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Background: While reentry within the ventricular myocardium (VM) is responsible for the maintenance of short-duration ventricular fibrillation (SDVF; VF duration <1 minute), Purkinje fibers (PFs) are important in the maintenance of long-duration ventricular fibrillation (LDVF; VF duration >1 minute).Objective: The purpose of this study was to test the hypothesis that the mechanisms of defibrillation may also be different for SDVF and LDVF.Methods: A multielectrode basket catheter was deployed in the left ventricle of eight beagles. External defibrillation shocks were delivered with a ramp-up protocol after SDVF (20 seconds) and LDVF (150 seconds). Earliest VM and PF activations were identified after the highest energy shock that failed to terminate VF and the successful shock.Results: Defibrillation was successful after 36 +/- 12 and 181 +/- 14 seconds for SDVF and LDVF, respectively. The time after shock delivery until earliest activation was detected for failed shocks and was significantly longer after LDVF (138.7 +/- 24.1 ms) than after SDVF (75.6 +/- 8.7 ms). Earliest postshock activation after SDVF typically initiated in the VM (14 of 16 episodes), while it always initiated in the PF (16 of 16 episodes) after LDVF. Sites of earliest activity during sinus rhythm correlated with sites of earliest postshock activation for PF-led cycles but not for VM-led cycles.Conclusion: Earliest recorded postshock activation is in the Purkinje system after LDVF but not after SDVF. This difference raises the possibility that the optimal defibrillation strategy is different for SDVF and LDVF. [ABSTRACT FROM AUTHOR]

Background: Knowledge of transmural V(m) changes is important for understanding the mechanism of long-duration ventricular fibrillation (LDVF).Objective: The purpose of this study was to measure transmural V(m) changes during LDVF.Methods: V(m) was recorded optically at up to 8 transmural points separated by 1.5 mm in the left ventricle of Langendorff-perfused canine hearts (n = 6) using a bundle of optical fibers (optrode) during 10 minutes of LDVF followed by 3 minutes of VF with reperfusion. Measurements were grouped into 4 layers: epicardium, subepicardium, midwall, and subendocardium.Results: Activation rates (ARs) and action potential durations (APDs) decreased, whereas diastolic intervals (DIs) increased during LDVF in all transmural layers (P < .05). After approximately 3 minutes of LDVF, ARs were faster and DIs shorter in the midwall and subendocardium than in the epicardium and subepicardium (P < .05). Activations persisted at the subendocardium but disappeared from other layers after approximately 8 minutes of VF in the majority of hearts. There were no transmural differences in APD during LDVF or during pacing before and after LDVF (P > .05). Restitution plots showed no functional relationship between APD and DI in any layer at any stage of LDVF. Partial reperfusion during VF for 3 minutes restored transmural synchronicity of activation and eliminated gradients in activation parameters.Conclusion: V(m) dynamics evolve differently at different transmural layers. The subendocardium maintains persistent and the fastest activation during 10 minutes of LDVF, suggesting it contains the source of VF wavefronts. There are no transmural APD gradients and no restitution relationship between APD and DI at any transmural layer, indicating these are not the primary factors in the mechanism of LDVF. [ABSTRACT FROM AUTHOR]

Intramural Optical Recordings. Introduction: Optical mapping of transmembrane potential (Vm) is an important tool in the investigation of impulse propagation in the heart. It provides valuable information about spatiotemporal changes of Vm that cannot be obtained by other techniques, but it presently is limited to measurements from the heart surfaces. Therefore, the goal of this work was to develop a technique for intramural multisite optical measurements of Vm using fiberoptic technology. Methods and Results: An optrode, a bundle of thin optical fibers, was developed for measuring intramural optical signals at multiple sites in the heart. The optrode consisted of seven fibers with diameter of 225 [mu]m arranged in a hexagonal pattern that were used to deliver excitation light to the myocardium, to collect the emitted fluorescence, and to project the light onto a 16 x 16 array of photodiode detectors. Rabbit hearts were stained with the Vm-sensitive dye RH-237. Fluorescence was excited using a 100-W Hg lamp. Intramural action potentials were recorded at multiple sites separated by 2 mm inside the left ventricle. Signal-to-noise (RMS) ratio was 21.2 ± 12 (n = 7) without averaging or ratiometry and with negligible cross-talk (<1.9%) between the neighboring photodiodes. The size of the recording area for an individual fiber was estimated at approximately 0.8 mm. Conclusion: These data demonstrate feasibility of multisite transmural measurements of Vm without signal averaging and ratiometry. This technique might become useful in studies of transmural impulse conduction during arrhythmias and defibrillation. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1196-1202, November 2003) [ABSTRACT FROM AUTHOR]

An electrical stimulus must create an electric field of approximately 1 V/cm in the extracellular space to stimulate myocardium during diastole. To initiate fibrillation by premature stimulation during the vulnerable period or to defibrillate, an extracellular electric field of approximately 6 V/cm is required, a value approximately six times greater than that necessary for diastolic pacing. Yet, the current strength of the pulse given to the stimulating electrode to initiate fibrillation or to defibrillate is much greater than six times the diastolic pacing threshold. The ventricular fibrillation threshold is typically 40 times greater than the diastolic pacing threshold expressed in terms of current. The defibrillation threshold in terms of current is typically thousands of times greater than the diastolic pacing threshold. The reason that these thresholds vary so much more in terms of stimulus current than in terms of extracellular potential gradient is that each of the three thresholds requires creation of the required potential gradient at different distances from the stimulating electrode. Pacing requires a potential gradient of approximately 1 V/cm only in a small liminal volume of tissue immediately adjacent to the electrode. Initiation of ventricular fibrillation by premature stimulation during the vulnerable period requires a potential gradient of approximately 6 V/cm about 1 cm away from the stimulating electrode to allow sufficient space for the central common pathway of a figure-eight reentrant circuit to form. Since the potential gradient falls off rapidly with distance from the stimulating electrode, a stimulating current about 40 times greater than the diastolic pacing threshold is required to generate an electric field of 6 V/cm approximately 1 cm away from the stimulating electrode. Defibrillation requires an electric field of approximately 6 V/cm throughout all or almost all of the ventricular myocardium. Since some portions of the ventricles can be more than 10 cm away from the defibrillation electrodes, a shock of several amps is required to create this field, a current thousands of times greater than the pacing threshold. [ABSTRACT FROM AUTHOR]

The effects of high voltage defibrillation shocks given to six swine were studied to determine if there is a limit to the advantage gained from increasing the shock strength. An endocardial electrode was placed in the right ventricle, and a 114-cm² cutaneous patch was placed on the left lateral thorax. Monophasic (10 msec) and single capacitor biphosic (5/5 msec) shocks with leading edge voltages of 200, 400, 600, 800, and 990 volts (approximately 2.3-59 J) were tested. For monophasic shocks, the probability of successful defibrillation ranged from 0% at 200 V to 90% at 990 V. The incidence of postshock arrhythmia increased from 0% for successful shocks at 600 V to 67% for successful shocks at 990 V. For biphasic shocks, the probability of success peaked at 97% for the 600-, 800-, and 990-V shocks. The incidence of postshock arrhythmia increased from 8% at 400 V to 55% at 990 V. Although more postshock arrhythmias occurred at lower strengths for biphasic than for monophasic shocks, an efficacy criterion, quantifying the probability of defibrillation success acid the probability that a postshock arrhythmia will not occur, was always higher for biphasic shocks. The probability of success never reached 100% for either waveform while the incidence of postshock arrhythmia increased as the shock strength increased. In conclusion, for the catheter-patch electrode configuration, increasing the shock strength does not always improve the probability of success and may increase the incidence of postshock arrhythmia. [ABSTRACT FROM AUTHOR]

Introduction: Sotalol and verapamil alone reduce reentry incidence during ventricular fibrillation (VF). We tested whether the combination of these two drugs had a synergistic effect on initiation, maintenance, and termination of VF., Methods: Six open-chest pigs received intravenous sotalol (1.5 mg/kg) followed by verapamil (0.136 mg/kg). VF threshold (VFT) was determined by a burst pacing protocol. Two 20 seconds episodes of VF were recorded from a 21 × 24 unipolar electrode plaque on the lateral posterior left ventricular epicardium before and after each drug. VF activation patterns were quantified. The duration of long duration VF (LDVF) maintenance was compared to our previously published data., Results: Sotalol alone and combined with verapamil significantly increased the VFT from 12.3 ± 4.1 to 20.3 ± 7.1 and 26.7 ± 8.6 mA compared with baseline (P < .05). Sotalol decreased the number of wavefronts by 20%, VF activation rate by 17% and conduction velocity 11%, while the addition of verapamil neutralized these effects. Addition of verapamil to sotalol further decreased the fractionation incidence from 14% to 29% and multiplicity from 24% to 31% compared with baseline. The combination of the two drugs increased the VF cycle length, decreased synchronicity, increased regularity index and shortened the duration of LDVF maintenance compared with our previous data of verapamil alone or no drug. Synchronicity index was lower and regularity index was higher in animals in which VF spontaneously terminated earlier than 10 minutes than in animals in which VF terminated longer than 10 minutes., Conclusion: The combination of sotalol and verapamil increased VFT but accelerated LDVF termination., (© 2018 John Wiley & Sons Ltd.)

Background: Understanding the mechanisms that drive ventricular fibrillation is essential for developing improved defibrillation techniques to terminate ventricular fibrillation (VF). Distinct organization patterns of chaotic, regular, and synchronized activity were previously demonstrated in VF that persisted over 1 to 2 minutes (long-duration VF [LDVF]). We hypothesized that activity on the endocardium may be driving these activation patterns in LDVF and that unsuccessful defibrillation shocks may alter activation patterns., Methods and Results: The study was performed using a 64-electrode basket catheter on the left ventricle endocardium and 54 6-electrode plunge needles inserted into the left ventricles of 6 dogs. VF was induced electrically, and after short-duration VF (10 seconds) and LDVF (7 minutes), shocks of increasing strengths were delivered every 10 seconds until VF was terminated. Endocardial activation patterns were classified as chaotic (varying cycle lengths and nonsynchronous activations), regular (highly repeatable cycle lengths), and synchronized (activation that spreads rapidly over the endocardium with diastolic periods between activations)., Conclusions: The results showed that the chaotic pattern was predominant in early VF, but the regular pattern emerges as VF progressed. The synchronized pattern only emerged occasionally during late VF. Failed defibrillation shocks changed chaotic and regular activation patterns to synchronized patterns in LDVF but not in short-duration VF. The regular and synchronized patterns of activation were driven by rapid activations on the endocardial surface that blocked and broke up transmurally, leading to an endocardial to epicardial activation rate gradient as LDVF progressed., (© 2017 American Heart Association, Inc.)

Objectives: This study sought to determine the characteristics of human LDVF, particularly as it contrasts with short-duration VF (SDVF), and evaluate the role of Purkinje fibers in its maintenance., Background: The electrophysiological mechanisms of long-duration ventricular fibrillation (LDVF) have not been studied in the human heart., Methods: VF was induced in 12 human Langendorff hearts, and the hearts were examined from initiation to LDVF (10 min). Endocardial, epicardial, and transmural plunge needle mapping were performed on the hearts. Simulated LDVF was studied in canine hearts to determine the potential role of Purkinje fiber automaticity., Results: The mean age at transplant was 48 ± 20 years, and the mean ejection fraction was <20%. The mean cycle length of local activation times on the endocardium was 252 ± 66 ms in SDVF and 441 ± 80 ms in LDVF (p = 0.0002). On the endocardium and the epicardium in LDVF, cycle length was 441 ± 80 ms and 590 ± 88 ms, respectively (p = 0.0002). No endocardial to epicardial activation frequency gradient was seen in SDVF. Simultaneous transmural needle activation was most common in SDVF, whereas endocardial to epicardial activation was most common in LDVF (47.7% and 38.8% of activations, respectively [p = 0.031]). Re-entry was less common in LDVF, and over time, wave break (i.e., nontransmural propagation of wave fronts) developed. Isochronal maps of the left ventricular endocardium in LDVF identified Purkinje potentials as preceding and predominating endocardial activations. In explanted canine heart preparations, rapid pacing led to spontaneous Purkinje fiber activity that was dependent on pacing rate and duration., Conclusions: LDVF in human hearts is characterized by focal endocardial activity with mid-myocardial wave break and not by re-entry. This arrhythmia is modulated by rapid activations in early VF that lead to spontaneous Purkinje fiber activity., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Legislation and sentiment have pushed large-animal electrophysiological research from the canine to the swine model. Anecdotal experience suggests that the swine is particularly sensitive to ventricular fibrillation (VF) induction, and radiofrequency ablation studies are consistent with this. Currently, no data exist directly comparing the VF threshold (VFT) in humans to swine. Because of the perceived difference in vulnerability to VF induction, we hypothesized that the VFT would be lower in swine compared to humans., Methods: Six anesthetized open-chested swine, 31 ± 2 kg, were studied that were part of an ongoing study with up to 6 h of previous closed-chest percutaneous pacing with repeated VF cycles. Similar to the human study of Horowitz et al., 24 pulses of 4 ms each were applied at a rate of 100 Hz during the ST segment to the epicardium via a pair of 7-mm diameter platinum electrodes whose centers were 15 mm apart. Current was increased until VF was induced., Results: The swine right ventricle (RV) VFT was 9.7 ± 2.1 mA [median = 9.0, interquartile range (IQR) = 7.8-12.0], and the left ventricle (LV) VFT was 10.7 ± 2.2 mA [median = 10.5, IQR = 8.8-12.5] (p = NS). Horowitz reported the RV VFT in six patients as 24.3 ± 5.2 mA [median = 24.5, IQR = 19.0-29.3] and the LV VFT in ten patients as 33.6 ± 9.5 mA [median = 36.5, IQR = 27.3-42.3] (p = .11). Both the RV and LV VFTs were lower for swine (p < 0.003), and each of the mean and median VFTs for the ventricles together was one third that of the humans., Conclusions: Swine are about three times as sensitive to the electrical induction of VF as are humans.

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., (Copyright © 2014 the American Physiological Society.)

Background: The mechanisms that maintain long duration ventricular fibrillation (LDVF) are unclear. The difference in distribution of the Purkinje system in dogs and pigs was explored to determine if Purkinje activation propagates to stimulate working myocardium (WM) during LDVF and WM pacing., Methods and Results: In-vivo extracellular recordings were made from 1044 intramural plunge and epicardial plaque electrodes in 6 pig and 6 dog hearts. Sinus activation propagated sequentially from the endocardium to the epicardium in dogs but not pigs. During epicardial pacing, activation propagated along the endocardium and traversed the LV wall almost parallel to the epicardium in dogs, but in pigs propagated away from the pacing site approximately perpendicular to the epicardium. After 1 minute of VF, activation rate near the endocardium was significantly faster than near the epicardium in dogs (P<0.01) but not pigs (P>0.05). From 2 to 10 minutes of LDVF, recordings exhibiting Purkinje activations were near the endocardium in dogs (P<0.01) but were scattered transmurally in pigs, and the WM activation rate in recordings in which Purkinje activations were present was significantly faster than the WM activation rate in recordings in which Purkinje activations were absent (P<0.01). In 10 isolated perfused dog hearts, the LV endocardium was exposed and 2 microelectrodes were inserted into Purkinje and adjacent myocardial cells. After 5 minutes of LDVF, mean Purkinje activation rate was significantly faster than mean WM activation rate (P<0.01)., Conclusion: These extracellular and intracellular findings about activation support the hypothesis that Purkinje activation propagates to stimulate WM during sinus rhythm, pacing, and LDVF.

Background: Previous studies showed that endocardial activation during long-duration ventricular fibrillation (VF) exhibits organized activity. We identified and quantified the different types of organized activity., Methods and Results: Two 64-electrode basket catheters were inserted, respectively, into the left ventricle and right ventricle of dogs to record endocardial activation from the endocardium during 7 minutes of VF (controls, n=6). The study was repeated with the K(ATP) channel opener pinacidil (n=6) and the calcium channel blocker flunarizine (n=6). After 2 minutes of VF without drugs, 2 highly organized left ventricular endocardial activation patterns were observed: (1) ventricular electric synchrony pattern, in which endocardial activation arose focally and either had a propagation sequence similar to sinus rhythm or arose near papillary muscles, and (2) stable pattern, in which activation was regular and repeatable, sometimes forming a stable re-entrant circuit around the left ventricular apex. Between 3 and 7 minutes of VF, the percent of time ventricular electric synchrony was present was control=25%, flunarizine=24% (P=0.44), and pinacidil=0.1% (P<0.001) and the percent of time stable pattern was present was control=71%, flunarizine=48% (P<0.001), and pinacidil=56% (P<0.001). The remainder of the time, nonstable re-entrant activation with little repeatability was present., Conclusions: After 3 minutes, VF exhibits 2 highly organized endocardial activation patterns 96% of the time, one potentially arising focally in the Purkinje system that was prevented with a K(ATP) channel opener but not a calcium channel blocker and the other potentially arising from a stable re-entrant circuit near the apical left ventricular endocardium.

Background: A subcutaneous implantable cardioverter defibrillator (S-ICD) could ease placement and reduce complications of transvenous ICDs, but requires more energy than transvenous ICDs. Therefore we assessed cardiac and chest wall damage caused by the maximum energy shocks delivered by both types of clinical devices., Methods: During sinus rhythm, anesthetized pigs (38 ± 6 kg) received an S-ICD (n = 4) and five 80-Joule (J) shocks, or a transvenous ICD (control, n = 4) and five 35-J shocks. An inactive S-ICD electrode was implanted into the same control pigs to study implant trauma. All animals survived 24 hours. Troponin I and creatine kinase muscle isoenzyme (CK-MM) were measured as indicators of myocardial and skeletal muscle injury. Histopathological injury of heart, lungs, and chest wall was assessed using semiquantitative scoring., Results: Troponin I was significantly elevated at 4 hours and 24 hours (22.6 ± 16.3 ng/mL and 3.1 ± 1.3 ng/mL; baseline 0.07 ± 0.09 ng/mL) in control pigs but not in S-ICD pigs (0.12 ± 0.11 ng/mL and 0.13 ± 0.13 ng/mL; baseline 0.06 ± 0.03 ng/mL). CK-MM was significantly elevated in S-ICD pigs after shocks (6,544 ± 1,496 U/L and 9,705 ± 6,240 U/L; baseline 704 ± 398 U/L) but not in controls. Electrocardiogram changes occurred postshock in controls but not in S-ICD pigs. The myocardium and lungs were histologically normal in both groups. Subcutaneous injury was greater in S-ICD compared to controls., Conclusion: Although CK-MM suggested more skeletal muscle injury in S-ICD pigs, significant cardiac, lung, and chest wall histopathological changes were not detected in either group. Troponin I data indicate significantly less cardiac injury from 80-J S-ICD shocks than 35-J transvenous shocks., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

We tested the hypothesis that after 2 minutes of ventricular fibrillation (VF), periods of highly organized activations occur on the endocardium, arising from an intramural mother rotor or triggered activity originating in the Purkinje fibers. In 6 anesthetized dogs, we recorded electrically induced VF from two-thirds of the endocardium with a 64-electrode basket catheter. In another 12 dogs, the study was repeated with the addition of the early afterdepolarization blocker pinacidil in 6 animals and the delayed afterdepolarization blocker flunarizine in the other 6 animals. We found that, in addition to periods of disorganized chaotic activation (type I pattern), at between 3 and 7 minutes of VF, 2 highly organized patterns were observed (type II pattern, regular activity and type III pattern, triggered activity). When present, these patterns were observed in all 64 electrodes simultaneously. Type II arises from the apex and may be an intramural mother rotor and type III arises focally in Purkinje fibers and may be caused by early afterdepolarizations. The optimal defibrillation strategy may be different for the 3 different VF patterns. Therefore, it is important to determine if these 3 patterns can be differentiated from the body surface electrocardiogram., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: We tested the hypothesis that the shape of the shock waveform affects not only the defibrillation threshold but also the amount of cardiac damage., Methods and Results: Defibrillation thresholds were determined for 11 waveforms-3 ascending-ramp waveforms, 3 descending-ramp waveforms, 3 rectilinear first-phase biphasic waveforms, a Gurvich waveform, and a truncated exponential biphasic waveform-in 6 pigs with electrodes in the right ventricular apex and superior vena cava. The ascending, descending, and rectilinear waveforms had 4-, 8-, and 16-millisecond first phases and a 3.5-millisecond rectilinear second phase that was half the voltage of the first phase. The exponential biphasic waveform had a 60% first-phase and a 50% second-phase tilt. In a second study, we attempted to defibrillate after 10 seconds of ventricular fibrillation with a single ≈30-J shock (6 pigs successfully defibrillated with 8-millisecond ascending, 8-millisecond rectilinear, and truncated exponential biphasic waveforms). Troponin I blood levels were determined before and 2 to 10 hours after the shock. The lowest-energy defibrillation threshold was for the 8-milliseconds ascending ramp (14.6±7.3 J [mean±SD]), which was significantly less than for the truncated exponential (19.6±6.3 J). Six hours after shock, troponin I was significantly less for the ascending-ramp waveform (0.80±0.54 ng/mL) than for the truncated exponential (1.92±0.47 ng/mL) or the rectilinear waveform (1.17±0.45 ng/mL)., Conclusions: The ascending ramp has a significantly lower defibrillation threshold and at ≈30 J causes 58% less troponin I release than the truncated exponential biphasic shock. Therefore, the shock waveform affects both the defibrillation threshold and the amount of cardiac damage.

Intramural gradients of intracellular Ca(2+) (Ca(i)(2+)) Ca(i)(2+) handling, Ca(i)(2+) oscillations, and Ca(i)(2+) transient (CaT) alternans may be important in long-duration ventricular fibrillation (LDVF). However, previous studies of Ca(i)(2+) handling have been limited to recordings from the heart surface during short-duration ventricular fibrillation. To examine whether abnormalities of intramural Ca(i)(2+) handling contribute to LDVF, we measured membrane voltage (V(m)) and Ca(i)(2+) 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, V(m) and Ca(i)(2+) 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 V(m) upstrokes during pacing and LDVF. In conclusion, the fact that V(m) upstrokes always preceded CaTs indicates that spontaneous Ca(i)(2+) oscillations in the working myocardium were not likely the reason for LDVF maintenance. Strong V(m)-Ca(i)(2+) desynchronization and the occurrence of long CaTs during LDVF indicate severely impaired Ca(i)(2+) handling and may potentially contribute to LDVF maintenance.

External mechanical forces can cause ventricular capture and fibrillation (i.e., commotio cordis). In animals, we showed that chest compressions (CCs) can also cause the phenomenon. The aim of the present study was to determine whether ventricular capture by CCs occurs in humans. Electronic rhythm strips were analyzed in 31 cases of out-of-hospital cardiac arrest. The timing of the CCs was identified from the changes in thoracic impedance between the defibrillator pads. Ventricular capture was defined as QRS complexes of similar morphology occurring intermittently but synchronized with the CC artifact and impedance waveform. Only intermittent ventricular capture was identified to avoid misclassifying constant motion artifacts or intrinsic rhythm as ventricular capture. Of the 29 patients who received CCs for ≥1 minute, minimal or stable motion artifact was present in 24. Intermittent ventricular capture was found in 7 of the 24 patients. In the patients with ventricular capture, the number of ventricular activations (from ventricular capture and native beats) was greater during the CCs than when the CCs was not being performed (18 ± 8.9 vs 9.7 ± 4.0 activations in 15 seconds, p = 0.01). However, in patients without ventricular capture, they were similar (6.8 ± 8.2 vs 7.2 ± 8.8 activations in 15 seconds, p = 0.47). Refibrillation occurred in 22 patients; it began during the CCs in 16 and closely following their initiation in 3. In conclusion, CCs during cardiopulmonary resuscitation can electrically stimulate the heart. Additional studies evaluating the effect of ventricular capture on cardiopulmonary resuscitation outcomes, its relation to refibrillation, and methods to prevent or time ventricular capture by CCs are warranted., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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.

The first recorded heart rhythm for cardiac arrest patients can either be ventricular fibrillation (VF) which is treatable with a defibrillator, or asystole or pulseless electrical activity (PEA) which are not. The time course for the deterioration of VF to either asystole or PEA is not well understood. Knowing the time course of this deterioration may allow for improvements in emergency service delivery. In addition, this may improve the diagnosis of possible electrocutions from various electrical sources including utility power, electric fences, or electronic control devices (ECDs) such as a TASER(®) ECD. We induced VF in 6 ventilated swine by electrically maintaining rapid cardiac capture, with resulting hypotension, for 90 seconds. No circulatory assistance was provided. They were then monitored for 40 minutes via an electrode in the right ventricle. Only 2 swine remained in VF; 3 progressed to asystole; 1 progressed to PEA. These results were used in a logistic regression model. The results are then compared to published animal and human data. The median time for the deterioration of electrically induced VF in the swine was 35 minutes. At 24 minutes VF was still maintained in all of the animals. We conclude that electrically induced VF is long-lived--even in the absence of chest compressions.

Background: A percutaneously placed, totally intravascular defibrillator has been developed that shocks via a right ventricular (RV) single-coil and titanium electrodes in the superior vena cava (SVC) and the inferior vena cava (IVC). This study evaluated the defibrillation threshold (DFT) with this electrode configuration to determine the effect of different biphasic waveform tilts and second-phase durations as well as the contribution of the IVC electrode., Methods: Eight Bluetick hounds (wt = 30-40 kg) were anesthetized and the RV coil (first-phase anode) was placed in the RV apex. The intravascular defibrillator (PICD®, Model no. IIDM-G, InnerPulse Inc., Research Triangle Park, NC, USA) was positioned such that the titanium electrodes were in the SVC and IVC . Ventricular fibrillation was electrically induced and a Bayesian up-down technique was employed to determine DFT with two configurations: RV to SVC + IVC and RV to SVC. Three waveform tilts (65%, 50%, and 42%) and two second-phase durations (equal to the first phase [balanced] and truncated at 3 ms [unbalanced]) were randomly tested. The source capacitance of the defibrillator was 120 μF for all waveforms., Results: DFT with the IVC electrode was significantly lower than without the IVC electrode for all waveforms tested (527 ± 9.3 V [standard error], 14.5 J vs 591 ± 7.4 V, 18.5 J, P < 0.001). Neither waveform tilt nor second-phase duration significantly changed the DFT., Conclusion: In canines, a totally intravascular implantable defibrillator with electrodes in the RV apex, SVC, and IVC had a DFT similar to that of standard nonthoracotomy lead systems. No significant effect was noted with changes in tilt or with balanced or unbalanced waveforms., (©2010, The Authors. Journal compilation ©2010 Wiley Periodicals, Inc.)

Vernakalant is a novel antiarrhythmic agent that has demonstrated clinical efficacy for the treatment of atrial fibrillation. Vernakalant blocks, to various degrees, cardiac sodium and potassium channels with a pattern that suggests atrial selectivity. We hypothesized, therefore, that vernakalant would affect atrial more than ventricular effective refractory period (ERP) and have little or no effect on ventricular defibrillation threshold (DFT). Atrial and ventricular ERP and ventricular DFT were determined before and after treatment with vernakalant or vehicle in 23 anesthetized male mixed-breed pigs. Vernakalant was infused at a rate designed to achieve stable plasma levels similar to those in human clinical trials. Atrial and ventricular ERP were determined by endocardial extrastimuli delivered to the right atria or right ventricle. Defibrillation was achieved using external biphasic shocks delivered through adhesive defibrillation patches placed on the thorax after 10 seconds of electrically induced ventricular fibrillation. The DFT was estimated using the Dixon "up-and-down" method. Vernakalant significantly increased atrial ERP compared with vehicle controls (34 ± 8 versus 9 ± 7 msec, respectively) without significantly affecting ventricular ERP or DFT. This is consistent with atrial selective actions and supports the conclusion that vernakalant does not alter the efficacy of electrical defibrillation.

Background: An intravascular, percutaneously placed implantable defibrillator (InnerPulse percutaneous intravascular cardioverter-defibrillator [PICD]) with a right ventricular (RV) single-coil lead and titanium electrodes in the superior vena cava (SVC) and the inferior vena cava (IVC) has been developed., Objective: The purpose of this study was to compare defibrillation thresholds (DFTs) of the PICD to those of a conventional implantable cardioverter-defibrillator (ICD) in canines., Methods: Eight Bluetick hounds were randomized to initial placement of either a PICD or a conventional ICD. For PICD DFTs, a single-coil RV defibrillator lead was placed in the RV apex, and the device was positioned in the venous vasculature with electrodes in the SVC and IVC. With the conventional ICD, an RV lead was placed in the RV apex and an SVC coil was appropriately positioned. The ICD active can (AC) was implanted in a subcutaneous pocket formed in the left anterior chest wall and connected to the lead system. DFT was determined by a three-reversal, step up-down method to estimate the 80% success level. Two configurations were tested for the conventional ICD (#1: RV to SVC+AC; #2: RV to AC). A single configuration (RV to SVC+IVC) was evaluated for the PICD., Results: Mean PICD DFT was 14.8 ± 1.53 (SE) J. Conventional #1 configuration demonstrated mean DFT of 20.2 ± 2.45 J and #2 of 27.5 ± 1.95 J. The PICD had a significantly lower DFT than the better conventional ICD configuration (#1; mean difference 5.4 ± 2.1 J, P <.05, paired t-test, N = 8)., Conclusion: The new intravascular defibrillator had a significantly lower DFT than the conventional ICD in this canine model., (Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The risk of VF (ventricular fibrillation) from continuous AC utility (50/60 Hz) power has been well quantified and is reflected in accepted standards. Similarly, the required charge for a single pulse delivered during the T-wave of the ECG is also quantified. However, there are no studies that deal with the VF risk of a train of multiple short pulses such as those used in electric fences and conducted electrical weapons (CEWs). We studied 5 swine with an electrode placed through the anterior chest such that the tip was 10 mm from the epicardium. A return electrode was attached remotely to the lower abdomen. Five-second trains of 100 μs pulses at rates of 10-70 PPS (pulses per second) were delivered with gradually increasing charges until VF was induced. The VF threshold was also determined for 60 Hz AC current. As expected, the VF charge threshold decreased with increasing rates. For pulse rates between 10-30 PPS, the aggregate current (= charge • pulse rate) was constant at the VF threshold. The VF threshold in terms of AC RMS current was 7.4 ± 1.9 times the aggregate current VF threshold for the rapid short pulses. These results may have utility for setting safety standards for electric fences and for CEWs such as TASER® CEWs. This also allows for the risk assessment of CEWs by comparison to international electrical safety standards. The output of these weapons appears to be well below the VF risk limits as set by these standards.

Unlabelled: Periods of Highly Organized Activation During VF., Background: Little is known about long-duration ventricular fibrillation (LDVF), lasting 1-10 minutes when resuscitation is still possible., Methods and Results: To determine global left ventricle (LV) endocardial activation during LDVF, 6 canines (9.5 ± 0.8 kg) received a 64-electrode basket catheter in the LV, a right ventricular (RV) catheter, and a 12-lead electrocardiogram (ECG). Activation sequences of 15 successive cycles after initiation and after 1, 2, 3, 5, 7, and 10 minutes of LDVF were determined. Early during VF, LV endocardial activation was complex and present throughout most (78.0 ± 9.7%) of each cycle consistent with reentry. After 3-7 minutes of LDVF in 5 animals, endocardial activation became highly synchronized and present for only a small percentage of each cycle (18.2 ± 7.7%), indicating that LV endocardial reentry was no longer present. During this synchronization, activations arose focally in Purkinje fibers and spread as large wavefronts to excite the Purkinje system followed by the subendocardial working myocardium. During this synchronization, the ECG continued to appear irregular, consistent with VF, and LV cycle length (183 ± 29 ms) was significantly different than RV cycle length (144 ± 14 ms) and significantly different than the LV cycle length when synchronization was not present (130 ± 11 ms)., Conclusion: After 3-7 minutes of LDVF, a highly organized, synchronous, focal LV endocardial activation pattern frequently occurs that is not consistent with reentry but is consistent with triggered activity or abnormal automaticity in Purkinje fibers. The ECG continues to appear irregular during this period, partially because of differences in LV and RV cycle lengths., (© 2010 Wiley Periodicals, Inc.)

Electrical shock has been the one effective treatment for ventricular fibrillation for several decades. With the advancement of electrical and optical mapping techniques, histology, and computer modeling, the mechanisms responsible for defibrillation are now coming to light. In this review, we discuss recent work that demonstrates the various mechanisms responsible for defibrillation. On the cellular level, membrane depolarization and electroporation affect defibrillation outcome. Cell bundles and collagenous septae are secondary sources and cause virtual electrodes at sites far from shocking electrodes. On the whole-heart level, shock field gradient and critical points determine whether a shock is successful or whether reentry causes initiation and continuation of fibrillation.

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 x 9 x 6, 2-mm spacing) that allowed us to map intramural activation sequences. At 2.5 + or - 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 + or - 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.

Introduction: Since the initial development of the defibrillator, there has been concern that, while delivery of a large electric shock would stop fibrillation, it would also cause damage to the heart. This concern has been raised again with the development of the biphasic defibrillator., Objective: To compare defibrillation efficacy, postshock cardiac function, and troponin I levels following 150-J and 360-J shocks., Methods: Nineteen swine were anesthetized with isoflurane and instrumented with pressure catheters in the left ventricle, aorta, and right atrium. The animals were fibrillated for 6 minutes, followed by defibrillation with either low-energy (n = 8) or high-energy (n = 11) shocks. After defibrillation, chest compressions were initiated and continued until return of spontaneous circulation (ROSC). Epinephrine, 0.01 mg/kg every 3 minutes, was given for arterial blood pressure < 50 mmHg. Hemodynamic parameters were recorded for four hours. Transthoracic echocardiography was performed and troponin I levels were measured at baseline and four hours following ventricular fibrillation (VF)., Results: Survival rates at four hours were not different between the two groups (low-energy, 5 of 8; high-energy, 7 of 11). Results for arterial blood pressure, positive dP/dt (first derivative of pressure measured over time, a measure of left ventricular contractility), and negative dP/dt at the time of lowest arterial blood pressure (ABP) following ROSC were not different between the two groups (p = not significant [NS]), but were lower than at baseline. All hemodynamic measures returned to baseline by four hours. Ejection fractions, stroke volumes, and cardiac outputs were not different between the two groups at four hours. Troponin I levels at four hours were not different between the two groups (12 +/- 11 ng/mL versus 21 +/- 26 ng/mL, p = NS) but were higher at four hours than at baseline (19 +/- 19 ng/mL versus 0.8 +/- 0.5 ng/mL, p < 0.05, groups combined)., Conclusion: Biphasic 360-J shocks do not cause more cardiac damage than biphasic 150-J shocks in this animal model of prolonged VF and resuscitation.

Background: Pauses during chest compressions are thought to have a detrimental effect on resuscitation outcome. The Guidelines 2005 have recently eliminated the post-defibrillation pause. Previous animal studies have shown that multiple pauses of increasing duration decrease resuscitation success. We investigated the effect of varying the characteristics of a single pause near defibrillation on resuscitation outcome., Methods: Part A: 48 swine were anesthetized, fibrillated for 7min and randomized. Chest compressions were initiated for 90s followed by defibrillation and then resumption of chest compressions. Four groups were studied-G2000: 40s pause beginning 20s before, and ending 20s after defibrillation, A1: a 20s pause just before defibrillation, A2: a 20s pause ending 30s prior to defibrillation, and group A3: a 10s pause ending 30s prior to defibrillation. Part B: 12 swine (Group B) were studied with a protocol identical to Part A but with no pause in chest compressions. Primary endpoint was survival to 4h., Results: The survival rate was significantly higher for groups A1, A2, A3, and B (5/12, 7/12, 5/12, and 5/12 survived) than for the G2000 group (0/12, p<0.05). Survival did not differ significantly among groups A1, A2, A3, and B., Conclusions: These results suggest that the Guidelines 2005 recommendation to omit the post-shock pulse check and immediately resume chest compressions may be an important resuscitation protocol change. However, these results also suggest that clinical maneuvers further altering a single pre-shock chest compression pause provide no additional benefit.

Background: Cycle length (CL) increases as ventricular fibrillation (VF) progresses., Objective: The purpose of this study was to test the hypotheses that increased CL is due to increased diastolic interval (DI), not increased action potential duration (APD), and that the DI increase is not solely due to increased postrepolarization refractoriness., Methods: In 10 swine, VF was recorded for 20 minutes using a floating microelectrode through a hole in a 504-electrode epicardial plaque. Mean APD, DI, action potential amplitude (APA), maximum change in voltage during the AP upstroke (V(max)), and CL were calculated from the floating microelectrode recordings each minute of VF. The refractory period was estimated from the minimum DI (DI(min)). In two animals, rapid pacing was performed to gauge refractoriness., Results: As VF progressed, CL, DI, and DI(min) increased (P <.05), whereas APD, V(max), and APA decreased (P <.05). At 20 minutes, DI(min) was not different from mean DI at VF onset. Pacing captured, but 53% of paced wavefronts blocked within the plaque., Conclusion: Increasing CL in VF is due to increased DI and not APD, which shortens. The increase in DI(min) over time is much less than the increase in mean DI, indicating that the myocardium is excitable during much of the DI. This finding, along with the ability to pace at a CL shorter than the native VF CL and the poor paced wavefront propagation, suggests that the increase in DI is due not only to increased postrepolarization refractoriness but also to poor wavefront propagation because of decreased APA and V(max) secondary to global ischemia caused by VF.

Ventricular fibrillation (VF), despite its declining incidence as a cause of sudden cardiac death, is still a major health problem. The underlying mechanisms for the maintenance of VF are still disputed. Studies suggest that VF is unlikely one static mechanism but rather a dynamic process of electrical derangement that changes with duration. The 2 principal proposed mechanisms of VF are multiple wavelets and mother rotors. Most studies of these proposed mechanisms for VF maintenance have been during the first minute of VF. However, the time to external defibrillation in the community and pre-hospital settings, where the majority of sudden cardiac death occurs, ranges from 4 to 10 min and the time to defibrillation seems crucial because the odds of survival worsen with delay. Recent studies during the first 10 min of VF suggest that Purkinje fibers are important in maintaining VF after the first 1 to 2 min, either as a part of a reentrant circuit or as a source of focal activations.

Background: Recent studies suggest that during ventricular fibrillation (VF) epicardial vessels may be a site of conduction block and the posterior papillary muscle (PPM) in the left ventricle (LV) may be the location of a "mother rotor." The goal of this study was to obtain evidence to support or refute these possibilities., Methods: Epicardial activation over the posterior LV and right ventricle (RV) was mapped during the first 20 s of electrically induced VF in six open-chest pigs with a 504 electrode plaque covering a 20 cm(2) area centered over the posterior descending artery (PDA)., Results: The locations of epicardial breakthrough as well as reentry clustered in time and space during VF. Spatially, reentry occurred significantly more frequently over the LV than the RV in all 48 episodes, and breakthrough clustered near the PPM (p < 0.001). Significant temporal clustering occurred in 79% of breakthrough episodes and 100% of reentry episodes. These temporal clusters occurred at different times so that there was significantly less breakthrough when reentry was present (p < 0.0001). Conduction block occurred significantly more frequently near the PDA than elsewhere., Conclusions: The PDA is a site of epicardial block which may contribute to VF maintenance. Epicardial breakthrough clusters near the PPM. Reentry also clusters in space but at a separate site. The fact that breakthrough and reentry cluster at different locations and at different times supports the possibility of a drifting filament at the PPM so that at times reentry is present on the surface but at other times the reentrant wavefront breaks through to the epicardium.

Background: Knowledge of the shock potential gradient (nablaV) and postshock activation is limited to internal defibrillation of short-duration ventricular fibrillation (SDVF)., Objective: The purpose of this study was to determine these variables after external defibrillation of long-duration VF (LDVF)., Methods: In six pigs, 115-20 plunge needles with three to six electrodes each were inserted to record throughout both ventricles. After the chest was closed, the biphasic defibrillation threshold (DFT) was determined after 20 seconds of SDVF with external defibrillation pads. After 7 minutes of LDVF, defibrillation shocks that were less than or equal to the SDVF DFT strength were given., Results: For DFT shocks (1632 +/- 429 V), the maximum minus minimum ventricular voltage (160 +/- 100 V) was 9.8% of the shock voltage. Maximum cardiac nablaV (28.7 +/- 17 V/cm) was 4.7 +/- 2.0 times the minimum nablaV (6.2 +/- 3.5 V/cm). Although LDVF did not increase the DFT in five of the six pigs, it significantly lengthened the time to earliest postshock activation following defibrillation (1.6 +/- 2.2 seconds for SDVF and 4.9 +/- 4.3 seconds for LDVF). After LDVF, 1.3 +/- 0.8 episodes of spontaneous refibrillation occurred per animal, but there was no refibrillation after SDVF., Conclusion: Compared with previous studies of internal defibrillation, during external defibrillation much less of the shock voltage appears across the heart and the shock field is much more even; however, the minimum nablaV is similar. Compared with external defibrillation of SDVF, the biphasic external DFT for LDVF is not increased; however, time to earliest postshock activation triples. Refibrillation is common after LDVF but not after SDVF in these normal hearts, indicating that LDVF by itself can cause refibrillation without requiring preexisting heart disease.

Background: Interest in combining antiarrhythmic drugs has been prompted by the lack of efficacy of monotherapies and the toxicity resulting from high doses of individual agents., Objectives: We tested the hypothesis that procainamide and sotalol combined have greater beneficial effects on restitution, on the dispersion of refractoriness, and on decreasing the complexity of ventricular fibrillation (VF) than either drug alone., Methods: Six open-chest pigs received intravenous procainamide (15 mg/kg load and 50 microg/kg/min maintenance) followed by sotalol (1.5 mg/kg). Another six pigs received sotalol first and procainamide second. Before drugs and after each drug, 20-second episodes of electrically induced VF were recorded from a 21 x 24 unipolar electrode plaque (2 mm spacing) sutured on the lateral posterior left ventricular epicardium. Restitution properties and dispersion of refractoriness were estimated from activation recovery intervals during pacing., Results: The combination of the two drugs reduced the maximum slope of the restitution curve and during VF reduced the number of wavefronts, the activation rate, the percentage of wavefront families exhibiting reentry, and the conduction velocity more than either drug alone. In addition, in the group that received sotalol first, both drugs together reduced the SD and the coefficient of variation of the spatial dispersion of refractoriness compared with baseline., Conclusions: Procainamide and sotalol combined have greater beneficial effects on restitution properties, dispersion of refractoriness, and the complexity of VF than either drug alone compared with baseline.

Background: During resuscitation, fibrillation often recurs. In swine, we studied refibrillation after long-duration ventricular fibrillation, investigating an association with chest compressions (CCs)., Methods and Results: In protocol A, 47 episodes of long-duration ventricular fibrillation lasting at least 2.5 minutes were induced in 8 animals. After defibrillation, CCs were required for 35 episodes and delivered with a pneumatic device (Lucas cardiopulmonary resuscitation). In 9 episodes, refibrillation occurred within 2 seconds of CC initiation (group 1) and in 26 episodes, CCs were delivered without refibrillation (group 2). From the ECG and intracardiac electrodes, the RR interval preceding CCs, the shortest cycle length during the first 2 CCs (short), and the preceding cycle length (long) were measured. A similar study was conducted in 3 more animals without intracardiac catheters (protocol B). In protocol A, the mean RR before CC was 665+/-292 ms in group 1 and 769+/-316 in group 2. CCs stimulated ventricular beats in all 35 episodes. The short and long intervals were shorter in group 1 (215+/-31 and 552+/-210 ms) than in group 2 (402+/-153 and 699+/-147 ms) (P=0.009 and P=0.04, respectively). The prematurity index (short/RR) was lower in group 1 than in group 2 (0.35+/-0.09 vs 0.58+/-0.21; P<0.01). A short interval <231 ms predicted refibrillation with 88% sensitivity and 91% specificity. In protocol B, CCs were required in 11 episodes, causing ventricular stimulation in all of them and ventricular fibrillation within the first 2 CCs in 3., Conclusions: Under some conditions, CC during resuscitation can stimulate the ventricles and initiate ventricular fibrillation by a long-short sequence.

Background: Acute ischemia causes myriad changes including increased catecholamines. We tested the hypothesis that elevated catecholamines alone are arrhythmogenic., Methods and Results: A 504 electrode sock was placed over both ventricles in six open-chest pigs. During control infusion of saline through a catheter in the left anterior descending coronary artery (LAD), no sustained arrhythmias occurred, and the refractory period estimated by the activation recovery interval (ARI) was 175 +/- 14 ms in the LAD bed below the catheter. After infusion of isoproterenol at 0.1 microg/kg/min through the catheter, the ARI in this bed was significantly reduced to 109 +/- 10 ms. A sharp gradient of refractoriness of 43 +/- 10 ms was at the border of the perfused bed. Sustained monomorphic ventricular tachycardia occurred after drug infusion in the perfused bed or near its boundary in all animals with a cycle length of 329 +/- 26 ms and a focal origin. The maximum slope of the ARI restitution curve at the focal origins of the tachyarrhythmias was always <1 (0.62 +/- 0.15). Similar results with a focal arrhythmia origin occurred in two additional pigs in which intramural mapping was performed with 36 plunge needle electrodes in the left ventricular perfused bed., Conclusion: Regional elevation of a catecholamine, which is one of the alterations produced by acute ischemia, can by itself cause tachyarrhythmias. These arrhythmias are closely associated with a shortened refractory period and a large gradient of the spatial distribution of refractoriness but not with a steep restitution curve.

Introduction: Sudden death is prevalent in heart failure patients. We tested an implantable ventricular support device consisting of a wireform harness with one or two pairs of integrated defibrillation electrode coils., Methods and Results: The device was implanted into six pigs (36-44 kg) through a subxiphoid incision. Peak voltage (V) defibrillation thresholds (DFT) were determined for five test configurations compared with a control transvenous lead (RV to CanPect). Defibrillator can location (abdominal or pectoral) and common coil separation on the implant (0 degrees or 60 degrees ) were studied.(.) The DFT for RV60 to LV60 + CanPect was significantly less than control (348 +/- 57 vs 473 +/- 27 V, P < 0.05). The DFTs for other vectors were similar to control except for RV0 to LV0 + CanAbd (608 +/- 159 V). The device was implanted into 12 adult dogs for 42, 90, or 180 days with DFT and pathological examination performed at the terminal study. Cardiac pressures were determined at baseline, after implantation, and at the terminal study. The DFT was also determined in a separate group of four dogs at 42 days following implantation of the support device with one pair of defibrillation electrodes. The DFTs at implant and explant in dogs with one pair (8 +/- 1.5 Joules [J] and 6 +/- 1.9 J) or two pairs (8 +/- 3.4 J and 7 +/- 1.9 J) of defibrillation electrodes were not significantly different from each other but significantly less than control measured at the terminal study (18 +/- 3.4 J). Left-sided pressures were significantly decreased at explant but within expected normal ranges. Right-sided pressures were not different except for RV systolic. Histopathology indicated mild to moderate epicardial inflammation and fibrosis, consistent with a foreign body healing response., Conclusions: This defibrillation-enabled ventricular support system maintained mechanical functionality for up to 6 months while inducing typical chronic healing responses. The DFT was equal to or lower than a standard transvenous vector.

Endocardial mapping has suggested that Purkinje fibers may play a role in the maintenance of long-duration ventricular fibrillation (LDVF). To determine the influence of Purkinje fibers on LDVF, we chemically ablated the Purkinje system with Lugol solution and recorded endocardial and transmural activation during LDVF. Dog hearts were isolated and perfused, and the ventricular endocardium was exposed and treated with Lugol solution (n = 6) or normal Tyrode solution as a control (n = 6). The left anterior papillary muscle endocardium was mapped with a 504-electrode (21 x 24) plaque with electrodes spaced 1 mm apart. Transmural activation was recorded with a six-electrode plunge needle on each side of the plaque. Ventricular fibrillation (VF) was induced, and perfusion was halted. LDVF spontaneously terminated sooner in Lugol-ablated hearts than in control hearts (4.9 +/- 1.5 vs. 9.2 +/- 3.2 min, P = 0.01). After termination of VF, both the control and Lugol hearts were typically excitable, but only short episodes of VF could be reinduced. Endocardial activation rates were similar during the first 2 min of LDVF for Lugol-ablated and control hearts but were significantly slower in Lugol hearts by 3 min. In control hearts, the endocardium activated more rapidly than the epicardium after 4 min of LDVF with wave fronts propagating most often from the endocardium to epicardium. No difference in transmural activation rate or wave front direction was observed in Lugol hearts. Ablation of the subendocardium hastens VF spontaneous termination and alters VF activation sequences, suggesting that Purkinje fibers are important in the maintenance of LDVF.