Changing Of Global Electrophysiology Of Left Ventricular Endocardium And Mechanism Of Ventricular Fibrillation During Acute Ischemia

ObjectiveVentricular fibrillation (VF) is the most common arrhythmia that directly leads to sudden cardiac death. Despite years of intensive research, the mechanism of VF remains poorly understood. From a conceptual standpoint, treatment of VF has advanced little since the development of electrical defibrillation in the 1950s. Although implantable cardioverter-defibrillator can save many lives , the expensive prices limits it's extensive using. Investigating the mechanism of VF, especially during acute myocardial infraction, has many important significance. During acute ischemia, the changing of myocardial electrophysiology is the bases of arrhythmia. Most of the researchs about the changing of myocardial electrophysiology are all localized to several specific regions in the ventricles. To date, there has been little in vivo, whole-heart analysis performed. The static tissue heterogeneity, such as local structure and fixed electrophysiological dispersion during acute ischemia, had been widely investigated as a predictor of VF. But recently, more and more evidences indicate that dynamic factors operate synergistically with tissue heterogeneity, as well as among themselves, to promote VF. In this article , with noncontact mapping system, we first investigate the influence of acute ischemia on global repolarization dispersion and ARI restitution property in the left ventricular endocarium and mapping the conduction of waves in the initial phase of VF, to explore the possible mechanism of VF.Methods1 .Lab procedureIn our study, 10 adult mongrel dogs of either sex, weighing 25 to 30 kg, were intubated, mechanically ventilated, and anesthetized with 3% pentobarbital sodium ( 1mL/kg) intraperitoneal injection .The MEA and an ablation catheter were introduced under fluoroscopic guidance from the left and right femoral artery via the retrograde transaortic route into the left ventricle. By dragging the ablation catheter along the endocardial surface, a 3-dimensional geometry of the ventricle was determined. A pacing catheter was positioned at the right ventricular apex from the right femoral vein. Once catheters were placed for mapping, left lateral thoracotomy was performed, and the heart was suspended in a pericardial cradle. Programmed stimulus of S1 S1 and S1S2 were performed to obtain electrophysiological parameters. The mid LAD was isolated and occluded for 30 minutes to produce acute ischemia. After the occlusion period, the same stimulus of S1S1 and S1S2 were performed again to obtain the changed parameters. Then VF was induced by burst pacing, the initial 10-15 seconds of VF were recorded. A rescue shock (15-30J) was delivered to convert VF into simus rhythm after acquiring VF data. At least 5 minutes lapsed between episodes of VF.2.The measurement of electrophysiological parametersA total of 13 regions were analyzed from each ventricle. AT,ARI and RT were measured from reconstructed unipolar electrograms. AT was measured from onset of pacing to the time of dV/dtmin of the local QRS complex. ARI was defined as the interval between AT and RT. The RT was measured at the dV/dtmax for the negative T-wave, the dV/dtmin of the positive T-wave, and at the mean time between dV/dtmax and dV/dtmin for the biphasic T-wave. The difference between the maximum and minimum of AT,ARI and RT is the dispersion of these parameters. DI was measured from the end of RT of the preceding beat to the AT of the following beat. The ARI restitution curves were determined by plotting local ARIs at specific sites against preceding DI. The maximum slope for each restitution curve was fitted using the overlapping leastsquares linear segments.3. Analysis of ventricular fibrillationEpisodes of VF were analysed on the basis of the characteristics of activation in the isopotential movies and isochronal maps, the location of spiral waves was identified and the dominant frequency of different regions was measured. 4. Statistic analysisThe SPSS13.0 software was employed to analyse the date. P<0.05 was considered as statistical significanceResults1. The Feature of electrophysiological parameters before ischemia Repolarization gradients exist over the left ventricular endocardium in normal.The average of ARId was 42±8ms. Because AT and ARI were negatively correlated, the dispersion of RT was smaller than ARI; The slope of restitution curves descend gradually from the apex to the basal, the overall restitution slope of the left ventricle endocardium was <1, the mean maximum slope was 0.74±0.16. But in several canines, the maximum restitution slope was>1 in the septum or apex .2. The change of repolarization dispersion after ischemiaAfter the ligation of LAD 30 min , AT delayed(from23±2ms to 73±18ms, p<0.01) and ARI decreased ,the negative correlation between AT and ARI disappeard in ischemic myocardium. AT and ARI have no change in non-ischemic regions. Repolarization dispersions increased significantly (P<0.01) between ischemic and non-ischemic regions.3. The change of restitution curveIn ischemic regions, restitution curve flatten and the maximum slope decrease significantly; but in some non-ischemic regions(the basal septum and outflow tract), the steepness of the restitution curve increased and the maximum slope>1 (p<0.05) .4. The features of spiral waveSpiral waves were detected at every episode of the initial VF. The lifespan is transient, most of the spiral waves lasted <1 rotation. Usually only a spiral wave occures in one heart beat, occasionally two or more spiral waves were detected simultaneously in different regions. The cores of initiated spiral waves tended to cluster at two specific regions. One was the ischemic regions , the other was the basal septum and the outflow tract of LV. The endocardium of the free walls were activated by large and coheren wavefronts. 5. The feature of VF frequencyIn non-ischemic regions, the mean rotation period of spiral waves is 41.2±18.6ms, the mean frequency of VF is 11.7±1.3 Hz; hi ischemic regions, the mean rotation period of spiral waves is 74.3±22.8ms, the mean frequency of VF is 8.9±1.2Hz. There is significant difference. (P < 0. 05)Conclusions(1) The delayed AT and decreased ARI are all important in increasing the dispersions of ventricular endocardium repolarization during acute ischemia.(2) The dynamic factors of ischemic and non-ischemic myocardium are all changed during acute ischemia. The slope of APD restitution curve in specific non-ischemic regions increased significantly, the maximum slope >1.(3) Spiral wave activation was one of the main features of VF in left ventricular endocardium during acute ischemia. Both ischemic and non- ischemic regions are all important in contributing the creating of spiral waves .The features of spiral waves and frequency of VF indicate that two types of VF coexist during acute regional ischemia.