Postshock Arrhythmias Research Articles

Abstract 363: Dantrolene Decreases Susceptibility to Refibrillations by Restoring Vf Dependent Cardiac Calcium Handling Dysfunction

Background: Ventricular refibrillation frequently occurs after successful defibrillation of Ventricular Fibrillation (VF) and negatively affects outcomes. Diastolic elevation in cytosolic calcium and dysfunction in calcium handling is proposed to underlie post-shock arrhythmias. Ryanodine Receptor 2 (RyR2) is the major calcium handling protein in cardiomyocytes. its dysfunction causes diastolic calcium leak from sarcoplasmic reticulum and calcium transient amplitude alternans (Ca-Alt), which can lead to arrhythmias. We hypothesized Dantrolene protects against refibrillations by restoring cardiac calcium handling and stabilizing RyR2 after VF. Methods and Results: Hearts from 14 healthy New-Zealand rabbits were excised and perfused using Langendorff method; VF(+ISO) was induced by burst pacing and left untreated for 4 min. Hearts received either Dantrolene (20μM) or saline during VF. Upon defibrillation, 4 more VF episodes were attempted. Sustainability (VF≥60 sec) and inducibility of refibrillations (VF≥10 sec) was evaluated. Calcium mapping using RhoD-2 was performed to assess Ca-Alt and diastolic Spontaneous Calcium Elevation (SCaE). Ca-Alt was defined as ≥10% variability in Calcium transient amplitudes. SCaE amplitude was measured during diastolic pause after termination of pacing. In total, 83.33% of attempts to induce refibrillation in controls were successful compared to 41.18% in Dantrolene-treated hearts. (P=0.007) Dantrolene (20μM) significantly decreased SCaE amplitude post VF. (Table 1) Ca-Alt emerged at shorter PCL in Dantrolene-treated hearts with 10% decrease from 195±9.5ms at baseline to 173±6.7ms post-VF compared to 11% increase in controls from 215±20ms to 235±8ms. (P=0.05) Conclusion: Dantrolene ameliorated arrhythmogenic diastolic SCaE caused by VF and increased calcium alternans threshold and may be the basis for the decreased susceptibility of treated hearts to refibrillations.

Dantrolene Decreases Susceptibility to Refibrillations by Restoring VF-Dependent Cardiac Calcium Handling Dysfunction

Ventricular refibrillation frequently occurs after successful defibrillation of Ventricular Fibrillation (VF) and negatively affects the outcomes. Sustained elevation in cytosolic calcium and dysfunction in intracellular calcium handling has been proposed to underlie post-shock arrhythmias in rabbit hearts. Ryanodine Receptor 2 (RyR2) is the major calcium handling protein in cardiomyocytes and its dysfunction causes diastolic calcium leak from sarcoplasmic reticulum and calcium transient amplitude alternans (Ca-Alt), which can result in arrhythmias. We hypothesized that Dantrolene protects against refibrillations by restoring cardiac calcium handling and stabilizing RyR2 after VF.

High-energy defibrillation increases the dispersion of regional ventricular repolarization

This study evaluated the effects of shock energy on the dispersion of regional ventricular repolarization (DRVR), post-shock rhythm and sinus recovery time (SRT), and the relationship between DRVR and post-shock ventricular arrhythmias. Ten open-chest dogs were anesthetized. Ventricular fibrillation (VF) was electrically induced and recorded from a 6 × 6 unipolar electrode plaque (4 mm spacing) sutured on the left ventricular epicardium. Defibrillation threshold (DFT) was determined after 20 s of VF. DRVR was measured before VF, during the earliest post-shock sinus rhythm, and during sinus rhythm 30 s following shocks. Post-shock rhythm and SRT were evaluated after energies of 100% DFT, 125% DFT, 175% DFT, and 250% DFT. In the100% DFT group, the DRVR of the earliest sinus rhythm and 30 s after successful defibrillation was not significantly different than that before VF. But the DRVRs were significantly increased in 125% DFT, 175% DFT, and 250% DFT group. DRVR after defibrillation in the 250% DFT group was higher than those in the 100% DFT and 125% DFT groups. SRT in the 250% DFT group was significantly longer than that in the other groups .The incidence of post-shock ventricular tachycardia was increased when a high-shock energy was applied (P = 0.041). DRVR was increased by application of high-energy defibrillation associated with SRT prolongation. The increased DRVR may play an important role in the onset of post-shock ventricular tachycardia.

Importance of Intracellular Calcium-Membrane Voltage Coupling Gain in Post-Shock Ventricular Arrhythmias

Objective: Ventricular tachycardia/fibrillation (VT/VF) can recur repeatedly after defibrillation (i.e. electrical storm). We tested the hypothesis that intracellular Ca2+ (Cai) overload during VF and sensitivity of membrane voltage (Vm) to Cai (Cai-Vm coupling gain) is important for post-shock arrhythmias. Methods and Results: We simultaneously mapped Cai and Vm on epicardial (n=14) or endocardial (n=14) surfaces of Langendorff-perfused rabbit ventricles. Spontaneous Cai elevation (SCaE) was noted after defibrillation in 32% of VT/VF at baseline, 83% during isoproterenol infusion. SCaE was reproducibly induced by rapid ventricular pacing and inhibited by ryanodine. We found triggered activities (TAs) originating from 6 of 14 endocardial surfaces but none from epicardial surfaces, despite similar SCaEs between epicardial and endocardial surfaces. This was because delayed afterdepolarizations induced by SCaEs were larger on endocardial surfaces due to higher Cai-Vm coupling gain. Purkinje-like potentials preceded the TAs. /K1 suppression with CsCl or BaCl2 enhanced Cai-Vm coupling gain and enabled epicardium to also generate TAs. Further enhancement of Cai overload and Cai-Vm coupling gain by low [K+]o induced post-shock VTs and spontaneous VF recurrences leading to electrical storm. Conclusions: Cai-Vm coupling gain is important for the genesis of post-shock VT/VF and electrical storm. Purkinje fibers serve as arrhythmogenic substrate because of its higher Cai-Vm coupling gain. /K1 is a major determinant for Cai-Vm coupling gain.

Arrhythmogenic Foci and the Mechanisms of Atrial Fibrillation

In this issue of the Circulation: Arrhythmia and Electrophysiology , Kurotobi et al1 determined the number of arrhythmogenic foci in atria provocable with isoproterenol infusion in patients with paroxysmal, persistent, and permanent atrial fibrillation (AF). The results show that persistent AF has more foci than paroxysmal AF. However, when AF persists for >12 months, the number of foci were reduced. The authors suggest that the increased number of foci probably is involved in the development of persistent AF. However, because this association is not observed for AF that persists for >12 months, the importance of these foci in AF maintenance remains unclear. Article see p 39 In ambulatory canine models, simultaneous sympathovagal discharges (rather than isolated sympathetic activation) are typical triggers of paroxysmal atrial tachycardia (AT) and AF.2,3⇓ These observations are explained by the late phase-3 early afterdepolarization (EAD), which depends on the coexistence of increased amplitude and duration of intracellular calcium (Cai) transient and the shortened action potential duration (APD).4,5⇓ Vagal stimulation shortens APD and therefore is needed to promote the late phase-3 EAD. In the Kurotobi study, however, arrhythmogenic foci were induced by isoproterenol alone, without the need of vagal stimulation or the use of parasympathomimetic agents. These results are different from that obtained in canine studies. The first possible explanation is that the pulmonary veins (PVs) naturally have shorter APDs with elevated (less negative) membrane potentials.6,7⇓ Rapid activation may further shorten the APD in the PVs.8 These changes are independent of the vagal tone. Jais et al9 reported the effective refractory periods of the PVs were shorter …

Diastolic Intracellular Calcium-Membrane Voltage Coupling Gain and Postshock Arrhythmias

Recurrent ventricular arrhythmias after initial successful defibrillation are associated with poor clinical outcome. We tested the hypothesis that postshock arrhythmias occur because of spontaneous sarcoplasmic reticulum Ca release, delayed afterdepolarization (DAD), and triggered activity (TA) from tissues with high sensitivity of resting membrane voltage (V(m)) to elevated intracellular calcium (Ca(i)) (high diastolic Ca(i)-voltage coupling gains). We simultaneously mapped Ca(i) and V(m) on epicardial (n=14) or endocardial (n=14) surfaces of Langendorff-perfused rabbit ventricles. Spontaneous Ca(i) elevation (SCaE) was noted after defibrillation in 32% of ventricular tachycardia/ventricular fibrillation at baseline and in 81% during isoproterenol infusion (0.01 to 1 micromol/L). SCaE was reproducibly induced by rapid ventricular pacing and inhibited by 3 mumol/L of ryanodine. The SCaE amplitude and slope increased with increasing pacing rate, duration, and dose of isoproterenol. We found TAs originating from 6 of 14 endocardial surfaces but none from epicardial surfaces, despite similar amplitudes and slopes of SCaEs between epicardial and endocardial surfaces. This was because DADs were larger on endocardial surfaces as a result of higher diastolic Ca(i)-voltage coupling gain, compared to those of epicardial surfaces. Purkinje-like potentials preceded TAs in all hearts studied (n=7). I(K1) suppression with CsCl (5 mmol/L, n=3), BaCl(2) (3 micromol/L, n=3), and low extracellular potassium (1 mmol/L, n=2) enhanced diastolic Ca(i)-voltage coupling gain and enabled epicardium to also generate TAs. Higher diastolic Ca(i)-voltage coupling gain is essential for genesis of TAs and may underlie postshock arrhythmias arising from Purkinje fibers. I(K)(1) is a major factor that determines the diastolic Ca(i)-voltage coupling gain.

Differences between left and right ventricular anatomy determine the types of reentrant circuits induced by an external electric shock. A rabbit heart simulation study

Despite the fact that elucidating the mechanisms of cardiac vulnerability to electric shocks is crucial to understanding why defibrillation shocks fail, important aspects of cardiac vulnerability remain unknown. This research utilizes a novel anatomically based bidomain finite-element model of the rabbit ventricles to investigate the effect of shock polarity reversal on the reentrant activity induced by an external defibrillation-strength shock in the paced ventricles. The specific goal of the study is to examine how differences between left and right ventricular chamber anatomy result in differences in the types of reentrant circuits established by the shock. Truncated exponential monophasic shocks of duration 8 ms were delivered via two external electrodes at various timings. Vulnerability grids were constructed for shocks of reversed polarity (referred to as RV− or LV− when either the RV or the LV electrode is a cathode). Our results demonstrate that reversing electrode polarity from RV− to LV− changes the dominant type of post-shock reentry: it is figure-of-eight for RV− and quatrefoil for LV− shocks. Differences in secondary types of post-shock arrhythmia also occur following shock polarity reversal. These effects of polarity reversal are primarily due to the fact that the LV wall is thicker than the RV, resulting in a post-shock excitable gap that is predominantly within the LV wall for RV− shocks and in the septum for LV− shocks.

Shock-induced arrhythmogenesis in the myocardium.

The focus of this article is the investigation of the electrical behavior of the normal myocardium following the delivery of high-strength defibrillation shocks. To achieve its goal, the study employs a complex three-dimensional defibrillation model of a slice of the canine heart characterized with realistic geometry and fiber architecture. Defibrillation shocks of various strengths and electrode configurations are delivered to the model preparation in which a sustained ventricular tachycardia is induced. Instead of analyzing the post-shock electrical events as progressions of transmembrane potential maps, the study examines the evolution of the postshock phase singularities (PSs) which represent the organizing centers of reentry. The simulation results demonstrate that the shock induces numerous PSs the majority of which vanish before the reentrant wavefronts associated with them complete half of a single rotation. Failed shocks are characterized with one or more PSs that survive the initial period of PS annihilation to establish a new postshock arrhythmia. The increase in shock strength results in an overall decrease of the number of PSs that survive over 200 ms after the end of the shock; however, the exact behavior of the PSs is strongly dependent on the shock electrode configuration. (c) 2002 American Institute of Physics.

Optical mapping of arrhythmias induced by strong electrical shocks in myocyte cultures.

Strong electrical shocks can induce arrhythmias, which might explain why shocks fail to defibrillate. In this work, the localization of arrhythmia source and the relationship with local changes of transmembrane potential (V(m)) were determined in geometrically defined cell cultures using optical mapping technique. Uniform-field shocks with strength (E) of 10 to 50 V/cm were applied across cell strands with width of 0.2 and 0.8 mm. The threshold for arrhythmia induction was dependent on the strand width: in the 0.8- and 0.2-mm strands, arrhythmias were induced at E>/=20.6+/-1.8 V/cm (n=8) and E>/=30.3+/-1.8 V/cm (n=8), respectively. At the same shock strength, the arrhythmia rate and duration were larger in the wider strands. During shocks that induced arrhythmias, the V(m) waveforms on the anodal side revealed a positive V(m) shift that followed the initial large hyperpolarization and postshock elevation of the diastolic V(m). These V(m) changes were absent during failed shocks. To determine the localization of the arrhythmia source, arrhythmias were induced in narrow cell strands containing regions of local expansion. Optical mapping of the first extrabeat with a coupling interval of 315+/-60 ms revealed that in the majority of cases (9 out of 13) the source of arrhythmias was localized in the areas of shock-induced hyperpolarization. Thus, (1) induction of postshock arrhythmias, their rate, and their duration strongly depend on the tissue structure; (2) arrhythmia induction coincides with the appearance of a positive V(m) shift in the areas of hyperpolarization; and (3) the source of postshock arrhythmias is located in the areas of shock-induced hyperpolarization.

Energy levels for defibrillation: what is of real clinical importance?

Today, transthoracic and intracardiac defibrillation offer a well-accepted and widely used form of therapy for patients with life-threatening ventricular arrhythmias. Despite the wide clinical use of defibrillators, the mechanisms by which an electrical shock halts fibrillation are still not completely understood. During a shock, different amounts of current flow through the different parts of the heart and the current distribution is highly uneven. This current distribution is affected by changes in the shock potential gradient through the heart, changes in fiber orientation, and changes in myocardial conductivity caused by connective tissue barriers. It would be ideal if the potential gradient distribution throughout the ventricles could be measured directly for each individual patient during defibrillator implantation and follow-up and the shock strength could be programmed based on this measurement, but so far this is not possible. A more feasible approach is to determine, by trial and error, the magnitude of the shock strength delivered through the defibrillation electrodes for successful defibrillation. There is no distinct threshold value above which all shocks succeed and below which all shocks fail to defibrillate. Rather, increasing shock strength increases the likelihood the shock will succeed. Therefore, instead of a distinct defibrillation threshold, a probability of success curve exists. However, increasing the shock strength above an optimal range can actually decrease the success rate for defibrillation. One possible explanation is that the high voltage gradients caused by such large shocks damage cells and result in postshock arrhythmias that may reinitiate fibrillation. Another problem that can affect the probability of defibrillation success for a particular programmed energy setting is that the shock strength required for defibrillation may increase over time due to (1) the growth of fibrotic tissue around the defibrillation electrode; (2) migration of the lead; (3) acute ischemia; or (4) other changes in the underlying cardiac disease (e.g., worsening of heart failure). Such possible increases in the defibrillation shock strength requirement should be compensated for before they occur by adding a margin of safety to the shock strength needed for effective defibrillation. When programming an implantable defibrillator, it is important to keep in mind that the defibrillation shock should be (1) strong enough to defibrillate at least 98% of the time with the first shock; (2) weak enough not to cause severe postshock arrhythmias or reinitiation of fibrillation; but (3) strong enough to compensate for changes of defibrillation energy requirements over time. This usually can be accomplished by setting the defibrillator 7–10 J higher than the defibrillation threshold determined by a standard step-down protocol.

Adequacy of implantable cardioverter-defibrillator lead placement for tachyarrhythmia detection by sinus rhythm electrogram amplitude

This study examines whether the current clinical practice of using a 5 mV minimum amplitude during normal sinus rhythm (NSR) ensures adequate detection during subsequent episodes of ventricular fibrillation (VF) at the time of the implantable cardioverter-defibrillator (ICD) threshold testing. Risk of nondetection occurs with ICDs when a substantial portion of the individual cardiac events on an electrogram goes undetected. Detection risk was assessed by 2 methods: percentage of missed cardiac events (incidence of signal dropout), and mean electrogram amplitude. During ICD implantation and testing in 27 patients utilizing 41 lead positions, 135 episodes of VF were induced and analyzed. On 64 occasions, the countershock was not successful in achieving cardioversion, and the continuing electrical activity was analyzed as a separate group of postshock waveforms. Thresholds of 1 and 2 mV were applied to each individual cardiac depolarization in a VF episode. Significant risk of nondetection was assumed when ≥10% of individual events displayed dropout. Underdetection by signal dropout occurred in 11 of 135 preshock arrhythmia signals (8.1%) from 3 patients at a 2 mV threshold, and in 6 of 135 signals (4.4%) at a 1 mV threshold. A mean NSR amplitude ≥5 mV was associated with significantly lower risk of nondetection during subsequent VF episodes at both 1 and 2 mV thresholds (largest p < 0.001). Similar results were observed in analysis of postshock arrhythmia signals. Further examination of signal dropout and linear regression criteria suggest that in order to eliminate the possibility of nondetection at a 1 mV threshold, minimum NSR amplitudes of 8.5 and 10.0 mV, respectively, are required.

The Probability of Defibrillation Success and the Incidence of Postshock Arrhythmia as a Function of Shock Strength

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

Defibrillation shocks produce different effects on purkinje fibers and ventricular muscle: Implications for successful defibrillation, refibrillation and postshock arrhythmia

Objectives. To understand the mechanisms of postdefibrillation arrhythmias and failed defibrillation, we studied the cellular effects of high voltage shocks on different cardiomyocytes in the dog.Background. The causes of postdefibrillation arrhythmias and unsuccessful defibrillation are not clear.Methods. High voltage shocks with voltage differentials of 9.3 to 97.6 V/cm were delivered to isolated canine papillary muscles with attached Purkinje fibers. Transmembrane potentials were recorded simultaneously from the Purkinje fiber and the ventricular muscle using standard microelectrode techniques.Results. After delivery of high voltage shocks, significant depolarization and rapid firing were observed in Purkinje fibers. The maximal rate of the rapid firing in the Purkinje fibers correlated with shock intensity (r = 0.69, p < 0.05). In contrast, in ventricular muscle, only slight depolarization and a transient refractory state were observed after the shock. The incidence of the refractory state was correlated with both the shock intensity and the rate of the rapid firing in the Purkinje fiber (r = 0.89 and 0.74, p < 0.01 and 0.05, respectively). Propranolol at a concentration sufficient for complete beta-blockade (1 mg/liter) did not change the tissue response to shocks but suppressed or abolished the shock-induced rapid firing of Purkinje fibers at a higher concentration (3 mg/liter). Blockade of the slow calcium channel with verapamil (400 μg/dl) did not alter the responsiveness of the preparation to shocks.Conclusion. These results indicate that high voltage shocks induce different responses in Purkinje fibers and ventricular muscle. The shock-induced rapid firing in the Purkinje fiber may contribute to postshock arrhythmias and possibly refibrillation in some cases. The shock-induced transient refractory state in the ventricular muscle may prevent the ventricle from responding to the rapid firing and thus may decrease the incidence of postshock arrhythmias.

Dysrhythmias after direct-current cardioversion

The success rate of direct-current (DC) counter-shocks 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 VG 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 < 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 post-shock 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.

Decreased defibrillator-induced dysfunction with biphasic rectangular waveforms.

High-intensity electric shocks used for cardiac defibrillation produce arrhythmias, S-T segment changes, and a low percent success in situ. Cultured myocardial cells exhibit similar postshock arrhythmias that are caused by a prolonged depolarization of the cell membrane. Since this dysfunction is ameliorated by biphasic RLC-type waveforms, we examined rectangular biphasic waveforms to maximize this beneficial effect and clarify the dysfunction-inducing mechanism. Cultured myocardial cells were subjected to electric field stimulation with monophasic 5-ms rectangular waveforms of about 80 V/cm to produce a postshock arrest of contractile activity lasting 4 s. Shocks given with this control waveform were alternated with biphasic test waveforms having the same initial portion followed by negative "tails" 1-100 ms in duration and 5-100% of the initial positive portion in amplitude. Results from 31 biphasic waveforms demonstrated significant alterations in postshock dysfunction. Waveforms with up to 10% undershoot and ranging from 5 to 100 ms in duration decreased arrest time by up to 50%; waveforms with greater than 20% undershoot led to protracted postshock arrest times. These results strengthen the hypothesis that electromechanical breakdown of the myocardial cell membrane underlies postshock dysfunction and show that biphasic waveforms with low amplitude tails ameliorate this dysfunction.

Improved defibrillator waveform safety factor with biphasic waveforms.

Excitation thresholds and arrhythmias were studied in "adult-type" cultured chick embryo myocardial cells after electric field stimulation with biphasic, truncated, and rectified underdamped RLC (resistance-inductance-capacitance) type waveforms, to test the hypothesis that the negative phase of biphasic waveforms ameliorates membrane dysfunction induced by the initial positive portion. Photocell mechanograms and intracellular microelectrodes monitored extrasystoles and depolarization-induced arrhythmias. Rectifying or truncating biphasic waveforms did not alter the excitation threshold. However, shock intensities producing specific postshock arrhythmias or a specific severity of postshock prolonged depolarization differed significantly when biphasic waveforms were truncated or rectified. The voltage gradient producing a specific dysfunction was 12-14% lower for the truncated version than for the biphasic; that for the rectified version was 17-27% lower than for the biphasic version (although both contained the same energy). Safety factor, the ratio between shock intensity producing specific dysfunction and that producing excitation, was determined for each waveform. Biphasic waveforms had larger safety factors than truncated or rectified waveforms. Since safety factor, as measured in cultured myocardial cells, closely corresponds with in situ defibrillating effectiveness (14), the significantly higher safety factors of biphasic waveforms suggest that carefully shaped biphasic waveforms might improve the efficacy and safety of cardiac defibrillation procedures.

Alterations induced by a single defibrillating shock applied through a chronically implanted catheter electrode

In ten beagles ranging in weight from 7.4 to 13.0 kg, a defibrillating shock of 10 A (three dogs), 20 A (four dogs), or 30 A (three dogs) intensity was applied through a chronically implanted right ventricular catheter electrode. Ten-lead ECG, right ventricular electrogram, and right ventricular impedance were recorded prior to, immediately following, and 48 hours post-shock. A single shock of 10 A, 20 A, and 30 A intensity succeeded in defibrillating nine of ten dogs. One dog required two 20 A shocks to defibrillate. No shock was fatal. Post-shock arrhythmias increased in duration and severity as the shock strength increased. ECG vector analysis suggested damage to the right ventricle in eight of ten dogs. The impedance signal amplitude increased directly after the shock, but dropped below control level by 200 seconds post-shock and remained below control by 48 hours post-shock. Pale areas of shock-induced myocardial necrosis were concentrated in the right ventricular walls adjacent to the distal electrode. The mean weight of necrotic myocardium was 0.043 + 0.006 grams at 10 A, 1.203 + 0.268 grams at 20 A, and 1.397 + 1.218 grams at 30 A (mean + sd). Defibrillation was effective after long-term implantation. The alterations sustained from defibrillation were minimized by using a low intensity shock.

Determination of safety factor for defibrillator waveforms in cultured heart cells.

We studied excitation thresholds and arrhythmias produced in cultured chick embryo myocardial cells subjected to electric shocks using rectangular, untruncated resistor-capacitor (RC), and critically damped resistor-inductor-capacitor (RLC) waveforms with variable intensities while photocell mechanograms were recorded. Strength-duration curves for excitation and production of a specific postshock arrhythmia (4-s arrest) were constructed. Excitation curves closely resembled those for in situ defibrillation threshold (or specific % success). The ratio between the shock intensity producing a 4-s arrest and that producing excitation at each duration (termed the "safety factor") was determined. Waveforms with a large safety factor in vitro defibrillated most effectively in situ with little postshock dysfunction. Waveforms with low safety factors had a low rate of success in situ and produced much postshock dysfunction. Safety factor of monophasic clinical waveforms were lower than that of the 5-ms rectangular wave. The close correspondence between in vitro safety factor and in situ defibrillating effectiveness, as reported in the literature, suggests that the cell culture system is an effective screening system for determining waveforms that will improve the efficacy and safety of defibrillation procedures.

Cardiac damage caused by direct application of defibrillator shocks to isolated Langendorffperfused rabbit heart

The purpose of this study was to establish the damaging dose of defibrillator pulses. The damage caused to isolated perfused rabbit hearts by synchronized defibrillator shocks with a stored energy from 15 up to 70 joules is reported. The damage was characterized by the duration and severity of post-shock arrhythmias, changes in the elastic properties of the left ventricle, the first derivative of left ventricular pressure, morphological changes of the heart muscle, elevation of creatine kinase, potassium washout, and a change in mean coronary flow rate. Varying the electrode area showed that densities of applied current and energy are major factors in damaging the heart. At current and energy densities of 0.5 amp./cm. 2 and 0.6 J./cm. 2, respectively, potassium washout and mild arrhythmias are seen, as is complete arrest of the ventricles at 1.2 amp./cm. 2 and 1.5 J./cm. 2 pulses. After 1.8 amp./cm. 2, irreversible cell damage occurs, as demonstrated by CK release, and also cardiac function is reduced, measured by increased diastolic stiffness and decreased contractility. Current and energy densities exceeding 2.5 amp./cm. 2 and 4.2 J./cm. 2, respectively, cause changes in cardiac function incompatible with life. Accumulation of damage was observed with a series of 1.2 amp./cm. 2 shocks.

Postshock arrhythmias--a possible cause of unsuccessful defibrillation.

Clinical and experimental information exists in the literature which suggests that defibrillation with higher energies than are required results in a decreased percentage of success. Previous work in this laboratory which showed the occurrence of postshock arrhythmias caused by a prolonged depolarization of the cell membrane in myocardial cells in vitro, led to the hypothesis that the decreased percent success at high energies in vivo might be due to the development of similar shock-induced arrhythmias which could immediately refibrillate the heart. The purpose of these experiments was to test this hypothesis. Myocardial cells grown in vitro were subjected to rectangular wave electric field stimulation of varying intensity and duration. Postshock arrhythmias were evaluated using a photovoltaic cell mounted on a closed-circuit television monitor. The photocell converted the change in light intensity produced as the cell contracted to an electrical signal which was read out on a strip chart. Strength-duration curves were formed both for excitation (production of a single extrasystole) and for specific degrees of arrhythmia. These were compared with strength-duration curves obtained for a specific percent success defibrillation in vivo by other investigators. These experiments showed a close similarity between the in vivo and in vitro data, thus, strengthening the hypothesis that decreasing percentage of success of defibrillation with increasing intensity at high energies is due to secondary arrhythmias produced by the shock. The experiments further suggest that in vitro myocardial cells are a valuable screening system for determining waveforms which maximize the ratio between the voltages producing postshock arrhythmias and those producing excitation (defibrillation). This ratio, defined as the "safety factor" of the waveform, varies with the duration of the rectangular wave. Durations having high safety factors can produce defibrillation with a high percentage of success; however, waveforms having low safety factors make it impossible to achieve a high percentage of success defibrillation with any applied voltage. This information suggests that the minimum voltage required for successful defibrillation always be used and that defibrillators be produced with waveforms which maximize the safety factor.