Delayed afterdepolarization inhibitor: a potential pharmacologic intervention to improve defibrillation efficacy

INTRODUCTION: Electrical and optical mapping studies of defibrillation have demonstrated that following shocks of strength near the defibrillation threshold (DFT), the first several postshock cycles always arise focally. No immediate postshock reentry was observed. Delayed afterdepolarizations (DADs) have been suggested as a possible cause of this rapid repetitive postshock activity. The aim of this study was to test the hypothesis that DFT is decreased by application of a DAD inhibitor. METHODS AND RESULTS: Six pigs (30-35 kg) were studied. First, control DFT was determined using a three-reversal up/down protocol. Each shock (RV-SVC, biphasic, 6/4 msec) was delivered after 10 seconds of ventricular fibrillation (VF). Then, flunarizine (a DAD inhibitor) was injected intravenously (2 mg/kg bolus and 4 mg/kg/hour maintenance) and the DFT was again determined. A third DFT was determined 50 minutes after drug infusion was terminated to allow the drug to wash out. DFT after flunarizine application (520 +/- 90 V, 14 +/- 3 J) was significantly lower than control DFT (663 +/- 133 V, 23 +/- 4 J). After the drug washed out, DFT (653 +/- 107 V, 22 +/- 4 J) returned to the control DFT value (P = 0.6). Flunarizine reduced the DFT approximately 22% by leading-edge voltage and approximately 40% by energy. CONCLUSION: Flunarizine, a DAD inhibitor, significantly improved defibrillation efficacy. This finding suggests that DADs could be the source of the rapid repetitive focal activation cycles arising after failed near-DFT shocks before degeneration back into VF. Future studies are needed to investigate the cause of the earliest postshock activation and to determine if the DADs are responsible.     

Three-dimensional mapping of earliest activation after near-threshold ventricular defibrillation shocks

INTRODUCTION: Following shocks with a 50% defibrillation success (DFT50) delivered from electrodes at the right ventricular (RV) apex and superior vena cava (SVC), the earliest epicardial postshock activation always appears focally in the left ventricular (LV) apex for both successful and failed shocks. Because the heart is a three-dimensional (3D) structure, questions remain whether this activation truly arises from a focus or the focal pattern represents epicardial breakthrough resulting from intramural reentry. To answer these questions, 3D electrical mapping was performed. METHODS AND RESULTS: In six pigs, 60 to 84 epoxy fiberglass needles (0.7-mm-diameter), each containing six electrodes 2 mm apart, were inserted into the LV with 3- to 5-mm spacing around the apex and 5- to 10-mm spacing near the base. Ten DFT50 shocks (RV-->SVC, biphasic, 6/4 msec) were delivered after 10 seconds of fibrillation in each animal. The first five activations after each shock were mapped. Of 60 DFT50 shocks, 31 were successful, of which the first postshock cycle was a sinus beat in 13. In the other 18 successful shock episodes, the first postshock activation was detected 63 +/- 16 msec after the shock, which was not significantly different from the 58 +/- 23 msec postshock interval for the 29 failed shock episodes. In these 47 successful and failed shock episodes, the earliest postshock activation always arose focally from the LV apex. Its origin was in the subepicardium in 76% +/- 17%, midmyocardium in 16% +/- 12%, and subendocardium in 8% +/- 6% of cases. CONCLUSION: Following near-DFT50 shocks, the first postshock cycles did not arise by macroreentry. Instead, they originated from a true focus or microreentry, most commonly near the epicardium.     

Prediction of defibrillation outcome by epicardial activation patterns following shocks near the defibrillation threshold

INTRODUCTION: Ventricular defibrillation is probabilistic and shock strength dependent. We investigated the relationship between defibrillation outcome and postshock activation patterns for shocks of the same strength (approximately 50% probability of success for defibrillation [ED50] to yield an equal number of successful and failed shocks). METHODS AND RESULTS: In five pigs, 10 shocks of approximately ED50 strength (right ventricle-superior vena cava, biphasic, 6/4 msec) were delivered after 10 seconds of ventricular fibrillation (VF). Epicardial activation sequences following shocks were mapped with a 504-electrode shock and analyzed by animating dV/dt of the electrograms. Intercycle interval (ICI, time between the onset of successive postshock cycles), wavefront conduction time (WCT, time between the earliest and latest activation of a cycle), and overlapping index (WCT of cycle[n]/ICI of cycle[n+1]) were determined for the first five postshock cycles. An overlapping index >1 indicates overlap between successive cycles. Of 50 defibrillation attempts, 25 were successes. There was no difference between successful and failed episodes for both ICI (68 +/- 9 msec vs 62 +/- 10 msec) and WCT (97 +/- 24 msec vs 100 +/- 14 msec) of cycle 1. However, starting at cycle 2, the ICI was longer, and the WCT was shorter for successful than failed episodes (P < 0.01). Overlapping cycles (index > 1) were found during the transition from cycles 2 through 5 in all failed (index >1) and in no successful episodes. CONCLUSIONS: (1) Defibrillation outcome cannot be determined during the first postshock cycle. (2) At least three rapid successive cycles with overlap of cycles 2 and 3 are present in all failed and in no successful episodes. (3) The overlapping index is a marker to predict defibrillation outcome.     

The effects of ventricular fibrillation duration and site of initiation on the defibrillation threshold during early ventricular fibrillation

Objectives. The purpose of this study was to determine if the defibrillation threshold (DFT) is lower during the first few cycles of ventricular fibrillation (VF) than after 10 s of VF and, if so, if the effect is caused by local or global factors.Background. The DFT may be low very early during VF because: (1) for the first few cycles VF arises from a localized region close to a defibrillation electrode where the shock field is strong (local factors), or (2) during early VF the effects of ischemia and sympathetic discharge have not yet fully developed and the heart has not yet completely dilated (global factors).Methods. Protocol 1 included seven pigs in which a defibrillation electrode and a pacing catheter were both placed in the right ventricular apex. VF was induced by delivering a high current premature stimulus from the pacing catheter that should have caused reentry confined to the right ventricular apex for the first few cycles of VF. A bipolar electrogram was recorded from the tip of the defibrillation catheter. Using a three reversal up–down protocol, the DFT was determined for biphasic shocks delivered after 1, 2, 3, 4, 5, 7, 10, 15, 20 and 25 activations in this electrogram and after 10 s (control). Protocol 2 included seven pigs undergoing the same procedure as in protocol 1 except that an additional pacing catheter was placed in the left ventricle. Defibrillation thresholds were determined after 1, 2, 3, 4 and 5 VF activations following VF induction from the right ventricle (RV) or the left ventricle (LV) and after 10 s (control).Results. In protocol 1, the mean ± SD DFTs were lower during the first three cycles than after 10 s of VF (3.0 ± 4.1 J for the first VF cycle vs 15.8 ± 6.6 J after 10 s of VF, p < 0.05). In protocol 2, the DFT for the first few cycles of VF induced away from the defibrillation electrode in the LV (6.9 ± 1.4 J for the first VF cycle) was significantly lower than that after 10 s of VF (16.0 ± 2.2 J), whereas the DFT for the first few cycles induced near the defibrillation electrode in the right ventricular apex was significantly lower (2.3 ± 2.7 J for the first VF cycle) than that induced from the LV.Conclusions. This study demonstrates that the DFT is significantly lower during the first few VF cycles of VF than after 10 s of VF and that this decrease may be caused by both local factors and global factors. These results provide an impetus for exploring earlier shock delivery in implantable devices.     

长时间心室颤动除颤成功后早期复发的电生理作用机制

目的通过整体左室心内膜电生理标测研究长时间心室颤动(简称室颤)除颤成功后室颤早期复发的电生理作用机制。方法将64极伞状电极经颈动脉逆行植入6只正常比格犬的左室行电生理标测。通过快速电刺激,分别诱发20 s短时间室颤和7 min长时间室颤,随后给予体内双相波除颤。比较不同时间室颤除颤成功后最早激动时间和室颤复发率。利用电生理激动图分析室颤复发时的激动特征。结果 6只动物累计短时间室颤除颤成功24次,无1次室颤复发。7 min长时间室颤除颤成功6次,每次成功除颤后至少1次室颤早期复发,观察时间内累计复发14次,平均每只动物发作2.3±1.9次,与短时间室颤相比,室颤复发率显著升高(P<0.01)。与短时间室颤相比,长时间室颤除颤后最早激动时间显著延长(5 125±3 373 ms vs 322±166 ms,P<0.01)。14次复发室颤前,均有室性早搏。电生理标测提示,10次复发源自间隔部附近的局灶活动。结论无器质性心脏疾病的长时间室颤除颤成功后室颤早期复发十分常见,但未见于短时间室颤,提示长时间室颤本身可致室颤复发,其复发的起始电生理机制可能与局灶兴奋相关。     

Reentry site during fibrillation induction in relation to defibrillation efficacy for different shock waveforms

INTRODUCTION: Unsuccessful defibrillation shocks may reinitiate fibrillation by causing postshock reentry. METHODS AND RESULTS: To better understand why some waveforms are more efficacious for defibrillation, reentry was induced in six dogs with 1-, 2-, 4-, 8-, and 16-msec monophasic and 1/1- (both phases 1 msec) 2/2-, 4/4-, and 8/8-msec biphasic shocks. Reentry was initiated by 141+/-15 V shocks delivered from a defibrillator with a 150-microF capacitance during the vulnerable period of paced rhythm (183+/-12 msec after the last pacing stimulus). The shock potential gradient field was orthogonal to the dispersion of refractoriness. Activation was mapped with 121 electrodes covering 4 x 4 cm of the right ventricular epicardium, and potential gradient and degree of recovery of excitability were estimated at the sites of reentry. Defibrillation thresholds (DFTs) were estimated by an up-down protocol for the same nine waveforms in eight dogs internally and in nine other dogs externally. DFT voltages for the different waveforms were positively correlated with the magnitude of shock potential gradient and negatively correlated with the recovery interval at the site at which reentry was induced by the waveform during paced rhythm for both internal (DFT = 1719 + 64.5VV - 11.1RI; R2 = 0.93) and external defibrillation (DFT = 3445 + 150VV - 22RI; R2 = 0.93). CONCLUSION: The defibrillation waveforms with the lowest DFTs were those that induced reentry at sites of low shock potential gradient, indicating efficacious stimulation of myocardium. Additionally, the site of reentry induced by waveforms with the lowest DFTs was in myocardium that was more highly recovered just before the shock, perhaps because this high degree of recovery seldom occurs during defibrillation due to the rapid activation rate during fibrillation.     

Biphasic waveform external defibrillation thresholds for spontaneous ventricular fibrillation secondary to acute ischemia.

OBJECTIVES: The goal of this study was to determine if the defibrillation threshold (DFT) after spontaneous ventricular fibrillation (VF) secondary to acute ischemia differs from the DFT for electrically induced VF in the absence of ischemia in anesthetized, closed-chest dogs and pigs. BACKGROUND: The efficacy of external defibrillators has been tested mainly in animals and humans using E-VF, yet external defibrillators are often used in patients to halt S-VF. METHODS: Protocol 1: biphasic truncated exponential (BTE) waveform shocks were delivered through electrodes placed in an anterior-anterior (A-A) position (left and right lateral thorax) in nine dogs. After measuring the E-VF DFT, acute ischemia was induced with an angioplasty balloon in either the left anterior descending or left circumflex coronary artery, and the S-VF DFT was determined. Protocol 2: in a group of 12 pigs, the E-VF DFT and S-VF DFT were determined for electrodes in the A-A position and in the anterior-posterior position (A-P). Protocol 3: the E-VF DFT was determined in seven pigs. Then up to three shocks 1.5x the E-VF DFT were delivered to S-VF. If defibrillation did not occur, a step-up protocol was used until defibrillation occurred. RESULTS: Protocol 1: the DFT for E-VF was 65 +/- 28 J (mean +/- SD) compared with 226 +/- 97 J for S-VF, p < 0.05. Protocol 2: the DFT was 152 +/- 58 J for E-VF and 315 +/- 123 J for S-VF for A-A electrodes. The DFT was 100 +/- 43 J for E-VF and 206 +/- 114 J for S-VF for A-P electrodes. Protocol 3: 11/37 shocks of strength 1.5x E-VF DFT (182 +/- 40 J) stopped the arrhythmia. The episodes of S-VF not halted by these shocks required energy levels of up to 400 J for defibrillation. CONCLUSIONS: External defibrillation of S-VF induced by acute ischemia requires significantly more energy than VF induced by 60-Hz current in the absence of ischemia. A safety margin >1.5x the DFT for electrically induced VF may be necessary in BTE external defibrillators to defibrillate S-VF.     

Activation sequences following failed atrial defibrillation

OBJECTIVES: The purposes of this study were to examine the first activations following atrial defibrillation shocks to help understand how and where atrial fibrillation (AF) relapsed following failed shocks and to assess the difference in postshock activation between failed and successful shocks. BACKGROUND: While many studies have investigated the mechanism of ventricular defibrillation, much less is known about the mechanisms of AF. METHODS: Sustained AF was induced electrically after pericardial infusion of methylcholine in 10 sheep. Biphasic subthreshold shocks were delivered to three configurations: right atrium to distal coronary sinus (RA-CS), sequential shocks with RA-CS as the first pathway followed by proximal CS to superior vena cava as the second pathway (Sequential), and right ventricle to superior vena cava plus can (V-triad). In eight sheep, global atrial mapping was performed with 504 electrodes spaced 3 to 4 mm apart. RESULTS: Earliest postshock activations mostly arose from the left atrium for V-triad but arose from either atrium for RA-CS and Sequential. Preshock AF cycle lengths were significantly shorter at the earliest activation sites than at seven of eight other sites globally distributed over both atria. In all type B successful episodes in which one or more rapid activations occurred after the shock and in 50 of the 72 failed episodes analyzed, activation fronts spread away from the earliest site in a focal pattern, and discrete nonfragmented activation complexes were present in the first derivatives of the electrograms. In the other 22 failed episodes, earliest activation fronts spread in a nonfocal pattern, and earliest postshock electrogram derivatives were fractionated. To better interpret the activation pattern in the fragmented regions, a 504 electrode plaque with 1.5-mm electrode spacing was placed on the right atrial appendage in two additional sheep. In 11 of 108 failed episodes, earliest postshock activation appeared inside the plaque and spread in a focal pattern with nonfragmented electrogram derivatives in 10 episodes and in a reentrant pattern with fragmented electrogram derivatives in the other. CONCLUSIONS: (1) The electrode configuration influenced the location of earliest postshock activation. (2) Earliest postshock activation occurred where the preshock AF cycle length was short. (3) Earliest activations following all type B successful and most failed episodes were not fragmented and spread in a focal pattern. (4) The region of earliest postshock activation in the failed episodes without a focal postshock activation pattern exhibited regions of fragmented electrogram derivatives that may represent conduction block and possibly reentry.     

Dysrhythmias after direct-current cardioversion

The success rate of direct-current (DC) countershocks and postshock arrhythmias are of concern for the design of automatic devices. Results of 112 DC shocks for induced ventricular tachycardia/fibrillation (VT/VF) (n = 99) or atrial fibrillation (AF) were analyzed. Clinical and arrhythmia characteristics were related to the success rate of DC shocks as well as postshock arrhythmias. Sixty-one patients were men and 14 were women; mean age was 52 +/- 15 years. Coronary artery disease was present in 56 patients and cardiomyopathy in 4. The other patients had no apparent structural heart disease. The success rate of transchest DC shocks for VT and VF were identical. The first DC shock interrupted 80% of VT and VF episodes. All episodes were terminated by 4 or fewer DC shocks. A single DC shock changed morphologic pattern or rate of 4 episodes of VT. Asystole after VT/VF (1,900 +/- 960 ms) was longer than after atrial fibrillation (1,150 +/- 470 ms, p less than 0.01). VT/VF recurred (within 3 minutes) after 26 of 99 initially successful DC shocks, requiring repeat shocks in 2 cases. Sinus bradycardia (n = 18) or high degree atrioventricular block (n = 11) necessitated rate support pacing in 10 patients. Antiarrhythmic drugs did not prevent postshock tachycardias, but facilitated the development of bradycardias. In conclusion, reliable and continuous analysis of cardiac rhythm after discharge is mandatory to enable automatic devices to correct unsuccessful discharges or recurring VT/VF. In addition, demand pacing capability is desirable to prevent severe bradycardia after DC shocks in patients receiving antiarrhythmic drugs.     

置入型心律转复除颤器52例术中除颤阈值的测定及术后随访

目的 探讨置入型心律转复除颤器(ICD)置入术中除颤阈值(DFT)的测定方法并观察术后随访结果.方法 52例置入ICD患者,其中单腔ICD 25例(48.08%),双腔ICD 23例(44.23%),三腔ICD 4例(7.69%).置入术中用测定除颤安全范围(DSM)方法进行DFT测定,并对患者进行定期随访.结果 52例ICD置入术中,测得DFT为(13.27±2.95)J,DSM为(17.40±2.89)J,手术中无严重并发症发生.52例中,38例出现恶性室性心律失常,其中469次为非持续性(可自行终止)室性心动过速(VT),持续性VT发作265次;经抗心动过速起搏治疗1阵转复成功245次(92.45%),2阵转复成功13次(4.91%),抗心动过速起搏治疗转复未成功经电转复7次(2.64%),均经低能量电转复成功.心室颤动(VF)发作141次均成功识别,其中14次在释放治疗前VF自行终止.127次VF经电除颤治疗,经电除颤治疗1次成功116次(91.34%),除颤能量为(12.84±3.18)J,2次成功11次(8.66%),除颤能量为(16.36±2.34)J.结论 应用DSM测定进行ICD置入术中DFT测定安全可行.     

Post-shock synchronized pacing in isolated rabbit left ventricle: evaluation of a novel defibrillation strategy

Introduction: A failed near-threshold defibrillation shock is followed by an isoelectric window (IEW) and rapid repetitive responses that reinitiate ventricular fibrillation (VF). We hypothesized that properly timed (synchronized) postshock pacing stimuli (SyncP) may capture the recovered tissues during the repetitive responses and prevent postshock reinitiation of VF, resulting in improved defibrillation efficacy.
Methods and Results: We explored the effect of postshock SyncP on defibrillation efficacy in isolated rabbit hearts (n = 12). Optical recording-guided real-time detection and electrical stimulation (5 mA) of recovered tissues in anterior/posterior left ventricle (LV) were performed following IEW. The IEW duration was found to be 69 ± 13 ms. With the same shock strength, successful and failed defibrillation episodes were associated with 50% and 15% of the myocardium, respectively, captured by the SyncP (P < 0.001). Electrical stimulation from the posterior LV resulted in 75% of episodes capturing myocardium, as compared with anterior LV stimulation (55%; P < 0.01) and higher successful defibrillation rate (14%, posterior vs. 3%, anterior LV). The overall success in terminating VF by postshock SyncP was approximately 10%. The causes for failed myocardium capture by postshock SyncP included lack of IEW after low-strength shock (42.9%), incorrect locations of reference site (25.7%) and pacing electrodes (17.9%), and others, such as wave breakthroughs (13.5%).
Conclusion: Postshock SyncP was feasible and the larger the myocardium captured area, the more likely was the successful defibrillation. Postshock SyncP delivered to the posterior LV was more effective than anterior LV to terminate VF.     

Improvement of defibrillation efficacy with preshock synchronized pacing

INTRODUCTION: We previously demonstrated that wavefront synchronization by spatiotemporal excitable gap pacing (Sync P) is effective at facilitating spontaneous termination of ventricular fibrillation (VF). Therefore, we hypothesized that a spatiotemporally controlled defibrillation (STCD) strategy using defibrillation shocks preceded by Sync P can improve defibrillation efficacy. METHOD AND RESULTS: We explored the STCD effects in 13 isolated rabbit hearts. During VF, a low-voltage gradient (LVG) area was synchronized by Sync P for 0.92 second. For Sync P, optical action potentials (OAPs) adjacent to four pacing electrodes (10 mm apart) were monitored. When one of the electrodes was in the excitable gap, a 5-mA current was administered from all electrodes. A shock was delivered 23 ms after the excitable gap when the LVG area was unexcitable. The effects of STCD was compared to random shocks (C) by evaluating the defibrillation threshold 50% (DFT(50); n = 35 for each) and preshock coupling intervals (n = 208 for STCD, n = 172 for C). Results were as follows. (1) Sync P caused wavefront synchronization as indicated by a decreased number of phase singularity points (P < 0.0001) and reduced spatial dispersion of VF cycle length (P < 0.01). (2) STCD decreased DFT(50) by 10.3% (P < 0.05). (3) The successful shocks showed shorter preshock coupling intervals (CI; P < 0.05) and a higher proportion of unexcitable shock at the LVG area (P < 0.001) than failed shocks. STCD showed shorter CIs (P < 0.05) and a higher unexcitable shock rate at LVG area (P < 0.05) than C. CONCLUSION: STCD improves defibrillation efficacy by synchronizing VF activations and increasing probability of shock delivery to the unexcitable LVG area.     

Preshock phase singularity and the outcome of ventricular defibrillation

BACKGROUND: Phase singularity (PS) is a topological defect that serves as a source of ventricular fibrillation (VF). Whether or not the quantity of preshock PS determines defibrillation outcome is unclear. OBJECTIVE: The purpose of this study was to test the hypothesis that the number of PSs at the time of shock is an important factor that determines the shock outcome. METHODS: Isolated, perfused rabbit hearts (n = 7) were optically mapped with a potentiometric dye (di-4-ANNEPS). Shocks were delivered during short (10 seconds) and long (1 minute) VF, and the outcome was classified as successful type A (immediate termination), type B (postshock repetitive responses before termination), and unsuccessful. RESULTS: When shock strengths of 50% probability of successful defibrillation (DFT50) +/- 50 V were given in short VF, the types A and B and unsuccessful shocks were associated with a preshock PS number of 0.3 +/- 0.4, 1.4 +/- 0.3, and 1.5 +/- 0.4 (P <.01 by analysis of variance) and shock strengths of 205 +/- 77, 207 +/- 65, and 173 +/- 74 V (P <.01), respectively. When the same shocks were applied during long VF, the PS numbers were 1.7 +/- 0.5, 3.0 +/- 0.5, and 3.5 +/- 0.6, respectively (P <.01), and the shock strengths were 282 +/- 100, 283 +/- 135, and 256 +/- 126 V, respectively (P <.01). If we only analyze shocks with strength at DFT(50), the preshock PS number was still significantly different for short VF (0.6 +/- 0.5, 1.6 +/- 0.9, and 1.5 +/- 0.8; P <.05) and for long VF (1.4 +/- 0.5, 2.7 +/- 0.6, and 2.7+/-1.3; P <.05), respectively. All preshock PSs were eliminated by shocks. However, rapid repetitive activity was then reinitiated in unsuccessful and type B successful shocks but not in type A successful shocks. CONCLUSIONS: A low number or an absence of preshock PS was associated with type A successful defibrillation. There was no difference in preshock PS numbers between unsuccessful and type B successful defibrillation.     

The effects of biphasic and conventional monophasic defibrillation on postresuscitation myocardial function.

OBJECTIVES: The purpose of this study was to compare the effects of biphasic defibrillation waveforms and conventional monophasic defibrillation waveforms on the success of initial defibrillation, postresuscitation myocardial function and duration of survival after prolonged ventricular fibrillation (VF). BACKGROUND: We have recently demonstrated that the severity of postresuscitation myocardial dysfunction was closely related to the magnitude of the electrical energy of the delivered defibrillation shock. In the present study, the effects of fixed 150-J low-energy biphasic waveform shocks were compared with conventional monophasic waveform shocks after prolonged VF. METHODS: Twenty anesthetized, mechanically ventilated domestic pigs were investigated. VF was induced with an AC current delivered to the right ventricular endocardium. After either 4 or 7 min of untreated ventricular fibrillation (VF), the animals were randomized for attempted defibrillation with up to three 150-J biphasic waveform shocks or conventional sequence of 200-, 300- or 360-J monophasic waveform shocks. If VF was not reversed, a 1-min interval of precordial compression preceded a second sequence of up to three shocks. The protocol was repeated until spontaneous circulation was restored or for a total of 15 min. RESULTS: Monophasic waveform defibrillation after 4 or 7 min of untreated VF resuscitated eight of 10 pigs. All 10 pigs treated with biphasic waveform defibrillation were successfully resuscitated. Transesophageal echo-Doppler, arterial pressure and heart rate measurements demonstrated significantly less impairment of cardiovascular function after biphasic defibrillation. CONCLUSIONS: Lower-energy biphasic waveform shocks were as effective as conventional higher energy monophasic waveform shocks for restoration of spontaneous circulation after 4 and 7 min of untreated VF. Significantly better postresuscitation myocardial function was observed after biphasic waveform defibrillation.     

Evidence that activation following failed defibrillation is not caused by triggered activity

BACKGROUND: Earliest postshock activation following failed defibrillation shocks slightly lower than the defibrillation threshold (DFT) in large animals appears to arise from a focus. We tested the hypothesis that these foci are caused by early or delayed afterdepolarizations (EADs or DADs) by performing epicardial electrical mapping and giving the EAD inhibitor pinacidil or the DAD inhibitor flunarizine to see if the foci were extinguished or altered in timing or location. METHODS AND RESULTS: A sock containing 504 electrodes was placed over the entire ventricular epicardium of 12 open-chested pigs. After the DFT was determined and additional shocks given, pinacidil was administered to 6 pigs and flunarizine to 6 pigs. Then, the DFT was again determined and additional shocks were given. Pinacidil significantly shortened the effective refractory period (ERP) (162 +/- 16 vs 130 +/- 28 msec) and action potential duration (APD(90)) (179 +/- 6 vs 149 +/- 19 msec) and significantly increased the peak frequency of the power spectrum of a left ventricle (LV) electrode during ventricular fibrillation (VF) (9.3 +/- 0.6 vs 10.5 +/- 1.0 Hz), while flunarizine did not significantly alter the ERP (162 +/- 8 vs 167 +/- 18 msec) or APD(90) (187 +/- 12 vs 191 +/- 20) but significantly reduced the peak frequency (9.2 +/- 0.5 vs 7.5 +/- 1.0 Hz). These findings suggest the drugs had their expected electrophysiological effects. However, the DFT was not significantly changed by either drug. Following the same strength shock 10% below the predrug DFT, earliest postshock activation arose in a focal epicardial pattern from the anterior-apical LV both before and after the drugs. The time from the shock until the appearance of this activation was not significantly different before and after either drug. CONCLUSION: The lack of change in DFT as well as the lack of change in the incidence, location, and timing of the postshock focus with sub-DFT strength shocks before and after pinacidil and flunarizine provide evidence that these foci are not caused by triggered activity.     

Transmural and endocardial Purkinje activation in pigs before local myocardial activation after defibrillation shocks.

BACKGROUND: Earliest recorded postshock myocardial activations in pigs originate in the subepicardium of the apex and lateral free wall of the left ventricle (LV) 30-90 ms after the shock. OBJECTIVE: The purpose of this study was to determine whether the Purkinje system is a candidate for the source of postshock activations by performing endocardial and transmural postshock activation mapping. METHODS: In five pigs, 32 plunge needles with 12 electrodes (1-mm spacing) were inserted into the LV apex and lateral free wall. Up to 70 plunge needles with six electrodes (2-mm spacing) were spread throughout the remainder of the LV, while 9-12 plunge needles with four electrodes (2-mm spacing) were inserted into the right ventricle. A basket catheter with 32 bipolar recording sites was inserted into the LV. Defibrillation-threshold (DFT)-level shocks were delivered during 10 episodes of electrically induced ventricular fibrillation. Electrograms of postshock activation cycles were analyzed for Purkinje and myocardial activations. RESULTS: Purkinje activations were recorded before local myocardial activation in 9% of basket electrograms and in 15% of plunge needles during the first postshock activation cycle. Purkinje activations were identified during the first and subsequent several postshock activation cycles in at least one basket and one needle electrogram in 96% and 98% of defibrillation episodes, respectively. CONCLUSIONS: The Purkinje system is active during the early postshock activation cycles after DFT-level shocks. Further studies are required to determine whether activation initiates in the Purkinje system or whether it is activated by the myocardium or by Purkinje-myocardial junctional cells.     

Comparison of activation during ventricular fibrillation and following unsuccessful defibrillation shocks in open-chest dogs

The purpose of this study was to map in detail the spread of activation away from sites of early postshock excitation following unsuccessful defibrillation to determine whether these activation fronts are the unaltered continuation of activation fronts present just before the shock. We recorded simultaneously from 120 bipolar electrodes on 40 plunge needles in a 20 x 35 x 5-mm volume of tissue of the right ventricular outflow tract immediately before and after shocks of 190-350 V were given via electrodes on the right atrium and left ventricular apex to six open-chest dogs with electrically induced ventricular fibrillation. For 20 shocks approximately 100 V below the defibrillation threshold, the site of earliest recorded activation following the shock was near the center of the mapped region. At the earliest recorded activation sites, there was an isoelectric window in the immediate postshock period lasting 42 +/- 15 msec after which activation fronts either spread away from a site in all directions in a focal pattern (12 episodes) or else spread away in only one direction (eight episodes). Comparison of activation patterns immediately before and after the shock revealed that in 18 of the 20 episodes, the location and pathway of activation fronts after the shock were markedly different from those before the shock. The preshock intervals at the sites of earliest activation following the shock, that is, the interval between the last activation at the site and the time of the shock, were not randomly distributed but were similar, averaging 64 +/- 11 msec, and were negatively correlated with the isoelectric postshock window (r = -0.70, p = 0.0001). These findings indicate that the presence and the site of origin of activation fronts after the shock are influenced by at least two factors: the shock itself and the electrophysiological state of the myocardium at the time of the shock. Thus, epicardial shocks approximately 100 V below the defibrillation threshold markedly alter the activation sequences of fibrillation but are unsuccessful because the activation fronts following the shock reinitiate fibrillation.     

Monophasic versus biphasic transthoracic countershock after prolonged ventricular fibrillation in a swine model

OBJECTIVE: We sought to compare the defibrillation efficacy of a low-energy biphasic truncated exponential (BTE) waveform and a conventional higher-energy monophasic truncated exponential (MTE) waveform after prolonged ventricular fibrillation (VF). BACKGROUND: Low energy biphasic countershocks have been shown to be effective after brief episodes of VF (15 to 30 s) and to produce few postshock electrocardiogram abnormalities. METHODS: Swine were randomized to MTE (n = 18) or BTE (n = 20) after 5 min of VF. The first MTE shock dose was 200 J, and first BTE dose 150 J. If required, up to two additional shocks were administered (300, 360 J MTE; 150, 150 J BTE). If VF persisted manual cardiopulmonary resuscitation (CPR) was begun, and shocks were administered until VF was terminated. Successful defibrillation was defined as termination of VF regardless of postshock rhythm. If countershock terminated VF but was followed by a nonperfusing rhythm, CPR was performed until a perfusing rhythm developed. Arterial pressure, left ventricular (LV) pressure, first derivative of LV pressure and cardiac output were measured at intervals for 60 min postresuscitation. RESULTS: The odds ratio of first-shock success with BTE versus MTE was 0.67 (p = 0.55). The rate of termination of VF with the second or third shocks was similar between groups, as was the incidence of postshock pulseless electrical activity (15/18 MTE, 18/20 BTE) and CPR time for those animals that were resuscitated. Hemodynamic variables were not significantly different between groups at 15, 30 and 60 min after resuscitation. CONCLUSIONS: Monophasic and biphasic waveforms were equally effective in terminating prolonged VF with the first shock, and there was no apparent clinical disadvantage of subsequent low-energy biphasic shocks compared with progressive energy monophasic shocks. Lower-energy shocks were not associated with less postresuscitation myocardial dysfunction.     

Effects of shock strengths on ventricular defibrillation failure

BACKGROUND: The mechanism of defibrillation is controversial. Reentry appearing immediately after the shock has been shown to be responsible for defibrillation failure in some studies while other studies have demonstrated that a rapid train of focal activations with the first focus appearing >50 ms after the shock is responsible for failed defibrillation. We tested the hypothesis that both patterns can occur, but at different shock strengths. METHODS AND RESULTS: Biphasic 6/4 ms shocks of 100-900 V in 100-V increments were given after 10 s of ventricular fibrillation from electrodes in right ventricular apex and right atrium in five isolated pig hearts. Transmembrane activity was optically mapped from the anterior and posterior epicardium using two CCD cameras. The defibrillation threshold (DFT) was 786+/-199 V. The interval from the shock to the earliest post-shock activation was zero for shocks <400 V but increased with increasing shock voltage to 62+/-6 ms at 800 V. The number of post-shock phase singularities, which is related to reentry incidence, decreased continuously from pre-shock values for 100-V shocks to zero as the shock strength increased to 600 V. Focal activations were observed after shocks >600 V with no epicardial reentry present. CONCLUSION: Reentry is responsible for defibrillation failure for low-strength shocks. As the shock strength approaches the DFT, a focal epicardial activation pattern becomes responsible for failed defibrillation. Thus, the mechanism of defibrillation failure depends on shock strength, with focal activation as the mechanism for the clinically important near-DFT strength shocks.