct assessment of the uncoupling process is made in this study, we cannot precisely ascertain which moment of the phase-angle changes indicates the onset of uncoupling. Moreover, uncoupling is not expected to begin simultaneously in all ischemic cells, provided that electrical and metabolic derangements are not uniformly distributed in the ischemic area.
This study reveals that ischemic preconditioning postpones the steep changes in both tissue resistivity and phase angle, and this is in agreement with the delayed rise in resistivity seen in preconditioned papillary muscle.16 The mechanism by which preconditioning postpones the impairment of passive myocardial properties has been linked to activation of the IK-ATP channel, because this delay can be abolished by the channel blocker glibenclamide or, to the contrary, reproduced by the IK-ATP opener cromakalim.16 Conversely, preconditioning postpones the onset of intracellular Ca2+ accumulation,2 a circumstance that impairs gap junctional conductance.27 Compared with nonpreconditioned series, preconditioned pigs show slight phase-angle changes during the first 17 minutes of ischemia, suggesting that the three episodes of ischemia and reperfusion performed before the sustained coronary occlusion might have yielded residual abnormalities in intracellular resistance, but this needs to be confirmed.
Myocardial Impedance and ST-Segment Changes
Myocardial ischemia impairs active electrical cell properties,8 9 and this creates membrane potential differences between the ischemic and normal zones that are responsible for TQ- and ST-segment shifts in extracellular recordings.8 9 The current flowing as a result of the regional membrane voltage differences is expected to decrease when tissue resistivity increases in the ischemic region,28 29 thus leading to TQ- and ST-segment potential attenuation. This circumstance might explain the spontaneous decline in the magnitude of the ST-segment elevation seen in patients with acute myocardial infarction,10 11 but correlative studies between ST-segment and myocardial impedance in ischemic intact heart are lacking. Our study reveals that there is a transient ST-segment recovery at 15 to 30 minutes of ischemia associated with minor impedance changes, whereas 1 hour after occlusion, ST-segment elevation declined progressively and impedance changes attained their maximal values. The early ST-segment potential decline has been described previously in the porcine model30 and bears a temporal relationship with the well-recognized transitory improvement of action potential characteristics of ischemic cells,8 9 which coincide with the plateau phase of extracellular K+ accumulation. It might therefore be anticipated that the recovery of active cell properties will reduce the regional membrane potential differences responsible for ST-segment shift and hence play a major role in early ST-segment recovery. We observed that ischemic preconditioning tends to lessen the magnitude of transient ST-segment recovery, but the mechanism of this action is uncertain. In accordance with the early ST-segment recovery, other studies in pigs13 have reported reversion of TQ-segment displacement 20 to 30 minutes after coronary occlusion, although correlative ST-segment data were not available. Reversion of ST-segment elevation after 1 hour of occlusion is associated with marked myocardial impedance changes, suggesting a relationship between these two phenomena. Other factors, however, such as the loss of membrane potential caused by irreversible cell membrane damage, may further reduce the regional membrane potential differences between normal and ischemic myocardium and therefore attenuate the ST-segment shift.
Myocardial Impedance and Ventricular Arrhythmias
Recent studies by Smith et al13 and by our group14 in anesthetized pigs show that phase 1a arrhythmias coincide with the initial slow rise in myocardial resistivity and that phase 1b arrhythmias concur with the steep rise in resistivity. Present data further evidence that these arrhythmias can be better defined by the changes in tissue phase angle, because phase 1a arrhythmias are not associated with significant changes in tissue phase angle, whereas phase 1b arrhythmias coincide with the fast phase-angle shift. The third arrhythmia phase began 1 hour after coronary ligature and coincided with maximal values of tissue resistivity and phase angle. In addition to the relationship with tissue impedance changes, phase 1a arrhythmias coincide with the first rise in extracellular K+ accumulation and with progressive acidosis in the ischemic area, whereas phase 1b arrhythmias concur with the second rise in K+.13 Changes in extracellular K+ concentration are heterogeneously distributed in the ischemic myocardium,31 and they can be used as a surrogate for the ionic and metabolic derangements induced by ischemia, because K+ changes correlate with the alterations in intracellular Ca2+, intracellular and extracellular pH, tissue resistance, and phosphocreatine and ATP elicited in the ischemic myocardium.24
Alterations in tissue impedance may depress conduction of the excitation wave front12 and favor the maintenance or the initiation of reentrant arrhythmias. The mechanism underlying the distinct phases of early ischemic arrhythmias is not entirely known. Multisite recordings of local electrograms28 32 suggest a reentrant mechanism for phase 1a arrhythmias. By contrast, attenuation of phase 1b arrhythmias after β-blockade33 or after myocardial denervation34 may indicate that these arrhythmias might be caused by abnormal automaticity, provided that this arrhythmogenic mechanism is linked to the action of catecholamines. Present data suggest that alterations in intracellular resistance may play a role in the genesis of phase 1b and late (2 to 4 hours) ischemic arrhythmias but not those of phase 1a. This assumption is further strengthened by the fact that preconditioning postpones, in a parallel fashion, both the steep changes in myocardial impedance and the peak of the phase 1b arrhythmias.
The beneficial effect of preconditioning on reperfusion arrhythmias has been largely recognized,35 36 37 but its influence on arrhythmias during acute coronary occlusion is less well known. In our series, preconditioning attenuated the incidence of VPBs during coronary occlusion but not the incidence of more severe ventricular arrhythmias. Other studies report reductions in the number of severe ventricular arrhythmias during coronary occlusion in preconditioned hearts.35 38 39
Selected Abbreviations and Acronyms
|LAD||=||left anterior descending coronary artery|
|VPB||=||ventricular premature beat|
This study was supported by grants from Hospital Universitary Vall d’Hebron (PRHG 95/91), Barcelona, and from Fondo de Investigaciones Sanitarias (FIS 95/1247), Madrid, Spain.
- Received March 6, 1997.
- Revision received May 19, 1997.
- Accepted May 28, 1997.
- Copyright © 1997 by American Heart Association
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