Both Purkinje Cells and Left Ventricular Posteroseptal Reentry Contribute to the Maintenance of Ventricular Fibrillation in Open-Chest Dogs and Swine  Effects of Catheter Ablation and the Ventricular Cut-and-Sew Operation

Background: Ventricular fibrillation (VF) during prolonged (>5 min) global ischemia (GI) could be due to repetitive endocardial focal discharges (REFDs). This hypothesis was tested in isolated rabbit hearts. Methods and Results: With optical mapping, simultaneous endocardial (left ventricle, LV) and epicardial (both ventricles) activations during VF with prolonged GI were studied (protocol I, 8 hearts). Lugol solution was applied to the LV endocardium in additional 5 hearts after 5-min GI (protocol II). During prolonged GI, sustained VF (>30 s) was successfully induced in 7 protocol I hearts. The dominant frequency of summed optical signals at the LV endocardium was higher than at the epicardium (P<0.05). Mapping data showed that after 5-min GI, REFDs were present in >90% for recording time. There were 18 windows of optical recording showing spontaneous VF termination. In 10, once REFDs ceased, the VF episode terminated immediately. Electrical defibrillation was also performed on 3 hearts. Eight shocks showed early VF recurrence after successful defibrillation. REFDs were consistently involved in the initiation period of recurrence. In protocol II, Lugol subendocardial ablation diminished REFD genesis during re-induced VF. These VF episodes were all non-sustained. Conclusions: REFDs at the LV endocardium were important for both VF maintenance and post-shock recurrence during prolonged GI in this model. (Circ J 2009; 73: 1803 -1811

Section: Relationship Of Epicardial Repetitive Activities and Refds Dmentioning

confidence: 62%

Repetitive Endocardial Focal Discharges During Ventricular Fibrillation With Prolonged Global Ischemia in Isolated Rabbit Hearts

Lin

Hsieh

et al. 2009

“…[28][29][30] Fedorov et al reported that hypothermia at 27°C and 17°C results in non-uniform conduction slowing, increased dispersion of repolarization, and shortened WL in isolated rabbit hearts. 28 Using a clinically applicable temperature (30°C), we observed that TH decreased CV, shortened WL, and enhanced APD dispersion and spatial heterogeneity of CT -1 restitution, consistent with the results reported by Harada et al in a 2-dimensional rabbit ventricle at TH (30°C).…”

Section: Electrophysiological Properties During Th (30°c)mentioning

confidence: 99%

Therapeutic Hypothermia (30.DEG.C) Enhances Arrhythmogenic Substrates, Including Spatially Discordant Alternans, and Facilitates Pacing-Induced Ventricular Fibrillation in Isolated Rabbit Hearts

Hsieh

Lin

et al. 2009

herapeutic hypothermia (TH, 30°C) has decreased intracranial pressure, slowed cerebral metabolic processes, and protected the brain from anoxic injury in animal models and human scenarios. [1][2][3] Recent guidelines also recommend that unconscious adult patients with spontaneous circulation after out-of-hospital ventricular fibrillation (VF) cardiac arrest should be cooled to 32-34°C for 12-24 h. [4][5][6] Although previous studies showed that extreme hypothermia (<29°C) might potentiate the occurrence of lethal ventricular arrhythmia, 7-9 the myocardial substrate properties in the therapeutic range of hypothermia (≥30°C) are not completely understood. Because 30°C is the lowest temperature that has proven to be feasible in clinical practice, 1-3 we chose it to test the ventricular substrate for arrhythmogenesis in the present study.One mechanism for determining the maintenance of VF is its wavefront characteristics during VF. 10,11 Harada et al found that in 2-dimensional rabbit ventricular preparations, TH (30°C) enhanced wavebreaks and regeneration of new spiral waves during VF, facilitating the maintenance of ventricular tachycardia (VT) and VF. 12 While using a clinically appropriate temperature of 32-34°C, they demonstrated that the spiral waves of VT/VF frequently collided and dissipated in favor of self-termination of VT/VF, a different effect from that of TH at 30°C. 12 Whether the wavefront characteristics (ie, wavebreaks) of VF in this 2-dimensional model also occur in 3-dimensional intact hearts at TH (30°C) remains unclear. Cardiac alternans, particularly spatially discordant alternans (SDA), is a key arrhythmogenic factor for ventricular tachyarrhythmia. 13 However, limited information is available regarding cardiac alternans properties during TH (30°C). 14 In this study, using an optical mapping system, we investigated the wavefront characteristics of VF (ie, wavebreaks, spatiotemporal periodicities), cardiac electrophysiological/ alternans properties, and the vulnerability of pacing-induced VF specifically at TH (30°C) in 3-dimensional Langendorffperfused isolated rabbit hearts. We hypothesized that TH (30°C) enhances wavebreaks during VF and S1 pacing, facilitates pacing-induced SDA, and increases the vulnerability of pacing-induced VF. Background: Therapeutic hypothermia (TH, 30°C) protects the brain from hypoxic injury. However, TH may potentiate the occurrence of lethal ventricular fibrillation (VF), although the mechanism remains unclear. The present study explored the hypothesis that TH enhances wavebreaks during VF and S1 pacing, facilitates pacinginduced spatially discordant alternans (SDA), and increases the vulnerability of pacing-induced VF. Methods and Results:Using an optical mapping system, epicardial activations of VF were studied in 7 Langendorff-perfused isolated rabbit hearts at baseline (37°C), TH (30°C), and rewarming (37°C). Action potential duration (APD)/conduction velocity (CV) restitution and APD alternans (n=6 hearts) were determined by S1 pacing at these 3 stages. Duri...

“…The discrepancy in the results among experimental studies may partly be attributable to differences in the size of the heart or to differences in species-related electrophysiological properties of the myocardial tissue. In a recent study by Pak et al, 6 destruction of Purkinje fibers by ablation of the posterior papillary muscle and left ventricular posteroseptum attenuated VF inducibility in both dogs and pigs.…”

Section: Role Of Purkinje Fibers In the Maintenance Of Ventricular Fimentioning

confidence: 91%

“…[2][3][4][5][6] The Purkinje fiber system, which plays a critical role in harmonious myocardial contraction and relaxation via its efficient propagation properties and unique geometrical distribution, 7 is naturally worthy of note when discussing a possible source of VF. Because of the conspicuous heterogeneity in the action potential duration of Purkinje fibers compared with the working myocardium, it is likely that this system offers a substrate for reentry to sustain VF.…”

Section: Article P 1803mentioning

confidence: 99%

Role of Purkinje Fibers in the Maintenance of Ventricular Fibrillation

Murakawa

2009

any experimental and clinical studies on the mechanisms of ventricular fibrillation (VF) have been performed over the past 10 decades. The underlying mechanisms of VF have been discussed from different points of view: initiation and maintenance. It is beyond question that reentry, triggered activity or automaticity initiates VF, but the mechanism of its maintenance is not fully determined. Although the duration from the onset of VF may affect its electrophysiological features, maintenance of VF has been explained by the coexistence of 2 or more unstable multiple wavelets or mother rotors. 1 Article p 1803In recent studies, however, attention has been directed to the role of Purkinje fibers in the initiation and maintenance of VF. 2-6 The Purkinje fiber system, which plays a critical role in harmonious myocardial contraction and relaxation via its efficient propagation properties and unique geometrical distribution, 7 is naturally worthy of note when discussing a possible source of VF. Because of the conspicuous heterogeneity in the action potential duration of Purkinje fibers compared with the working myocardium, it is likely that this system offers a substrate for reentry to sustain VF.The VF threshold (VFT), expressed by the amount of electrical stimulation to induce VF, has been used to quantify the susceptibility of the heart to VF. [8][9][10] Horowitz et al reported a significant difference between endocardial and epicardial VFTs in the left ventricle. 8 They considered that the coexistence of ordinary myocardium with shorter repolarization characteristics and Purkinje fibers with a long refractory period in the endocardium facilitated the induction of VF. Later, Damiano et al attempted to clarify the role of the Purkinje network on ventricular vulnerability. 9 In their study, the baseline VFT was 26±2 mA and increased to 53±6 mA after total ablation of the endocardial surface by applying Lugol's solution. This observation was in agreement with Horowitz's suggestion. In a more recent study using a 3-dimensional model of the ventricles, 2 the Purkinje system was shown to give rise to initial reentry, which led to the establishment of intramyocardial reentry independent of the Purkinje network.Purkinje fibers are known to be so resistant to ischemia that they survive and continue to function even during longlasting VF, 11 which may explain why VF terminates spontaneously in hearts with subendocardial chemical ablation, and suggests that Purkinje fibers play a significant role in the maintenance of VF. 5 Recently, Tabereaux et al investigated the activation pattern during VF. 3 They found that Purkinje fibers are highly active even 10 min after the onset of VF. In addition to retrograde propagation from the working ventricular myocardium to the Purkinje fibers, they noticed antegrade propagation also occurred from the Purkinje fibers to the working ventricular myocardium. This phenomenon supports the hypothesis that Purkinje fibers play an important role in the maintenance of VF, as well as in its initiation.I...