Effects of acute reduction of temperature on ventricular fibrillation activation patterns

¹ Service of Cardiology, Valencia University Clinic Hospital; Departments of ² Electronics and ⁴ Physiology, Valencia University; and ³ Department of Electronic Engineering, Valencia Polytechnic University, 46010 Valencia, Spain

	ABSTRACT

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Because of its electrophysiological effects, hypothermia can influence the mechanisms that intervene in the sustaining of ventricular fibrillation. We hypothesized that a rapid and profound reduction of myocardial temperature impedes the maintenance of ventricular fibrillation, leading to termination of the arrhythmia. High-resolution epicardial mapping (series 1; n = 11) and transmural recordings of ventricular activation (series 2; n = 10) were used to analyze ventricular fibrillation modification during rapid myocardial cooling in Langendorff-perfused rabbit hearts. Myocardial cooling was produced by the injection of cold Tyrode into the left ventricle after induction of ventricular fibrillation. Temperature and ventricular fibrillation dominant frequency decay fit an exponential model to arrhythmia termination in all experiments, and both parameters were significantly correlated (r = 0.70, P < 0.0001). Termination of the arrhythmia occurred preferentially in the left ventricle and was associated with a reduction in conduction velocity (60% in left ventricle and 54% in right ventricle; P < 0.0001) and with activation maps predominantly exhibiting a single wave front, with evidence of wave front extinction. We conclude that a rapid reduction of temperature to <20°C terminates ventricular fibrillation after producing an important depression in myocardial conduction.

ventricular arrhythmias; defibrillation; mapping; spectral analysis

	INTRODUCTION

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TEMPERATURE INFLUENCES the electrophysiological properties of cardiac cells (10, 12, 28). Hypothermia increases the duration of the ventricular action potentials and prolongs the ventricular effective refractory period (1, 2, 10, 12, 15, 28, 29, 31). Myocardial cooling depolarizes the resting membrane potential (10, 28) and decreases the maximum rate of phase 0 of the action potential, the conduction velocity, the peak potentials reached during depolarization (19, 27, 28, 31), and the delayed rectifier and inwardly rectifying potassium currents (10, 15, 27). Hypothermia is associated with an increased susceptibility for ventricular arrhythmias and ventricular fibrillation (VF) (2, 19, 20, 30, 31), and this effect has been related to slowing of conduction, a heterogeneous increase in ventricular repolarization, and the dispersion of refractoriness (25, 29). On the other hand, myocardial cooling has also been used to modify different cardiac rhythm disturbances. Thus descriptions have been made of the protective effect of mild hypothermia on ventricular arrhythmias in experimental models (9), and myocardial cooling has been used to terminate reentrant arrhythmias induced in isolated atrial preparations (26), to shorten mean atrial fibrillatory cycle length in Langendorff-perfused rabbit hearts (8), and for the management of supraventricular arrhythmias after heart surgery (11, 22).

Although information is available on the arrhythmogenic effects of hypothermia, no systematic studies have been made of the way in which hypothermia acts on VF once the latter has been induced. The activation patterns during VF depend on the electrophysiological properties of myocardial cells (4, 5, 14, 16, 18, 23, 33, 36), and these properties are temperature dependent (1, 2, 10, 15, 19, 27-29, 31). Thus hypothermia can influence the mechanisms that intervene in the sustaining of VF, and we hypothesized that a rapid and profound reduction of myocardial temperature impedes the maintenance of VF, leading to termination of the arrhythmia. The aim of the present study was to analyze the modification of VF activation patterns induced by the acute reduction of myocardial temperature in Langendorff-perfused rabbit hearts with high-resolution epicardial mapping, transmural recordings of ventricular activation, and both time- and frequency-domain techniques.

	METHODS

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Experimental Preparation

This study complies with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health [DHHS Publication no. (NIH) 85-23, revised 1996]. Twenty-one California rabbits (mean wt 3.8 ± 0.4 kg) were used. After anesthesia with ketamine (25 mg/kg im) and heparinization, the hearts were removed and immersed in cold (4°C) Tyrode solution. After isolation, the aorta was connected to a Langendorff system for perfusion of Tyrode solution at a pressure of 60 mmHg and a temperature of 37 ± 0.5°C. The composition of the perfusion fluid was (mM) 130 NaCl, 24.2 NaHCO₃, 4.7 KCl, 2.2 CaCl₂, 1.2 NaH₂PO₄, 0.6 MgCl₂, and 12 glucose. Oxygenation was carried out with a mixture of 95% O₂ and 5% CO₂. In series 1 (n = 11) two plaques, one with 121 and the other with 114 unipolar stainless steel electrodes (electrode diameter = 0.125 mm, interelectrode distance = 1 mm), were positioned at the epicardial surface of the lateral wall of both ventricles. In series 2 (n = 10) three plaques, each with four transmural plunge needle electrodes (diameter = 0.20 mm) in a quadrangular arrangement (5 mm each side), were sutured to the lateral wall of the left ventricle (LV). Each plunge electrode contained three unipolar stainless steel electrodes (interelectrode distance = 2.5 mm) located at the tip (subendocardium), midzone (midmyocardium), and base (epicardium). Correct electrode positioning was verified at the end of each experiment by perpendicularly sectioning the endocardium to examine the location. Right ventricle (RV) epicardial activation was recorded as in series 1. The reference electrode was a 4 × 6-mm silver plaque located over the cannulated aorta. Recordings were obtained with a cardiac electrical activity mapping system (MAPTECH). The electrograms were amplified with a gain of 50-300, broadband (1-400 Hz) filtered, and multiplexed. The sampling rate in each channel was 1 kHz. Epicardial temperature (T_p) was recorded by two thermocouples placed in the surface of both ventricles. An additional thermocouple was placed within the LV to record endocardial T_p. This thermocouple was used to obtain baseline measurements and was removed from the ventricle before myocardial cooling was started, to avoid reflux of the cold perfusate through the mitral valve.

Experimental Protocol and Data Analysis

VF was induced by pacing at increasing frequencies, maintaining coronary perfusion during the arrhythmia. Five minutes after the onset of VF, cold oxygenated Tyrode (4°C) was injected into the LV (30 ml at 1 ml/s) with a cannula inserted through the orifice of a pulmonary vein. This procedure initiated myocardial cooling in the LV and immediately afterwards (via coronary perfusion) in the whole heart. During the injection of cold Tyrode, an increase in aorta perfusion pressure was observed that did not exceed 12 mmHg. With the aim of determining whether the site of injection of the cold Tyrode influenced the results obtained, two additional series of experiments [series 1' (n = 8) and series 2' (n = 8)] were conducted with the same experimental protocols as series 1 and 2, respectively, with the exception that the cold, oxygenated Tyrode was injected directly into the aorta instead of into the LV. During the experiments the heart was not superfused with warm solution. The parameters recorded are described below.

Spectral analysis of VF. Welch's method (21) was used to obtain the power spectrum of the signals recorded with six electrodes in series 1, three corresponding to each ventricle. In series 2 the analyzed recordings were obtained with nine electrodes (3 at the subendocardium, 3 at the midmyocardium, and 3 at the epicardium). The analysis was performed with data blocks of 1,024 points (sampling rate = 1 kHz) and was carried out over 60 s from 2 s before the start of myocardial cooling. The dominant frequency (FrD) was obtained for each block. Data processing was performed with Matlab software on a Hewlett-Packard 712/80 platform.

Time-domain analysis of VF. Activation times in each electrode were determined by identifying the moment of maximum negative slope of the electrograms. The minimum threshold for time derivative of an electrogram (dV/dt) to be judged as a local deflection was a percentage (20%) of the maximum negative slope in each channel. If electrograms exhibited two or more deflections, the steepest slope of the activation complex was assigned as the local activation time. The fibrillation interval (VV interval) histograms and the mean of the consecutive VV intervals were determined during three 2-s time windows located immediately before the start of cold Tyrode injection, 20 s after the start of injection, and in the 2 s before the termination of VF.

Analysis of epicardial activation maps during VF. In series 1 the activation maps were constructed in both ventricles in the same 2-s time windows selected for the time-domain analysis of VF. Each map was classified into three categories based on its complexity: type I, single broad wave fronts propagating uniformly; type II, two wave fronts or one wave front with areas of conduction block or slow conduction; and type III, three or more wave fronts associated with areas of slow conduction and conduction block. The presence of activation patterns corresponding to complete reentry and epicardial breakthrough was analyzed by displaying successive 10-ms time windows (5-7). The conduction velocity during VF was determined from the maps with a single wave front without evidence of breakthrough and was calculated by dividing the distance between two electrodes positioned five interelectrode spaces apart in a direction perpendicular to the isochrones by the difference between their activation times (average of 5 determinations) (5).

Statistical Analysis

Data are presented as means ± SD. Comparisons between two sets of data were made with Student's t-test for paired and unpaired data, with Bonferroni's correction for multiple comparisons. The differences between qualitative variables were analyzed by the ²-test. Differences were considered significant at P < 0.05. The linear regressions between pairs of variables were made using the least-squares method. Data fitting to the exponential model (A = B + e^t/C, where A is the dependent variable, B is one of the constants of the model, t is the time after the start of myocardial cooling, and C is the time constant) used to quantify the FrD and temperature decays was performed with the Levenberg-Marquardt iterative estimation process.

	RESULTS

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Modification of VF by Rapid Myocardial Cooling

During cooling, VF slowed and was finally terminated in all experiments in both series (Figs. 1 and 2). In series 1 termination occurred 33.8 ± 7.3 s after the start of myocardial cooling and the epicardial T_p at the time of termination was 14.4 ± 6.3°C (LV) and 16.5 ± 7.3°C (RV). In series 2, the termination of VF occurred after 28.9 ± 5.4 s and T_p was 15.3 ± 4.7°C (LV) and 15.8 ± 5.6°C (RV).

View larger version (42K): [in this window] [in a new window]   Fig. 1.   Temperature decay and ventricular fibrillation (VF) recordings obtained at baseline, 20 s after the start of myocardial cooling, and during VF termination with 2 electrodes situated in both ventricles, in an experiment in series 1. Also shown are the last 3 activation maps (A, B, and C) before termination of the arrhythmia. Isochrones are drawn at 10-ms intervals. LV, left ventricle; RV, right ventricle; Temp, temperature.

View larger version (28K): [in this window] [in a new window]   Fig. 2.   Power spectrum (B) and VF recordings (A) obtained with 1 of the epicardial electrodes situated in the LV in 1 of the experiments in series 2. Note the progressive decay in dominant frequency (FrD) during myocardial cooling. A2, module; N, recordings and power spectrum obtained every 2 s during myocardial cooling; a.u., arbitrary units.

VV intervals and FrD. Figure 3 shows the mean values of the VV intervals and FrD at baseline, after 20 s, and immediately before VF termination in both experimental series. At baseline VV was smaller and FrD greater in the LV than in the RV (series 1), and in the LV VV was smaller and FrD greater in the subendocardial recordings than in the epicardial recordings (series 2). In both series at baseline the epicardial T_p in both ventricles and the LV endocardial temperature showed no significant differences. During cooling, the VV intervals were seen to prolong, with a decrease in FrD, and the statistical significance of the differences between both ventricles disappeared (series 1), as did the differences between the epicardial and subendocardial recordings (series 2).

View larger version (24K): [in this window] [in a new window]   Fig. 3.   Mean values of the dominant frequency (FrD) and fibrillation intervals (VV intervals) during VF in both ventricles (series 1; A) and in subendocardium, midmyocardium, and epicardium of the LV (series 2; B) obtained at baseline, 20 s after the start of myocardial cooling, and immediately before VF termination (last 2 s). Endoc, subendocardium; Epic, epicardium; Midmyoc, midmyocardium. *P < 0.05 vs. baseline; #P < 0.05 between both ventricles or between subendocardium and epicardium; ns, statistically nonsignificant differences.

The epicardial T_p and the FrD decays during left intraventricular injection of cold Tyrode fit an exponential model in all experiments (Fig. 4). Table 1 shows the mean time constants for both parameters. The differences between the FrD decay constants and those obtained on quantifying T_p decay were not statistically significant, with the exception of RV T_p. The regression straight lines obtained on relating FrD to T_p during cooling were significant both in relation to the epicardial recordings of the LV [FrD = 0.44 T_p(LV)  1.49; r = 0.70; P < 0.0001] and as regards the RV [FrD = 0.39 T_p(RV) + 0.32; r = 0.68; P < 0.0001].

View larger version (24K): [in this window] [in a new window]   Fig. 4.   Data fit to the exponential model of the temperature and FrD decays in both ventricles in 1 of the experiments in series 2. The data for FrD correspond to the recordings of 1 of the electrodes located in the LV epicardium and 1 of the electrodes located in the RV epicardium. t, Time after the start of myocardial cooling.

View this table: [in this window] [in a new window]   Table 1.   Time constants of dominant frequency and temperature decays

Epicardial activation maps. Figure 5 shows the types of epicardial activation maps observed in series 1. At baseline, activation was more complex in the LV than in the RV, for although type II maps predominated in both ventricles, type III maps were more frequent than type I maps in the LV, whereas the opposite applied in the RV (P < 0.0001). Twenty seconds after the start of myocardial cooling, the LV showed a decrease in the number of type III maps and a percent increase in type I maps. The differences between the two ventricles were not statistically significant. On performing analysis in the 2 s preceding VF termination, the most frequent maps were seen to be type I (69% in the LV and 62% in the RV), with a lesser incidence of type II maps and a very limited presence of type III maps.

View larger version (41K): [in this window] [in a new window]   Fig. 5.   Types of activation maps according to their complexity obtained at baseline, 20 s after the start of myocardial cooling, and before termination of the arrhythmia (last 2 s) in both ventricles in series 1. Total no. of maps analyzed (n) and no. of each type of activation maps are indicated. *P < 0.05. T-I, type I maps; T-II, type II maps; T-III, type III maps.

Figure 6 shows the percentages of maps with epicardial breakthrough or complete reentry patterns. At baseline the maps with epicardial breakthrough patterns were significantly more frequent in the LV than in the RV, whereas the percentage of maps exhibiting complete reentry showed no statistically significant differences between the two ventricles. Twenty seconds later the percentages of maps with evidence of epicardial breakthrough were similar to those recorded at baseline, and such maps were also significantly more frequent in the LV than in the RV. Before VF termination the number of maps with evidence of epicardial breakthrough decreased, and no significant differences were observed between the two ventricles. Complete reentry maps practically disappeared from the recordings obtained before VF termination.

View larger version (22K): [in this window] [in a new window]   Fig. 6.   Activation maps with epicardial breakthrough (A) or complete reentry (B) patterns in both ventricles in series 1. n, No. of activation maps analyzed at baseline, 20 s after the start of myocardial cooling, and immediately before VF termination (last 2 s). *P < 0.05 vs. baseline; #P < 0.05 between both ventricles.

Analysis of Moment of VF Termination

In series 1 the latest activation was recorded in the LV in eight experiments, and in these cases the mean of the differences between the latest activation recorded in each ventricle was 100 ± 73 ms. In two experiments termination was practically simultaneous, and in only one case did it occur first in the LV. In series 2 the latest activation was recorded in the LV in nine experiments (mean of the differences = 133 ± 38 ms), and in one case termination was simultaneous in both ventricles. In this series the latest LV activation was recorded in the epicardium in four experiments (mean epicardium-subendocardium difference = 31 ± 12 ms), in the subendocardium in another four experiments (mean subendocardium-epicardium difference = 19 ± 4 ms), and simultaneously in both in two experiments. Analysis of the last activation map during termination of the arrhythmia (Figs. 7 and 8) showed the presence in the LV of only one wave front in seven experiments and of two simultaneous wave fronts in four experiments. Seven maps (64%) showed one or both wave fronts to extinguish within the explored region, without the recording of myocardial activation after extinction. In the RV the activation map at the time of VF termination showed a single wave front in nine experiments, two wave fronts in one experiment, and three wave fronts in another experiment. Four maps (36%) showed wave front extinction within the explored region. Conduction velocity during VF was 49.2 ± 13.2 (LV) and 50.1 ± 4.9 (RV) cm/s at baseline and decreased significantly during hypothermia. Twenty seconds after myocardial cooling was started, conduction velocity was 29.2 ± 8.2 cm/s in the LV (P < 0.05) and 34.1 ± 7.2 cm/s in the RV (P < 0.05), whereas the values before VF termination were 19.2 ± 4.8 cm/s in the LV (P < 0.0001) and 23.0 ± 6.3 cm/s in the RV (P < 0.0001).

View larger version (57K): [in this window] [in a new window]   Fig. 7.   Consecutive activation maps obtained in both ventricles during VF termination in 2 different experiments. Top: in the LV in cycles A and B, a wave front is seen that after turning anticlockwise is blocked in the mapped region, whereas in cycle C the wave front travels the entire explored region without block. The same phenomenon is seen in cycles A and C corresponding to the RV, whereas in cycle B a wave front is seen to extinguish after rotating anticlockwise. Bottom: maps corresponding to both ventricles show a single wave front traveling the entire mapped region. In the LV, conduction is seen to slow to a greater extent in the upper region of the explored area. Isochrones are drawn at 10-ms intervals.

View larger version (33K): [in this window] [in a new window]   Fig. 8.   Last activation maps obtained in both ventricles. The 3 consecutive maps in the LV (right) show extinction of the wave fronts occurring in the upper portion of the mapped region in cycle A, in the midzone in cycle B, and after rotating clockwise in cycle C. In the RV, 2 colliding wave fronts are seen (cycles A and B), whereas in the last cycle a single wave front travels the mapped region without block. Left: recordings corresponding to the electrodes indicated in the activation maps, where conduction block is seen at different levels in the mapped region of the LV. Isochrones are drawn at 10-ms intervals.

Cardiac Rhythm After VF Termination

In most experiments (76%), VF termination was followed by a slow sinus rhythm with progressively increasing cycles until reaching values of ~2 s or giving rise to a period of asystole with an average duration of 12.2 ± 8.6 s (Fig. 9). Maximum bradycardia or asystole occurred 16.2 ± 8.6 s after VF termination, followed by sinus rhythm restoration at progressively increasing frequencies. Acceleration of the sinus rhythm occurred 27.5 ± 12.8 s after VF termination, reaching cycles similar to those previously recorded after 125.1 ± 35.0 scoinciding with the recovery of myocardial temperature. In the remaining 24% of experiments FV termination was directly followed by a period of asystole without atrial or ventricular electrical activity and with an average duration of 17.1 ± 9.2 s. This was in turn followed by the restoration of sinus rhythm at progressively shorter cycles until values similar to those observed at baseline were obtained.

View larger version (14K): [in this window] [in a new window]   Fig. 9.   Recordings obtained after VF termination with 1 electrode situated in the LV, in an experiment in series 2. After VF termination, sinus rhythm (SR) is observed with progressively longer cycles. Maximum bradycardia occurs 27 s after VF termination, after which acceleration of the sinus rhythm begins. The recordings obtained 60 s after VF termination are also shown.

Myocardial Cooling by Injecting Cold Tyrode into Aorta (Series 1' and 2')

As in the previous experimental series, during cooling VF slowed and terminated in all experiments. The time elapsed to VF termination and the time constants of the T_p and FrD decays were significantly greater than on injection of the cold Tyrode into the LV (Table 2), and the epicardial T_p of both ventricles at the time of VF termination was similar to that reached in series 1 and 2. Table 3 shows the mean VV intervals and FrD at baseline, 20 s after injection of cold Tyrode into the aorta was started, and immediately before VF termination. At baseline, and in the same way as in series 1 and 2, significant differences were seen between LV and RV and between the epicardium and subendocardium, FV being faster in the LV and in the subendocardium. Twenty seconds after injection of cold Tyrode was started, slowing of the arrhythmia was less pronounced than in the previous series, and, unlike in series 2, the significant differences between the subendocardium and epicardium persisted in series 2'. These differences in turn disappeared in the moments before termination of the arrhythmia. The regression straight lines obtained on relating FrD to T_p during cooling also were significant [FrD(LV) = 0.43 T_p(LV) 1.63 (r = 0.79; P < 0.0001); FrD(RV) = 0.40 T_p(RV) + 0.51 (r = 0.65; P < 0.0001)].

View this table: [in this window] [in a new window]   Table 2.   Time to VF termination, epicardial temperature at moment of VF termination, and time constants of FrD and Tp decays obtained when cold Tyrode was injected into aorta

View this table: [in this window] [in a new window]   Table 3.   VV intervals and FrD obtained in series 1' and 2' at baseline, 20 s after start of myocardial cooling, and in the 2 s preceding VF termination

The latest activation was recorded in the LV in all experiments, except in two experiments belonging to both series in which it was recorded simultaneously in both ventricles. Of the eight experiments in series 2', the latest activation in the LV occurred in the epicardium in three experiments, in the subendocardium in another three experiments, and simultaneously in both in two experiments. Conduction velocity was significantly decreased before VF termination [LV = 22.9 ± 8.1 vs. 54.9 ± 10.2 cm/s at baseline (P < 0.0001); RV = 24.7 ± 8.8 vs. 53.5 ± 8.8 cm/s at baseline (P < 0.0001)]. The last activation map in series 1' showed only one wave front in the LV in seven experiments and two simultaneous wave fronts in the remaining experiment. The results in the RV were similar. The last activation map showed wave front extinction in six experiments in the LV and in two experiments in the RV.

	DISCUSSION

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The main findings of this study are as follows. 1) During rapid myocardial cooling, temperature and VF activation frequency are significantly correlated and the arrhythmia persists until the temperature decreases to <20°C. 2) The decay in both temperature and FrD fits an exponential model with similar time constants in the LV. 3) Termination of VF occurs preferentially in the LV and is associated with slowing of conduction, extinction of wave fronts, and a decrease in the complexity of the epicardial activation maps.

Effects of Acute Decrease of Myocardial Temperature on VF Activation Patterns

The present study found that myocardial cooling produces a slowing of VF, with a linear correlation between VF activation frequency and myocardial temperature. The activation frequency during VF is related to both the ventricular refractory periods and the wavelength, although to a greater extent to refractoriness (5). Hypothermia increases the ventricular refractory periods (10, 20, 28, 31), as a result of which a slowing of the arrhythmia would be associated with an increase in this parameter. Myocardial cooling also decreases the conduction velocity (19, 27, 28, 31). Consequently, variations in wave length depend on the relation between the changes in its two determining parameters; if the effects on refractoriness predominate, the wave length increases, as has been demonstrated at low temperatures in isolated atrial preparations (26). We also found that during myocardial cooling the complexity of the VF activation patterns decreases, particularly in the moments before termination of the arrhythmia. Wave length prolongation may be implicated in the activation map simplification observed during myocardial cooling. However, it was found (5) that opposing changes in refractoriness or wave length can reduce ventricular activation complexity during VF. Thus consideration should be given to other factors such as the effects on the excitable gap (35) or on the action potential duration restitution curve (17, 23, 32, 33), which can be implicated in the reduction of VF complexity. The results obtained are compatible with an increase in both the wave length and the excitable gap before termination of the arrhythmia, because the decrease in conduction velocity (~60%) is smaller in magnitude than the lengthening of the VF cycle length (>400%) and the reported increases in refractoriness or action potential duration during cooling are of lesser magnitude (1, 2, 10, 28). The marked increase in ventricular cycle length before termination of the arrhythmia would be related to the delay in activation of zones where refractoriness is shorter than the wave front arriving time, as has been postulated to account for widening of the excitable gap during pharmacological cardioversion of atrial fibrillation (34, 35).

Termination of VF During Rapid Myocardial Cooling

Termination of VF preferentially occurred in the LV and has been associated with slowing of conduction, extinction of wave fronts, and a decrease in the complexity of the epicardial activation maps. Another phenomenon observed was the disappearance of the reported differences in activation between the two ventricles (13, 24) and between the epicardium and subendocardium. Preferential termination in the LV may be due to a number of considerations. 1) Cold perfusate was injected directly into the LV, and in the initial seconds, before the cold perfusate reached the whole heart via coronary perfusion, temperature gradients may be established that do not exist at baseline between the LV endocardium and pericardium and between the epicardium of the two ventricles. However, at the time of VF termination no significant differences were found in the epicardial T_p of the two ventricles. On the other hand, similar results were obtained when cold Tyrode was injected into the aorta, although both myocardial temperature decay and arrhythmia slowing to extinction were slower. 2) The maintenance of VF is due to activation in the LV, with RV activation being dependent on the latter. The maintenance of VF has been explained by some authors in terms of the existence of fibrillatory conduction from faster activation zones, which would maintain activation of the rest of the myocardium (3, 13). In the present study, before VF termination we observed wave front extinction and occasionally patterns of intermittent conduction block (Fig. 8). The existence of wave fronts that extinguish indicates conduction depression and difficulties in effective impulse transmission during myocardial cooling. Regardless of the existence of rapid activation foci that would maintain fibrillation until its activity ceases, the observed conduction depression appears to support the role played in arrhythmia termination by a strong reduction of the safety factor for conduction at myocardial temperatures below 20°C. 3) Finally, the preferential termination of the arrhythmia in the LV could reflect different sensitivities to temperature change of the ionic mechanisms implicated in the heterogeneity of the electrophysiological properties of the myocardial cells (13).

Limitations

The mapping electrodes used in the present study did not encompass the entire epicardial surface of both ventricles, and the number of electrodes used to record transmural activation was limited. For this reason, it is not possible to precisely determine the location and characteristics of the last zone activated during VF termination. On the other hand, the decrease in VF activation pattern complexity during myocardial cooling precludes indirect determination of ventricular refractoriness based on the analysis of the VF activation maps (5). No direct techniques have been used for determining refractoriness during VF such as those employed during atrial fibrillation (35); for this reason, no information has been provided concerning duration of the wave length and the excitable gaps during myocardial cooling.

	ACKNOWLEDGEMENTS

This work was supported in part by a grant from the Spanish Society of Cardiology.

	FOOTNOTES

Address for reprint requests and other correspondence: F. J. Chorro, Servicio de Cardiología, Hospital Clínico Universitario, Avda. Blasco Ibañez 17, 46010 Valencia, Spain (E-mail: Francisco.J.Chorro{at}uv.es).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

10.1152/ajpheart.00207.2002

Received 11 March 2002; accepted in final form 5 August 2002.

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