Internal Defibrillation Threshold Research Articles

Abstract 9386: Ramp Biphasic Waveforms Have a Lower External Defibrillation Threshold

Introduction: We have previously shown that waveforms with an ascending ramp in both phases have a lower internal defibrillation threshold (DFT). The purpose of this study was to test whether waveforms with rectilinear, ascending and descending ramps in the second phase would reduce the DFT compared with a standard exponential biphasic waveform with external defibrillation shocks. Methods: In 6 pigs, DFTs were determined for 10 waveforms: a standard truncated exponential biphasic waveform with 60% tilt (Fig 1, #1) and 9 biphasic waveforms with an 8 ms ascending ramp 1st phase and one of 3 rectilinear, ascending ramp or descending ramp 2nd phases. The 3 rectilinear 2nd phases were: 1 ms, 200% of peak voltage of phase 1 (#2); 2 ms, same voltage as phase (#3); 3 ms, half the voltage of phase 1 (#4). The 3 ascending ramp 2nd phases were: 2 ms, 200% of voltage of phase 1(#5); 3 ms, same voltage as phase 1(#6); 4.5 ms, half the voltage of phase 1(#7). The 3 descending ramp 2nd phases were: 2 ms, 200% of voltage of phase 1(#8); 3 ms, same voltage as phase 1(#9); 4.5 ms, half the voltage of phase 1(#10). Results: Phase 2 ascending ramp (#7) and descending ramp (#8, #9) waveforms had the lowest DFTs, which were significantly smaller than for the truncated exponential waveform. (Fig 1, *indicates p<0.05). Conclusions: Waveforms with a ramp in phase 2 (#7, #8, #9) have a lower DFT.

Increase in Internal Defibrillation Threshold During Acute Myocardial Infarction

A 67-year-old man suffered an acute anteroseptal myocardial infarction complicated by multiple episodes of ventricular fibrillation, which were not systematically defibrillated by maximum, internal 35-J shocks delivered by an implanted cardioverter defibrillator (ICD). He had suffered from acute inferior myocardial infarction 6 years earlier, complicated with sustained polymorphic ventricular tachycardia (VT). Due to inducibility of sustained VT on an electrophysiologic study, an ICD was implanted. Defibrillation testing performed after healing of anteroseptal infarction was successful with a 10-J safety margin, suggesting that acute myocardial ischemia transiently elevated the internal defibrillation threshold.

Novel Electrode Design for Potentially Painless Internal Defibrillation Also Allows for Successful External Defibrillation

Implantable cardioverter defibrillators (ICDs) save lives, but the defibrillation shocks delivered by these devices produce substantial pain, presumably due to skeletal muscle activation. In this study, we tested an electrode system composed of epicardial panels designed to shield skeletal muscles from internal defibrillation, but allow penetration of an external electric field to enable external defibrillation when required. Eleven adult mongrel dogs were studied under general anesthesia. Internal defibrillation threshold (DFT) and shock-induced skeletal muscle force at various biphasic shock strengths were compared between two electrode configurations: (1) a transvenous coil placed in the right ventricle (RV) as cathode and a dummy can placed subcutaneously in the left infraclavicular fossa as anode (control configuration) and (2) RV coil as cathode and the multielectrode epicardial sock with the panels connected together as anode (sock-connected). External DFT was also tested with these electrode configurations, as well as with the epicardial sock present, but with panels disconnected from each other (sock-disconnected). Internal DFT was higher with sock-connected than control (24 +/- 7 J vs. 16 +/- 6 J, P < 0.02), but muscle contraction force at DFT was greatly reduced (1.3 +/- 1.3 kg vs. 10.6 +/- 2.2 kg, P < 0.0001). External defibrillation was never successful, even at 360 J, with sock-connected, while always possible with sock-disconnected. Internal defibrillation with greatly reduced skeletal muscle stimulation can be achieved using a novel electrode system that also preserves the ability to externally defibrillate when required. This system may provide a means for painless ICD therapy.

Effects of Angiotensin Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker on Ventricular Defibrillation Threshold

Angiotensin converting enzyme (ACE) inhibitors and Angiotensin II (AII) receptor blockers have previously been shown to be beneficial in treating patients with not only hypertension but also with cardiovascular diseases. Therefore, such drugs may potentially be used in patients with an implantable cardioverter defibrillator (ICD) who show cardiac dysfunctions. This study aimed to determine effects of short-term administration of the ACE inhibitor (CV-3317) and the AII receptor blocker (CV-11974, an active form of candesartan) on internal defibrillation threshold (DFT) in anesthetized canine hearts. DFTs were evaluated using a "hot can" defibrillation lead system in: (a) seven dogs following three intravenous administrations of 20 cc saline; (b) 11 dogs that received intravenous CV-3317 doses of 1 mg/kg, 10 mg/kg, and 50 mg/kg; and in (c) 10 dogs that were intravenously given 0.1 mg/kg, 1 mg/kg, and 10 mg/kg CV-11974. DFTs were determined using a "down-up down-up" protocol. Mean DFT delivered energies at baseline and following three consecutive intravenous saline injections were 16.4 +/- 9.3 J, 15.3 +/- 7.5 J, 15.9 +/- 7.1 J, and 15.5 +/- 5.6 J, respectively. Those at baseline and following 1 mg/kg, 10 mg/kg, and 50 mg/kg intravenous CV-3317 were 12.9 +/- 6.4 J, 12.2 +/- 6.4 J, 11.0 +/- 6.6 J, and 11.9 +/- 6.6 J, respectively. Similarly, those at baseline and after 0.1 mg/kg, 1 mg/kg, and 10 mg/kg CV-11974 were 13 +/- 6.6 J, 12.5 +/- 6 J, 12.9 +/- 5.8 J, and 13.2 +/- 6.6 J, respectively. There were no significant differences between DFT at baseline and the others in each treatment group. Since an ACE inhibitor and an AII receptor blocker did not alter DFT, such drugs may be useful in ICD patients without a decrease in safety margins.

Internal defibrillation with minimal skeletal muscle activation: A new paradigm toward painless defibrillation

Shock-induced pain produces substantial morbidity in recipients of implantable cardioverter-defibrillators (ICDs). This pain likely derives from activation of skeletal muscle and associated nerves in the chest and abdomen. In an effort to develop a painless defibrillation system, we designed an electrode arrangement that incorporates a conductive sock placed around the heart to confine the electric shock field to cardiac tissue. The purpose of this study was to test whether cardiac defibrillation could be achieved without skeletal muscle activation using a novel electrode system. Eight adult mongrel dogs were studied. Force of skeletal muscle contraction was measured by strain gauges attached to the forelimbs during delivery of internal shocks ranging in energy from 0.1 to 31 J. Biphasic shocks were delivered (1) between a right ventricular coil and a subcutaneous dummy can (standard configuration), and (2) between a left ventricular coil and an epicardial electrode sock. Internal and external defibrillation thresholds (DFTs) were determined for each electrode configuration. Shock-induced muscle contraction force was significantly lower using the sock electrode than with standard ICD electrodes at every shock energy level tested (P < .0001). Internal DFT was similar between electrode configurations (sock electrode: 8.6 +/- 4.2 J; standard: 11.0 +/- 6.3 J, P = .4), but muscle contraction force at DFT was greatly reduced with the new electrode system (1.8 +/- 2.0 kg vs 10.6 +/- 2.1 kg, P < .0001). The sock electrode rendered external defibrillation impossible, however, even at 360 J. Skeletal muscle activation induced by ICD shocks can be greatly reduced using an electrode system that confines the electric shock field to the heart. Refinement of this strategy may allow for delivery of painless shocks by ICDs. Further development is needed to overcome implant complexity and the higher external DFT with this type of electrode system.

Effect of isoproterenol on facilitation of electrical defibrillation by E-4031.

To determine whether isoproterenol could reverse enhancement of electrical defibrillation effectiveness by class III antiarrhythmic agents, we measured the internal defibrillation threshold (DFT) in 12 anesthetized dogs during infusion of (a) saline (baseline), (b) isoproterenol, (c) isoproterenol + E4031 (a new class III antiarrhythmic agent), and (d) E4031 alone. The isoproterenol infusion was adjusted so that heart rate (HR) was at least 30 beats/min greater than baseline. E4031 was given as a 40-micrograms/kg bolus at the beginning of the third stage of the study, followed by constant infusion at 2 micrograms/kg/min. Eight dogs completed the study. Although the energy-based DFT was not affected by isoproterenol (from 6.1 +/- 1.5 to 6.0 +/- 1.7 J), it was decreased to 3.7 +/- 1.6 J in the third stage by infusion of E4031 and isoproterenol (p < 0.01 vs. baseline and vs. isoproterenol). After the discontinuation of isoproterenol in the fourth stage, i.e., during infusion of E4031 alone, DFT was 3.4 +/- 1.6 J (p < 0.01 vs. baseline and vs. isoproterenol). Therefore, isoproterenol did not antagonize the effect of E4031 on the DFT, suggesting the possible clinical usefulness of class III agents for facilitating defibrillation even in the presence of augmented sympathetic activity.

Shock-induced refractory period extension and pharmacologic modulation of defibrillation threshold.

Shock-induced refractory period extension (RPE) has been suggested as a mechanism of electrical defibrillation. We measured RPE caused by localized field stimulation measured before and during infusion of disopyramide (n = 5), flecainide (n = 5), or E-4031 (n = 5) in anesthetized dogs and determined the effect of the drugs on the internal defibrillation threshold (DFT). In the baseline state (n = 15), 16 V/cm S2 field stimulation prolonged the effective RP by 36 +/- 15 ms (22 +/- 12% of RP without S2), whereas 4 and 8 V/cm S2 stimuli did not cause marked RPE. The RPE normalized by the RP without S2 was not significantly influenced by any drug (16 V/cm: disopyramide 30 +/- 11 vs. 27 +/- 11, flecainide 25 +/- 5 vs. 19 +/- 12, and E-4031 18 +/- 13 vs. 22 +/- 14%). Disopyramide did not alter the defibrillation threshold (4.2 +/- 0.6-4.4 +/- 0.6 J). In 2 dogs given flecainide, ventricular fibrillation became refractory to defibrillation. In contrast, E-4031 lowered the threshold from 4.5 +/- 2.4 to 2.2 +/- 1.2 J (p < 0.01). The results suggest that flecainide and E-4031 do not modulate defibrillation efficiency through their effects on RPE.

Effective Defibrillation in Pigs Using Interleaved and Common Phase Sequential Biphasic Shocks

Previous studies have shown that low internal defibrillation thresholds (DFTs) can be attained by using two pairs of electrodes and combining biphasic shocks with sequential timing. The purpose of this two-part study was to test the defibrillation efficacy of two new shock sequences, an interleaved biphasic, and a common phase sequential biphasic, that utilized two pairs of electrodes and were developed from the concept of sequential biphasic shocks. In the first part, defibrillation catheters were placed in the right ventricle and the superior vena cava of six anesthetized pigs. A small patch electrode was placed on the LV apex through a subxiphoid incision and a cutaneous patch was placed on the left thorax. The mean DFT energies for the interleaved biphasic (5.2 +/- 0.4 J) and the common phase sequential biphasic waveforms (5.4 +/- 0.4 J) were substantially less (P < 0.0001) than those for either the sequential monophasic (10.6 +/- 1.0 J) or single biphasic waveforms (9.0 +/- 1.0 J). In the second study, which used nine anesthetized pigs, the importance of phase reversal was demonstrated by the finding that the DFT energy of a common phase sequential biphasic shock (6.2 +/- 0.4 J) was much less than a common phase sequential monophasic shock (17.9 +/- 1.3 J, P < 0.0001); furthermore, the average DFT for four common phase sequential biphasic configurations (5.7 +/- 0.2 J) was much less than for a configuration that was similar except that current flow was not reversed in one phase so that no biphasic effect was present (19.7 +/- 1.2 J). The efficacy of common phase sequential biphasics was comparable to that of sequential biphasics. The effectiveness of sequential biphasics, interleaved biphasics, and common phase sequential biphasics is possibly due to two mechanisms: (A) an increase in the potential gradient during a later phase in regions that were low during the first phase, and (B) the exposure of most of the myocardium to a biphasic shock that reduces the minimum extracellular potential gradient needed to defibrillate.

Effects of acute and prolonged administration of propafenone on internal defibrillation in the pig

Some antiarrhythmic sodium channel blocking drugs have been found to increase the energy necessary for internal defibrillation. Propafenone is a new drug that has been shown to be efficacious in the therapy of supraventricular and ventricular arrhythmias, and is of potential use in patients with defibrillators. The effects of short-term and prolonged propafenone administration on the internal defibrillation threshold (DFT) were determined in 43 pigs randomized to one of four groups: saline infusion ( n = 10); propafenone infusion ( n = 10); placebo administration for 8 days ( n = 10); or propafenone administration for 8 days ( n = 13). Two mesh electrodes were sutured on the right lateral and left lateral epicardial surface and current was delivered from the right electrode to the left electrode. Triplicate DFTs were obtained before and at 40 and 80 minutes after infusion of drug or placebo. In pigs receiving long-term administration, after baseline DFTs were obtained the electrodes were removed and the chest was closed. Following 8 days of drug or placebo administration, DFTs were redetermined. No changes were observed in the short- or long-term control groups. DFTs were lower after propafenone administration; either short-term infusion (20 ± 6.2 joules at baseline; 15.6 ± 5 joules at 40 minutes, p < 0.05; 10.2 ± 6 joules at 80 minutes, p < 0.001) or long-term administration (17.8 ± 2.6 joules at baseline versus 12 ± 3.2 joules on drug, p < 0.002). Decreased ventricular cycle lengths were found with acute administration of propafenone. Three pigs died during long-term administration of propafenone. In this model, with propafenone administration a significant improvement in defibrillation efficacy was observed that could be of clinical importance if verified in patients.

Ethanol increases internal defibrillation threshold in pigs

Ethanol increases internal defibrillation threshold in pigs

Comparison of the internal defibrillation thresholds for monophasic and double and single capacitor biphasic waveforms

Implantable cardiac defibrillators are now an accepted form of therapy for patients with life-threatening ventricular arrhythmias that cannot be controlled by antiarrhythmic drugs. These devices could be made even more acceptable if they were smaller, had increased longevity and the surgical procedure for implantation was less invasive. Reducing the energy requirements for internal defibrillation with use of a nonthoracotomy lead system would make all of these goals achievable.Monophasic and double and single capacitor biphasic waveforms were compared in 14 anesthetized dogs (25.5 ± 2.2 kg) with use of a nonthoracotomy lead system that has previously been shown to distribute the delivered voltage throughout the heart more equally. Cathodal catheter electrodes were placed in the right ventricular apex and outflow tract. The anodal electrode was a large cutaneous R2 patch placed over the left side of the chest. The mean energy requirement for defibrillation when a single capacitor biphasic waveform was used was significantly less (6.4 ± 2.6 J) than that for either the double capacitor biphasic or the monophasic waveform (18.0 ± 8.0 and 17.4 ± 8.0 J, respectively) of the same duration. Unexpectedly, the leading edge voltage for the phase I of the single capacitor biphasic waveform was significantly less (266 ± 51 V) than that for either the double capacitor biphasic or the monophasic waveform (336 ± 76 and 427 ± 117 V, respectively). In conclusion, in large dogs, defibrillation is possible at low energy levels with a single capacitor biphasic waveform.