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Notes: Mapping After Monophasic and Biphasic Shocks. Introduction: The reason for the increased defibrillation efficacy of biphasic shocks over monophasic shock is not definitely known. Methods and Results: In six anesthetized pigs, we mapped the epicardium after transvenous defibrillation shocks to compare the activation patterns following successful biphasic shocks with unsuccessful monophasic shocks of the same voltage. The heart was exposed and a 510-electrode sock with approximately 4-mm interelectrode spacing was pulled over the entire ventricular epicardium and sutured to the pericardium. Defibrillation catheters were placed in the right ventricular apex and in the superior vena cava. Paired monophasic 12 msec and biphasic 6/6 msec defibrillation shocks were given using an up-down protocol to keep shock strength between the defibrillation thresholds for the two waveforms so that the biphasic shock was successful while the monophasic shock was not. Activation fronts immediately following 60 paired shocks were recorded and analyzed by animated maps of the first derivative of the electrograms. The ventricles were divided into apical (I), middle (II), and basal (III) thirds, and early sites, i.e., the sites from which activation fronts first appeared on the epicardium following the shock, were grouped according to their location. Postshock intervals, i.e., the time from the shock until earliest epicardial activation occurred, were also determined. No ectopic activation fronts followed the shock in 20 biphasic episodes. In the other 40 paired episodes, the number of early sites was smaller after biphasic shocks than after monophasic shocks (monophasic: 198 (total), 3.3 ± 0.9 (mean ± SD) per shock episode; biphasic: 67, 1.1 ± 1.0, P 〈 0.05]. For biphasic but not monophasic shocks, early sites were less likely to arise from the middle (II) and basal (III) thirds than from the apical third (I) [monophasic: I: 84 (42%), II: 68 (34%), III: 46 (23%); biphasic: I: 49 (73%), II: 10 (15%), III: 8 (12%), P 〈 0.05]. Postshock intervals were significantly shorter for monophasic shocks (54 ± 14 msec) than for biphasic shocks (75 ± 23 msec, P 〈 0.05). Conclusion: The decreased number of activation fronts and the longer delay following the shock for the earliest epicardial appearance of those activation fronts that do occur may be responsible for the increased defibrillation efficacy for biphasic shocks.

Notes: Optimal Monophasic and Biphasic Waveforms. Introduction: The truncated exponential waveform from an implantable cardioverter defibrillator can be described by three quantities: the leading edge voltage, the waveform duration, and the waveform time coastant (τs). The goal of this work was to develop and test a mathematical model of defibrillation that predicts the optimal durations for monophasic and the first phase of biphasic waveforms for different τs values. In 1932, Blair used a parallel resistor-capacitor network as a model of the cell membrane to develop an equation that describes stimulation using square waves. We extended Blair's model of stimulation, using a resistor-capacitor network time constant (τm), equal to 2.8 msec, to explicitly account for the waveform shape of a truncated exponential waveform. This extended model predicted that for monophasic waveforms with τs of 1.5 msec, leading edge voltage will be constant for waveforms 2 msec and longer; for τs of 3 msec, leading edge voltage will be constant for waveforms 3 msec and longer; for τs of 6 msec, leading edge voltage will be constant for waveforms 4 msec and longer. We hypothesized that the best phase 1 of a biphasic waveform is the best monophasic waveform. Therefore, the optimal first phase of a biphasic waveform for a given τs is the same as the optimal monophasic waveform. Methods and Results: We tested these hypotheses in two animal experiments. Part I: Defibrillation thresholds were determined for monophasic waveforms in eight dogs. For τs of 1.5 msec, waveforms were truncated at 1, 1.5, 2, 2.5, 3, 4, 5, and 6 msec. For τs of 3 msec, waveforms were truncated at 1, 2, 3, 4, 5, 6, and 8 msec. For τs of 6 msec, waveforms were truncated at 2, 3, 4, 5, 6, 8, and 10 msec. For waveforms with τs, of 1.5, leading edge voltage was not significantly different for the waveform durations of 1.5 msec and longer. For waveforms witb τs of 3 msec, leading edge voltage was not significantly different for waveform durations of 2 msec and longer. For waveforms with τs of 6 msec, there was no significant difference in leading edge voltage for the waveforms tested. Part II: Defibrillation thresholds were determined in another eight dogs for the same three τs values For each value of τs, six biphasic waveforms were tested: 1/1, 2/2, 3/3, 4/4, 5/5, and 6/6 msec. For waveforms with τs of 1.5 msec, leading edge voltage was a minimum for the 2/2 msec waveform. For waveforms with τs of 3 msec, leading edge voltage was a minimum for the 3/3 msec waveform. For waveforms with τs of 6 msec, leading edge voltage was a minimum and not significantly different for the 3/3, 4/4, 5/5, and 6/6 msec waveforms. Conclusions: The model predicts the optimal monophasic duration and the first phase of a biphasic waveform to within 1 msec as τs varies from 1.5 to 6 msec: for τs equal to 1.5 msec, the optimal monophasic waveform duration and the optimal first phase of a biphasic waveform is 2 msec, for τs equal to 3.0 msec, the optimal duration is 3 msec, and for τs equal to 6 msec, the optimal duration is 4 msec. For both monophasic and biphasic waveforms, optimal waveform duration shortens as the waveform time constant shortens.

Notes: Responses of Transmembrane Potential During a Shock. Introduction: The purpose of this investigation was to study the transmembrane potential changes (δVm) during extracellular electrical field stimulation. Methods and Results: Vm was recorded in seven guinea pig papillary muscles in a tissue hath by a double-barrel microelectrode with one barrel in and the other just outside a cell while shocks were given across the bath. The short distance (15 to 30 μm) between the two microelectrode tips and alignment of the tips parallel to the shock electrodes eliminated the shock artifact. Following ten SI stimuli, an S2 shock field created by a 10-msec square wave was delivered during the action potential plateau or during diastole through shock electrodes 1 cm on either side of the tissue. Four shock strengths creating field strengths of 1.7 ± 0.1, 2.9 ± 0.2, 6.1 ± 0.6. and 8.8 ± 0.9 V/cm were given for the same impalement. Both shock polarities were given at each shock strength. For shocks delivered during the action potential plateau, the magnitudes of the peak δVm caused by the above four potential gradients were 21.1 ± 8.2, 33.6 ± 13.6, 49.9 ± 24.2, and 52.3 ± 28.0 mV (P 〈 0.05 among the four groups) for the shocks causing depolarization and 37.9 ± 14.2,56.6 ± 16.4,83.1 ± 19.4. and 92.9 ± 29.1 mV (P 〈 0.05 among the four groups) for the shocks causing hyperpolarization. Though δVm increased as potential gradients increased, the relationship was not linear. The magnitude of hyperpolarization was 1.9 ± 0.5 times that of depolarization when the shock polarity was reversed (P 〈 0.05). As potential gradients increased from 1.7 ± 0.1 to 8.8 ± 0.9 V/cm, the time constant of the membrane response decreased significantly from 3.5 ± 1.8 to 1.6 ± 0.7 msec for depolarizing shocks and from 6.0 ± 3.1 to 3.4 ± 1.9 msec for hyperpolarizing shocks (P 〈 0.01 vs depolarizing shocks). For shocks delivered during diastole, hyperpolarizing shocks induced triphasic changes in Vm during the shock, i.e., initial hyperpolarization, then depolarization, followed again by hyperpolarization. Conclusion: During the action potential plateau, the membrane response cannot be represented by a classic passive RC membrane model. During diastole, activation upstrokes occur even during hyperpolarization caused by shocks creating potential gradients between aproximately 2 and 9 V/cm.

Notes: Adrenergic Effects on VF. Introduction: We hypothesized that drugs which alter ventricular refractoriness or excitability produce quantifiable changes in ventricular fibrillation. Methods and Results: We used a 528-channel mapping system to quantify the effects of the beta-antagonist, propranolol, and the beta-agonist, isoproterenol, on activation patterns in ventricular fibrillation. A plaque of 506 (22 × 23) electrodes spaced 1.12 mm apart and covering about 5% of the ventricular epicardium was sewn to the anterior right ventricle in 18 pigs (30 kg). Propranolol (0.25 to 0.4 mg/kg) increased the refractory period at a right ventricular epicardial site while isoproterenol (3 to 5 μg/min) shortened it. Ventricular fibrillation was induced by programmed stimulation, and unipolar electrograms were recorded from the 506 plaque electrodes for 2 seconds beginning 1, 15, and 30 seconds after the onset of fibrillation. Active epicardial recording sites were identified from the first derivative of the unipolar potentials (dV/dt) detected at each electrode. Then, neighboring active sites were grouped into activation fronts by computer analysis. In six pigs the effect of repeated inductions of ventricular fibrillation was assessed by comparing ventricular fibrillation after saline with a preceding control episode of fibrillation. Each activation front excited 40%± 46% of the mapped region before blocking. No changes were observed with saline and multiple inductions of fibrillation. In another six pigs, ventricular fibrillation after propranolol was compared with a preceding control episode of fibrillation. Ventricular fibrillation alter propranolol exhibited a decreased activation rate per epicardial recording site and fewer activation fronts per second. There was no change in the amount of tissue excited by each activation front or the number of reentry cycles per activation front compared with control. In addition, there was no change in the maximum negative dV/dt detected per activation at an epicardial site. In six pigs ventricular fibrillation during isoproterenol was compared with control episodes of ventricular fibrillation before and 45 minutes after washout of the drug. The control episodes of fibrillation were not different from each other. Compared with control, ventricular fibrillation during isoproterenol exhibited an increased activation rate per epicardial site, an increased amount of tissue excited by each activation front, and an increased maximum negative dV/dt for each activation. There was no change in the number of activation fronts per second or the number of reentry cycles per activation front compared with control. Conclusions: Quantitative analysis revealed that propranolol and isoproterenol do not have symmetrically opposite effects on ventricular fibrillation. Propranolol decreased the number of activation fronts while isoproterenol increased the amount of tissue excited by each activation front. Thus, drugs that alter ventricular refractoriness or excitability alter ventricular fibrillation.

Notes: Influence of VF Duration on Defibrillation Efficacy. introduction: While the defibrillation threshold has been reported to increase with ventricular fibrillation (VF) duration for monophasic waveforms, the effect of VF duration for biphasic waveforms is unknown. Methods and Results: The ED 50 requirements (the 50% probability of defibrillation success) for an endocardial lead system, which included a subcutaneous array, were determined by logistic regression using a recursive up-down algorithm for a biphasic waveform ((6/6 msec). The study was performed in two parts, each with eight pigs. In part 1, ED 50 was compared for shocks delivered after 10 seconds of VF and for shocks delivered after 20 seconds of VF following a failed first shock at 10 seconds. Energy at ED 50 decreased from 6.5 ± 0.9, J for shocks delivered after 10 seconds of VF to 4.9 ± 0.8, J (P 〈 0.01) for shocks delivered after 20 seconds. To determine if improved second shock efficacy was a result of preconditioning by the failed first shock or a function of VF duration, part 2 of the study compared defibrillation efficacy between shocks delivered after 10 seconds of VF with shocks delivered after 20 seconds of VF with and without a failed first shock at 10 seconds. Mean energy at ED 50 decreased from 10.1 ± 2.4, J for shocks delivered after 10 seconds of VF to 7.9 ± 2.4 J (P 〈 0.01) and 7.5 ± 3.2 J (P 〈 0.01) for shocks delivered after 20 seconds of VF with and without a failed first shock, respectively. The mean energy at KD 50 for shocks delivered after 20 seconds of VK with and without a failed first shock was not significantly different (P = 0.53). A strong linear correlation for energy at ED 50 was found between shocks delivered after 10 seconds of VF and shocks delivered after 20 seconds of VF following a failed first shock (r = 0.95, P 〈 0.01). Conclusion: (1) As opposed to monophasic shocks, ED 50 is significantly lower for biphasic shocks delivered after 20 seconds of VF compared with shocks delivered after 10 seconds of VF in pigs. (2) An unsuccessful biphasic shock in pigs does not affect the defibrillation efficacy for a subsequent shock. (3) ED 50 for a biphasic shock delivered after 20 seconds of VK is linearly related to ED 50 for a shock delivered after 10 seconds of VK.

Notes: The two goals of this study were (1) to develop a closed-chest animal model of monomorphic ventricular tachycardia; and (2) to investigate the effect of dual site pacing on inducibility of ventricular tachycardia. In the first part of the study, 10 of 14 sheep underwent successful induction of myocardial infarction by temporary balloon occlusion of the left anterior descending coronary artery. After a follow-up period of 21–43 days, sustained monomorphic ventricular tachycardia could be induced during programmed electrical stimulation using a “clinical” stimulation protocol in 8 of the 10 sheep. The number of ventricular tachycardia episodes per animal varied between 5 and 70. Ventricular fibrillation was never induced during programmed electrical stimulation. Ventricular tachycardia episodes lasted from 30 seconds up to 15 minutes and were terminated by antitachycardia pacing or DC cardioversion. In the second part of the study, the effect of dual site stimulation on ventricular tachycardia inducibility was investigated. High current stimuli from an area within the infarcted zone were given with the S1 programmed stimulation protocol. This dual site stimulation showed no effect on ventricular tachycardia induction during programmed electrical stimulation. This animal model shows a high induction rate of sustained monomorphic ventricular tachycardia in the chronic phase of myocardial infarction. The high incidence of ventricular tachycardia inducibility provides a reliable tool to study new techniques for the prevention of ventricular tachyarrhythmias.

Notes: The defibrillation threshold is markedly reduced very early following the initiation of ventricular fibrillation. The purpose of this study was to determine if the same finding holds true for atrial defibrillation. Sustained, reproducible AF was induced with programmed atrial pacing using acetyl-β-methylcholine chloride (40–640 μL/min) in six adult sheep (heart weight 245–300 g). Seven timing intervals (125 ms, 200 ms, 1 s, 3 s, 10 s, 30 s, and 5 min after AF induction) and two lead configurations: (1) RA as cathode and CS as anode; and (2) RA as cathode and RV apex as anode were tested. Single capacitor biphasic waveforms (3/1 ms) were delivered and atrial defibrillation thresholds (ADFTs) were determined in random order. No significant differences in leading edge voltage and total energy were detected for the RA-CS configuration for the seven timing intervals. For the RA-RV configuration, a significant difference was detected comparing the voltage for 125 ms to the 5-minute timing interval. For all times except 125 ms, the RA-RV threshold was significantly higher than the RA-CS level. In contrast to ventricular defibrillation, the ADFT does not change significantly within the first 5 minutes after the initiation of AF for the RA-CS configuration. However, if the shock is given very early (125 ms after AF induction) with the RA-RV configuration, the ADFT is lowered almost to the RA-CS level.

Notes: Abstract Ventricular fibrillation, a loss of synchronus electrical activity in the heart which leads to hemodynamic collapse, is a leading cause of death. Because of the devastating personal and societal effects of this phenomenon, the automatic cardioverter-defibrillator has been developed for automatic detection and termination of the arrhythmia and is in widespread clinical use. Advances in circuits, leads, waveforms, and signal processing along with increased knowledge of the mechanisms of fibrillation have led to continuing improvements in this device, extending its use to many patients. A device has also been developed for the automatic or semiautomatic treatment of atrial fibrillation, an arrhythmia less life-threatening than ventricular fibrillation, but still a serious health problem. Continued improvement of these devices and the development of qualitatively new approaches hold great promise for exciting therapeutic advances in this area.

Notes: Prevention of Action Potentials by Electrical Stimulation. Introduction: This study investigated if action potentials can be prevented by electrical field stimuli of long duration. Methods and Results: The transmembrane potential was recorded by a double-barrel micro-electrode during field stimulation given across a papillary muscle from 10 guinea pigs. After 10 stimuli (S) with a 200-msec S-S interval, a 400-msec square wave shock was given Just before or after the end of the effective refractory period following the 10th stimulus through electrodes 1 cm on either side of the papillary muscles. Another two stimuli (S' and S”) having the same 200-msec S-S interval were given during the shock pulse to test if the action potentials induced by these two stimuli could be prevented by the shock. The shock strength was increased until the shock field prevented the action potentials induced by the S' and S” stimuli. The resting membrane potential was −85.5 ± 2.9 mV. For shocks causing depolarization at the recording site, the field strength required to prevent S'- and S”-induced action potentials was 1.5 ± 0.4 V/cm, which depolarized the transmembrane potential to −55.3 ± 8.9 mV and −58.1 ± 7.2 mV from the resting membrane potential at the time of the S' and S” stimuli, respectively. The strength of shocks causing hyperpolarization required to prevent S'- and S”-induced action potentials was 5.0 ± 0.8 V/cm, which hyperpolarized the transmembrane potential to −105 ± 6.5 mV and −115.6 ± 6.9 mV from the resting membrane potential at the time of the S' and S” stimuli, respectively. Conclusion: Both depolarization and hyperpolarization caused by an electrical field can prevent action potentials.

Notes: Defibrillation Electrode Polarity. introduction: To test the hypothesis that the effect of shock polarity on defibrillation depends on waveform duration, this study determined strength-duration defibrillation curves of monophasic and biphasic truncated exponential waveforms for both polarities. Methods and Results: Defibrillation thresholds (DFTs) were obtained in 32 pigs for catheter electrodes in the right ventricle (RV) and superior vena cava (SVC) using a modified Purdue technique. Both electrode polarities were tested in five different protocols. In part 1, DFTs were determined with 1- to 14-msec monophasic waveforms. In parts 2, 3, and 4, DFTs were determined with two different sizes of SVC electrodes for biphasic waveforms with a phase 1 of 4 or 6 msec and a phase 2 ranging from 1 to 10 msec. In part 5, DFTs were tested for monophasic waveforms ranging from 2 to 11 msec and for biphasic waveforms with a phase 1 duration corresponding to each monophasic waveform and a phase 2 held constant at 1 msec. Mean DFTs for monophasic waveforms were significantly lower when the RV electrode was an anode than when it was a cathode for waveform durations ≥ 3 msec. For biphasic waveforms in which phase 2 was ≤ phase 1 in duration, no significant difference in mean DFT was observed when polarity was reversed. Even a phase 2 as short as 1 msec could eliminate the DFT difference between polarities observed with monophasic shocks. When phase 2 was ≥ 2 msec longer than phase 1, polarity did affect the DFT of biphasic waveforms: it affected the DFT similarly to a monophasic waveform of the same polarity as phase 2. Phase 1 duration and electrode size also affected the difference in DFT produced by changing the electrode polarity. Conclusions: For phase durations most commonly used clinically because of their low DFTs. reversing polarity changed defibrillation efficacy for monophasic but not biphasic shocks. For inefficient biphasic waveforms with phase 2 ≥ 2 msec longer than phase 1, the DFT was lower when the RV electrode was an anode during phase 2, similar to the polarity difference for monopbasic waveforms, suggesting that a long second phase of biphasic waveforms defibrillates in a similar fashion to monophasic waveforms.