Intracellular Calcium and Vulnerability to Fibrillation and Defibrillation in Langendorff-Perfused Rabbit Ventricles

Hwang, Gyo Seung; Hayashi, Hideki; Tang, Liang; Ogawa, Masahiro; Hernandez, Heidy; Tan, Alex Y.; Li, Hongmei; Karagueuzian, Hrayr S.; Weiss, James N.; Lin, Shien Fong; Chen, Peng Sheng

doi:10.1161/circulationaha.106.630509

Cited by 46 publications

(47 citation statements)

References 27 publications

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“…For one thing, spatiotemporal variation of AP shape may increase heterogeneity of the responses to virtual electrode polarization (9,11,15), thus increasing a chance of forming new reentrant waves postshock. In addition, the ischemia-specific AP instability may be an indicator of destabilized Ca i dynamics (21), which in itself may be a factor of defibrillation success or failure (22). Further studies are required to test these possible mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Three distinct phases of VF during global ischemia in the isolated blood-perfused pig heart

Huízar¹,

Warren²,

Shvedko³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Zaitsev AV. Three distinct phases of VF during global ischemia in the isolated blood-perfused pig heart. Am J Physiol Heart Circ Physiol 293: H1617-H1628, 2007. First published June 1, 2007; doi:10.1152/ajpheart.00130.2007.-Changes in ventricular fibrillation (VF) organization occurring after the onset of global ischemia are relevant to defibrillation and survival but remain poorly understood. We hypothesized that ischemia-specific dynamic instability of the action potential (AP) causes a loss of spatiotemporal periodicity of propagation and broadening of the electrocardiogram (ECG) frequency spectrum during VF in the ischemic myocardium. We recorded voltage-sensitive fluorescence of di-4-ANEPPS (anterior left ventricle, 35 ϫ 35 mm, 64 ϫ 64 pixels) and the volumeconducted ECG in six blood-perfused hearts during 10 min of VF and global ischemia. We used coefficient of variation (CV) to estimate variability of AP amplitude, AP duration, and diastolic interval (CV-APA, CV-APD, and CV-DI, respectively). We computed excitation median frequency (Median_F), spectral width of the AP and ECG (SpW-AP and SpW-ECG, respectively), wavebreak incidence (WBI), and recurrence of propagation direction (RPD). We found three distinct phases of local VF dynamics: "relatively periodic" (Յ1 min, high Median_F, moderate AP variability, high WBI, low RPD), "highly periodic" (1-2 min, reduced Median_F, low AP variability, low WBI, high RPD), and "aperiodic" (3-10 min, low Median_F, high AP variability, high WBI, low RPD). In one experiment, spontaneous conversion from the aperiodic to the highly periodic phase occurred after 5 min of ischemia. The SpW-ECG was correlated with SpW-AP, CV-APD, and CV-APA. We conclude that 1) at least three distinct phases of VF dynamics are present in our model, and 2) the newly described aperiodic phase is related to ischemia-specific dynamic instability of the AP shape, which underlies broadening of the ECG spectrum during VF evolution. ventricular fibrillation; action potential; electrocardiogram ONE IMPORTANT DECISION that an emergency care professional faces at the scene of cardiac arrest is whether to initiate cardiopulmonary resuscitation (CPR) before the application of a shock, or to defibrillate first. Population studies indicate that the "CPR first" strategy improves survival if the ventricular fibrillation (VF) duration exceeds 3-4 min ("circulatory phase") but not at the earlier "electrical" phase of VF (18). This observation motivated recent studies aimed at estimating VF duration based on the structure and spectral content of the electrocardiogram (ECG) waveform (6, 27, 34). Furthermore, various quantitative measures of "order" in the ECG waveform can predict the likelihood of rescue shock success, restoration of circulation, and survival to hospital discharge (4, 6). However, the relationship between the structure of the ECG waveform and the spatiotemporal dynamics of the fibrillatory waves in the myocardium remains unknown.VF organization evolves naturally after its onset as a result of glo...

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Section: Discussionmentioning

confidence: 99%

Three distinct phases of VF during global ischemia in the isolated blood-perfused pig heart

Huízar¹,

Warren²,

Shvedko³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…24 Additionally, spontaneous calcium release and the formation of calcium sinkholes after defibrillation shocks have been proposed to decrease the chance of successful defibrillation shocks. 25 The stabilization of RyR2 and the suppression of these local calcium release events during VF can potentially break the vicious cycle of long-duration VF and [Ca] 2+ i overload and enhance defibrillation success as proposed by other groups. 5,24,25 Purkinje fiber activation is reported to be responsible for postshock arrhythmias and unsuccessful shocks after VF both in experimental 25,26 and computer modeling 27 studies.…”

Section: Dantrolene Enhances Defibrillation Successmentioning

confidence: 96%

“…25 The stabilization of RyR2 and the suppression of these local calcium release events during VF can potentially break the vicious cycle of long-duration VF and [Ca] 2+ i overload and enhance defibrillation success as proposed by other groups. 5,24,25 Purkinje fiber activation is reported to be responsible for postshock arrhythmias and unsuccessful shocks after VF both in experimental 25,26 and computer modeling 27 studies. In our study, dantrolene suppressed after-depolarizations and triggered activity in Purkinje fibers (presumably by suppressing the afore-mentioned diastolic SCaEs) and, therefore, prevented APD formation and the propagation in Purkinje fibers after fast pacing and VF (Figure 4).…”

Section: Dantrolene Enhances Defibrillation Successmentioning

confidence: 96%

Dantrolene Improves Survival After Ventricular Fibrillation by Mitigating Impaired Calcium Handling in Animal Models

et al. 2014

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Background— Resistant ventricular fibrillation, refibrillation. and diminished myocardial contractility are important factors leading to poor survival after cardiac arrest. We hypothesized that dantrolene improves survival after ventricular fibrillation (VF) by rectifying the calcium dysregulation caused by VF. Methods and Results— VF was induced in 26 Yorkshire pigs for 4 minutes. Cardiopulmonary resuscitation was then commenced for 3 minutes, and dantrolene or isotonic saline was infused at the onset of cardiopulmonary resuscitation. Animals were defibrillated and observed for 30 minutes. To study the effect of VF on calcium handling and its modulation by dantrolene, hearts from 14 New Zealand rabbits were Langendorff-perfused. The inducibility of VF after dantrolene administration was documented. Optical mapping was performed to evaluate diastolic spontaneous calcium elevations as a measure of cytosolic calcium leak. The sustained return of spontaneous circulation (systolic blood pressure ≥60 mm Hg) was achieved in 85% of the dantrolene group in comparison with 39% of controls ( P =0.02). return of spontaneous circulation was achieved earlier in dantrolene-treated pigs after successful defibrillation (21±6 s versus 181±57 s in controls, P =0.005). The median number of refibrillation episodes was lower in the dantrolene group (0 versus 1, P =0.04). In isolated rabbit hearts, the successful induction of VF was achieved in 83% of attempts in controls versus 41% in dantrolene-treated hearts ( P =0.007). VF caused diastolic calcium leaks in the form of spontaneous calcium elevations. Administration of 20 μmol/L dantrolene significantly decreased spontaneous calcium elevation amplitude versus controls. (0.024±0.013 versus 0.12±0.02 arbitrary unit [200-ms cycle length], P =0.001). Conclusions— Dantrolene infusion during cardiopulmonary resuscitation facilitates successful defibrillation, improves hemodynamics postdefibrillation, decreases refibrillation, and thus improves survival after cardiac arrest. The effects are mediated through normalizing VF-induced dysfunctional calcium cycling.

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“…Understanding the origins of the isoelectric window is thus of great importance for uncovering the mechanisms of defibrillation failure. Various hypothesis have been proposed for the existence of the isoelectric window, including virtual electrodeinduced propagated graded response (Trayanova et al, 2003), calcium sinkholes (Hwang et al, 2006), and activations emanating from Purkinje fibers (Dosdall et al, 2007); however, the mechanisms responsible for it remain inconclusive. In this context, we hypothesized that submerged "tunnel propagation" of postshock activation (PA) through shock-induced intramural excitable areas underlies both fibrillation induction and failed defibrillation by shocks as well as the existence of an isoelectric window.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Defibrillation Failure

Ashihara¹,

Constantino²,

Trayanova³

2011

Cardiac Defibrillation - Mechanisms, Challenges and Implications

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Intracellular Calcium and Vulnerability to Fibrillation and Defibrillation in Langendorff-Perfused Rabbit Ventricles

Cited by 46 publications

References 27 publications

Three distinct phases of VF during global ischemia in the isolated blood-perfused pig heart

Three distinct phases of VF during global ischemia in the isolated blood-perfused pig heart

Dantrolene Improves Survival After Ventricular Fibrillation by Mitigating Impaired Calcium Handling in Animal Models

Mechanisms of Defibrillation Failure

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