Verapamil reduces incidence of reentry during ventricular fibrillation in pigs

The characteristics of reentrant circuits during short duration ventricular fibrillation (SDVF; 20 s in duration) and the role of Ca++ and rapid-activating delayed rectifier potassium currents during long duration ventricular fibrillation (LDVF; up to 10 min in duration) were investigated using verapamil and sotalol. Activation mapping of the LV epicardium with a 21 × 24 electrode plaque was performed in 12 open-chest pigs. Pigs were given either verapamil (0.136 mg/kg) or sotalol (1.5 mg/kg) and verapamil. Reentry patterns were quantified for SDVF, and, for LDVF, activation patterns were compared with our previously reported control LDVF data. Verapamil significantly increased conduction velocity around the reentrant core by 10% and reduced the reentrant cycle length by 15%, with a net reduction in reentry incidence of 70%. Sotolol had an opposite effect of decreasing the conduction velocity around the core by 6% but increasing the reentrant cycle length by 13%, with a net reduction of reentry incidence of 50%. After 200 s of VF, verapamil significantly slowed wavefront conduction velocity and activation rate compared with control data. Verapamil decreased the incidence of reentry in SDVF by accelerating conduction velocity to increase the likelihood of conduction block, possibly through increased sympathetic tone. The drug slowed activation rate and conduction velocity after 200 s of VF, suggesting that L-type Ca++ channels remain active and may be important in the maintenance of LDVF. Sotalol in addition to verapamil caused no additional antiarrhythmic effect.

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Activation becomes highly organized during long-duration ventricular fibrillation in canine hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01196.2009 ◽

2010 ◽

Vol 298 (6) ◽

pp. H2046-H2053 ◽

Cited By ~ 13

Author(s):

Li Li ◽

Qi Jin ◽

Derek J. Dosdall ◽

Jian Huang ◽

Steven M. Pogwizd ◽

...

Keyword(s):

Ventricular Fibrillation ◽

Conduction Block ◽

Three Dimensional ◽

Left Ventricular ◽

The Body ◽

Long Duration ◽

Surface Ecg ◽

Electrode Matrix ◽

Different Levels

Little is known about the three-dimensional (3-D) intramural activation sequences during long-duration ventricular fibrillation (VF), including the role of the subendocardium and its Purkinje fibers (PFs) in long-duration VF maintenance. Our aim was to explore the mechanism of long-duration VF maintenance with 3-D electrical mapping. We recorded 10 min of electrically induced VF in the left ventricular anterior free wall of six 10-kg, open-chest dogs using a 3-D transmural unipolar electrode matrix (9 × 9 × 6, 2-mm spacing) that allowed us to map intramural activation sequences. At 2.5 ± 1.8 min of VF, although the body surface ECG continued to exhibit a disorganized VF pattern, intramurally a more organized, synchronous activation pattern was first observed [locally synchronized VF (LSVF)]. This pattern occurred one or more times in all dogs and was present 33.4 ± 31.4% of the time during 5–10 min of VF. As opposed to the preceding changing complex activation sequences of VF, during LSVF, wavefronts were large and highly repeatable near the endocardium, first exciting the endocardium almost simultaneously and then rapidly spreading toward the epicardium with different levels of conduction block en route. During LSVF, PF activations always preceded working myocardium activations near the endocardium. In conclusion, long-duration VF in dogs frequently becomes highly organized in the subendocardium, with activation fronts arising in this region and passing intramurally toward the epicardium, even though the surface ECG continues to exhibit a disorganized pattern. PFs appear to play an important role during this stage of VF.

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Intramural optical mapping of Vm and Cai2+ during long-duration ventricular fibrillation in canine hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00426.2011 ◽

2012 ◽

Vol 302 (6) ◽

pp. H1294-H1305 ◽

Cited By ~ 9

Author(s):

Wei Kong ◽

Raymond E. Ideker ◽

Vladimir G. Fast

Keyword(s):

Ventricular Fibrillation ◽

Action Potential ◽

Short Duration ◽

Action Potential Duration ◽

Cycle Length ◽

The Other ◽

Membrane Voltage ◽

Long Duration ◽

Intracellular Ca ◽

Rapid Pacing

Intramural gradients of intracellular Ca2+ (Cai2+) Cai2+ handling, Cai2+ oscillations, and Cai2+ transient (CaT) alternans may be important in long-duration ventricular fibrillation (LDVF). However, previous studies of Cai2+ handling have been limited to recordings from the heart surface during short-duration ventricular fibrillation. To examine whether abnormalities of intramural Cai2+ handling contribute to LDVF, we measured membrane voltage ( Vm) and Cai2+ during pacing and LDVF in six perfused canine hearts using five eight-fiber optrodes. Measurements were grouped into epicardial, midwall, and endocardial layers. We found that during pacing at 350-ms cycle length, CaT duration was slightly longer (by ≃10%) in endocardial layers than in epicardial layers, whereas action potential duration (APD) exhibited no difference. Rapid pacing at 150-ms cycle length caused alternans in both APD (APD-ALT) and CaT amplitude (CaA-ALT) without significant transmural differences. For 93% of optrode recordings, CaA-ALT was transmurally concordant, whereas APD-ALT was either concordant (36%) or discordant (54%), suggesting that APD-ALT was not caused by CaA-ALT. During LDVF, Vm and Cai2+ progressively desynchronized when not every action potential was followed by a CaT. Such desynchronization developed faster in the epicardium than in the other layers. In addition, CaT duration strongly increased (by ∼240% at 5 min of LDVF), whereas APD shortened (by ∼17%). CaT rises always followed Vm upstrokes during pacing and LDVF. In conclusion, the fact that Vm upstrokes always preceded CaTs indicates that spontaneous Cai2+ oscillations in the working myocardium were not likely the reason for LDVF maintenance. Strong Vm-Cai2+ desynchronization and the occurrence of long CaTs during LDVF indicate severely impaired Cai2+ handling and may potentially contribute to LDVF maintenance.

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Exploring the role of pH in modulating the effects of lidocaine in virtual ischemic tissue

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00425.2010 ◽

2010 ◽

Vol 299 (5) ◽

pp. H1615-H1624 ◽

Cited By ~ 8

Author(s):

Karen Cardona ◽

Beatriz Trénor ◽

Germán Moltó ◽

Miguel Martínez ◽

José María Ferrero ◽

...

Keyword(s):

Conduction Velocity ◽

Conduction Block ◽

One Dimensional ◽

Pathological Conditions ◽

Ischemic Tissue ◽

Current Maximum ◽

Acute Regional Ischemia ◽

Present Simulation ◽

Upstroke Velocity

Lidocaine is a class I antiarrhytmic drug that blocks Na+ channels and exists in both neutral and charged forms at a physiological pH. In this work, a mathematical model of pH and the frequency-modulated effects of lidocaine has been developed and incorporated into the Luo-Rudy model of the ventricular action potential. We studied the effects of lidocaine on Na+ current, maximum upstroke velocity, and conduction velocity and demonstrated that a decrease of these parameters was dependent on pH, frequency, and concentration. We also tested the action of lidocaine under pathological conditions. Specifically, we investigated its effects on conduction block under acute regional ischemia. Our results in one-dimensional fiber simulations showed a reduction of the window of block in the presence of lidocaine, thereby highlighting the role of reduced conduction velocity and safe conduction. This reduction may be related to the antifibrillatory effects of the drug by hampering wavefront fragmentation. In bidimensional acute ischemic tissue, lidocaine increased the vulnerable window for reentry and exerted proarrhythmic effects. In conclusion, the present simulation study used a newly formulated model of lidocaine, which considers pH and frequency modulation, and revealed the mechanisms by which lidocaine facilitates the onset of reentries. The results of this study also help to increase our understanding of the potential antifibrillatory effects of the drug.

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Discordant S-T alternans contributes to formation of reentry: a possible mechanism of reperfusion arrhythmia

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.275.1.h116 ◽

1998 ◽

Vol 275 (1) ◽

pp. H116-H121 ◽

Cited By ~ 11

Author(s):

Hidetada Tachibana ◽

Isao Kubota ◽

Michiyasu Yamaki ◽

Tetsu Watanabe ◽

Hitonobu Tomoike

Keyword(s):

Coronary Artery ◽

Ventricular Fibrillation ◽

Conduction Block ◽

Activation Time ◽

Reperfusion Arrhythmia ◽

Open Chest ◽

Life Threatening ◽

Control State ◽

Reentrant Circuit

Although a relationship between S-T alternans and life-threatening arrhythmia has been recognized, the mechanism is poorly understood. We examine the role of S-T alternans in the occurrence of ventricular fibrillation (VF) after reperfusion. The left anterior descending coronary artery was occluded for 20 min and then abruptly reperfused in 12 intravenously anesthetized open-chest dogs. Sixty unipolar epicardial electrograms were recorded during the control state, at the end of occlusion, and after reperfusion. The largest magnitude of S-T alternans among 60 leads was defined as the maximum S-T alternans. Isochronal maps of activation time in paced beat and spontaneous ventricular premature contractions (VPC) were analyzed. After reperfusion, VF ensued in six dogs. The maximum S-T alternans augmented progressively with time after reperfusion until VF occurred. In three dogs with VF, when activation of VPC resulted in conduction block and formed reentry, VF ensued. The conduction block was located between sites of discordant S-T alternans (S-T alternans at adjacent leads was out of phase). These data indicate that discordant S-T alternans relates to VF by facilitating the formation of a reentrant circuit.

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Evolution of activation patterns during long-duration ventricular fibrillation in pigs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00419.2011 ◽

2012 ◽

Vol 302 (4) ◽

pp. H992-H1002 ◽

Cited By ~ 15

Author(s):

Kang-An Cheng ◽

Derek J. Dosdall ◽

Li Li ◽

Jack M. Rogers ◽

Raymond E. Ideker ◽

...

Keyword(s):

Ventricular Fibrillation ◽

Stage Iv ◽

Stage Ii ◽

Electrode Arrays ◽

Activation Patterns ◽

Voltage Change ◽

Activation Rate ◽

Clinical Consequences ◽

S Period

Quantitative analysis has demonstrated five temporal stages of activation during the first 10 min of ventricular fibrillation (VF) in dogs. To determine whether these stages exist in another species, we applied the same analysis to the first 10 min of VF recorded in vivo from two 504-electrode arrays, one each on left anterior and posterior ventricular epicardium in six anesthetized pigs. The following descriptors were continuously quantified: 1) number of wavefronts, 2) wavefront fractionations, 3) wavefront collisions, 4) repeatability, 5) multiplicity index, 6) wavefront conduction velocity, 7) activation rate, 8) mean area activated by the wavefronts, 9) negative peak rate of voltage change, 10) incidence of breakthrough/foci, 11) incidence of block, and 12) incidence of reentry. Cluster analysis of these descriptors divided VF into four stages ( stages i-iv). The values of most descriptors increased during stage i (1–22 s after VF induction), changed quickly to values indicating greater organization during stage ii (23–39 s), decreased steadily during stage iii (40–187 s), and remained relatively unchanged during stage iv (188–600 s). The epicardium still activated during stage iv instead of becoming silent as in dogs. In conclusion, during the first 10 min, VF activation can be divided into four stages in pigs instead of five stages as in dogs. Following a 16-s period during the first minute of VF when activation became more organized, all parameters exhibited progressive decreased organization. Further studies are warranted to determine whether these changes, particularly the increased organization of stage ii, have clinical consequences, such as alteration in defibrillation efficacy.

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Estimated Global Transmural Distribution of Activation Rate and Conduction Block During Porcine and Canine Ventricular Fibrillation

Circulation Research ◽

10.1161/01.res.0000120860.01645.17 ◽

2004 ◽

Vol 94 (6) ◽

pp. 836-842 ◽

Cited By ~ 54

Author(s):

Jonathan C. Newton ◽

William M. Smith ◽

Raymond E. Ideker

Keyword(s):

Ventricular Fibrillation ◽

Conduction Block ◽

Activation Rate

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Estimated Global Epicardial Distribution of Activation Rate and Conduction Block During Porcine Ventricular Fibrillation

Journal of Cardiovascular Electrophysiology ◽

10.1046/j.1540-8167.2002.01035.x ◽

2002 ◽

Vol 13 (10) ◽

pp. 1035-1041 ◽

Cited By ~ 22

Author(s):

JONATHAN C. NEWTON ◽

PHILLIP L. JOHNSON ◽

R. KYLE JUSTICE ◽

WILLIAM M. SMITH ◽

RAYMOND E. IDEKER

Keyword(s):

Ventricular Fibrillation ◽

Conduction Block ◽

Activation Rate

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Abstract 2020: The Effect of Global Ischemia and Reperfusion on Long Duration of Human Ventricular Fibrillation: A Multi-Electrode Mapping Study

Circulation ◽

10.1161/circ.116.suppl_16.ii_437-a ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Stephane Masse ◽

Adel K Hamad ◽

Rajesh Dhopeshwarkar ◽

Salem Al-Kaabi ◽

John Asta ◽

...

Keyword(s):

Ventricular Fibrillation ◽

Myocardial Ischemia ◽

Rest Period ◽

Dominant Frequency ◽

Recent Change ◽

Global Ischemia ◽

Long Duration ◽

Activation Rate ◽

Most Significant Change ◽

Activation Rates

Introduction: The most significant change to the latest AHA CPR guidelines is the recommendation of CPR first followed by defibrillation, for un-witnessed arrests. We tested the hypothesis that global myocardial ischemia during ventricular fibrillation (VF) decreases activation rate and short duration of reperfusion would normalize activation rates. Methods: We studied 6 Langendorff perfused human hearts which were explanted from cardiomyopathic patients who underwent transplantation. Tyrode solution was used for perfusion and flow was maintained at 0.9 to 1.1 ml/g/min. Multi-electrode mapping was performed for the entire epicardium (112 electrodes sock array) and the LV endocardium (112 electrodes balloon array). VF was induced by applying a 9-volt battery on the epicardium. As soon as the VF episode was induced, perfusion was turned off for 200 seconds mimicking global ischemia. At the end of this period the perfusion system was turned back on at a flow similar to baseline for an additional 140 seconds, mimicking a state of reperfusion. The hearts were then defibrillated and this protocol was repeated twice after a rest period of 5 minutes. For the analysis, 20 s electrograms located on the LV freewall (both endo and epi) were recorded at t = 0, 90, 180, 260 and 320s, for a total of 11520 electrograms. Local Activation Rates (LAR) for each electrogram was determined as the dominant frequency (DF) corresponding to the highest value in the power spectrum between 1.5 and 8 Hz. Results: Activation rate decreased from 4.962±0.020 Hz to 3.704±0.022 Hz (p<0.0001) during the 200 seconds of global ischemia. During the 140 seconds of reperfusion the activation rate increased to 4.882±0.024 Hz (p<0.0001). This value was comparable to what was measured at the onset of VF (p = 0.011). These changes of rates were similar for both endocardium and epicardium data (p = 0.0236). Conclusions: During long episodes of human VF, global myocardial ischemia leads to slowing of activation rate on the epicardium and endocardium. Two minutes of re-perfusion leads to reversal of this effect. These findings may support the recent change in CPR guidelines.

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Purkinje involvement in arrhythmias after coronary artery reperfusion

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00227.2001 ◽

2002 ◽

Vol 282 (4) ◽

pp. H1189-H1196 ◽

Cited By ~ 16

Author(s):

David O. Arnar ◽

James B. Martins

Keyword(s):

Ventricular Tachycardia ◽

Coronary Artery ◽

Ventricular Fibrillation ◽

Cycle Length ◽

Ischemic Myocardium ◽

Risk Zone ◽

Purkinje System ◽

Mean Cycle

Previous studies have indicated that the endocardium may be responsible for a large portion of ventricular tachycardia (VT) seen with reperfusion of ischemic myocardium. To evaluate the role of the Purkinje system in nonreentrant VT arising from the endocardium after reperfusion, the anterior descending coronary artery was occluded for 20 min and then reperfused in 23 dogs after instrumentation of the risk zone with 21 multipolar plunge needles. VT with focal Purkinje origin was defined as a focal endocardial VT with Purkinje potentials recorded before the earliest endocardial myopotential. A total of 19 VTs (mean cycle length 214 ± 2 ms) were observed with 11 (58%) having focal Purkinje origin. Fifty-eight percent of the VTs degenerated to ventricular fibrillation, with occurrences of two or more independent foci per complex (seen in 7 of 11 compared with 1 of 8 nonsustained VTs). In conclusion, these data show that Purkinje tissue may be important in the genesis of reperfusion VT.

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