Effects of combination of sotalol and verapamil on initiation, maintenance, and termination of ventricular fibrillation in swine hearts.

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.

Endocardial Activation Drives Activation Patterns During Long-Duration Ventricular Fibrillation and Defibrillation.

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.

Ventricular fibrillation: are swine a sensitive species?

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.

Mechanisms of Long-Duration Ventricular Fibrillation in Human Hearts and Experimental Validation in Canine Purkinje Fibers.

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.

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.

The importance of Purkinje activation in long duration ventricular fibrillation.

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.

Long-duration ventricular fibrillation exhibits 2 distinct organized states.

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.

Evaluation of acute cardiac and chest wall damage after shocks with a subcutaneous implantable cardioverter defibrillator in Swine.

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.

Different types of long-duration ventricular fibrillation: can they be identified by electrocardiography.

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.

Ascending-ramp biphasic waveform has a lower defibrillation threshold and releases less troponin I than a truncated exponential biphasic waveform.

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 optical mapping of V(m) and Ca(i)2+ during long-duration ventricular fibrillation in canine hearts.

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.

Effect of chest compressions on ventricular activation.

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.

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

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 stability of electrically induced ventricular fibrillation.

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.

Intramural activation during early human ventricular fibrillation.

BACKGROUND: We investigated patterns of intramural activation in early human ventricular fibrillation (VF) and hypothesized that intramural reentry colocalizes to sites with increased intramural fibrosis. METHODS AND RESULTS: Thirteen human Langendorff hearts were used for this study. Twenty-five plunge needles (4 unipoles/needle) were used to map 100 intramural sites. For the global mapping component, 11 20-s episodes of early VF were studied in 6 hearts. Simultaneous activation of all 4 electrodes was the most common pattern observed in 48.7% of needles, followed by an endocardial-to-epicardial activation pattern (9.8% of needles) and epicardial-to-endocardial activation pattern (5.5% of needles); 19.3% of needles had nonuniform multidirectional patterns. In 2 orthogonal planes, 1 parallel and 1 perpendicular to the epicardium and endocardium, reentry was detected in 14.3% of beats at any 1 level, and 5.8% of these were transmural. Simultaneous mapping of the epicardium and endocardium in 5 hearts detected concurrently rotating rotors with similar chirality and cycle length, suggesting the presence of transmural scroll waves (n=6), which was confirmed by high-resolution fixed-space mapping in 2 of those hearts plus 1 additional heart. Transmural optical mapping in 1 additional heart confirmed simultaneous epicardial and endocardial activation. Histopathology revealed greater fibrosis at sites of reentry compared to areas without (53.3±11.9% versus 27.5±2.4%, P=0.02). CONCLUSIONS: Intramural activation patterns suggest that early human VF does not organize as multiple reentrant wavefronts but is best explained by transmural scroll wave activation. Intramural reentry localizes to regions of greater intramural fibrosis.

Vernakalant selectively prolongs atrial refractoriness with no effect on ventricular refractoriness or defibrillation threshold in pigs.

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.

Implantable intravascular defibrillator: evaluation of defibrillation waveforms with inferior vena cava electrode system.

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.

Novel intravascular defibrillator: defibrillation thresholds of intravascular cardioverter-defibrillator compared to conventional implantable cardioverter-defibrillator in a canine model.

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.