Janice L. Jones

Conditioning prepulse of biphasic defibrillator waveforms enhances refractoriness to fibrillation wavefronts.

The mechanism of biphasic waveform defibrillation threshold reduction is unknown. We tested the hypothesis that, during refractory period stimulation, sarcolemmal hyperpolarization by the first pulse of biphasic waveforms facilitates excitation channel recovery, which enhances graded responses produced by the second depolarizing pulse. This prolongs cellular refractoriness to fibrillation wavefronts when compared with a monophasic depolarizing stimulus. Monophasic (10 msec, rectangular wave) or symmetrical biphasic (10 msec, each pulse) current injection S2 stimuli at 1.5 and two times S1 threshold were used to scan the S1 action potential refractory period (S1 cycle length, 600 msec) in myocardial cell aggregates. S2 waveforms were delivered with normal and reversed polarity to test the hyperpolarizing action of biphasic waveforms. Responses to an S3 stimulus, which simulated a potential incoming fibrillation wavefront, were also determined. Results showed that biphasic S2 waveforms produced longer graded responses during and immediately after the S1 refractory period than did corresponding monophasic S2 waveforms. The maximum difference in response duration produced by the biphasic and monophasic waveforms was 58.6 +/- 10.0 msec (p less than 0.001). This maximum difference occurred 10 msec before the end of the S1 refractory period. The longer response durations produced by biphasic S2 also produced longer refractoriness to the S3 stimulus. The maximum difference in total refractoriness to S3 of 51.8 +/- 2.8 msec (p less than 0.002) occurred at the same S1S2 coupling interval as the maximum difference in S2 response duration. Prolonged refractoriness may protect ventricular cells from refibrillation wavefronts and act as the cellular basis for greater biphasic waveform defibrillation efficacy.

Increasing fibrillation duration enhances relative asymmetrical biphasic versus monophasic defibrillator waveform efficacy.

Biphasic waveforms reduce defibrillation threshold compared with corresponding monophasic waveforms. However, effects of fibrillation duration on relative efficacy of monophasic and biphasic waveforms are unknown. This study used a newly developed defibrillation model, the isolated right- and left-sided working rabbit heart, with epicardial defibrillation electrodes, to compare threshold for a monophasic waveform (5 msec rectangular) and an asymmetrical biphasic waveform (5 msec each pulse, V2 = 50% V1). Mean voltage defibrillation threshold (V50) was determined from sigmoidal probability of successful defibrillation versus shock intensity curves after 5, 15, and 30 seconds of fibrillation in a paired study with 10 hearts. Results showed that biphasic waveforms had significantly lower voltage and energy thresholds at all fibrillation durations and that their relative efficacy improved with increasing fibrillation duration. Biphasic voltage threshold was 38.2 +/- 2.2, 44.7 +/- 4.8, and 46.6 +/- 3.2 V after 5, 15, and 30 seconds of fibrillation compared with monophasic thresholds of 51.7 +/- 4.4 (p less than 0.002), 63.0 +/- 7.6 (p less than 0.05), and 72.1 +/- 3.9 V (p less than 0.005). Biphasic waveform energy threshold was 0.67 that for the monophasic waveform after 5 seconds of fibrillation (0.12 +/- 0.01 versus 0.18 +/- 0.03 J, p less than 0.05). The ratio between biphasic waveform threshold and monophasic waveform threshold (B/M) decreased to 0.62 at 15 seconds. At 30 seconds, B/M was 0.52 (0.17 +/- 0.02 versus 0.33 +/- 0.04 J, p less than 0.02). This study also showed that biphasic waveform threshold was a nonlinear function of monophasic waveform threshold so that improved biphasic defibrillator waveform efficacy was greatest for hearts having higher monophasic thresholds.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Refractory period prolongation by biphasic defibrillator waveforms is associated with enhanced sodium current in a computer model of the ventricular action potential

Mechanisms through which biphasic waveforms lower defibrillation threshold are unknown. Previous work showed that low-intensity biphasic shocks (BS2), delivered during the refractory period of a control action potential (S1), produced significantly longer responses than monophasic shocks (MS2). To test the hypothesis that longer responses are due to hyperpolarization-induced excitation channel recovery during the first portion of the biphasic waveform, the authors used the Beeler-Reuter ventricular action potential computer model with the Drouhard-Roberge (BRDR) modification to study refractory period stimulation with MS2 (10 msec) and symmetrical BS2 (10 msec each pulse). At 1.5 times diastolic threshold, BS2 prolonged action potential duration when delivered 50 msec into the S1 refractory period, and produced a maximum BS2 versus MS2 response duration difference of 62 msec. Longer BS2 responses corresponded to enhanced BS2-induced sodium current compared to MS2. Maximum BS2 vs MS2 sodium current difference was 400 uA/cm/sup 2/. These results show that, in a computer model of the ventricular action potential, hyperpolarization by the first phase of a biphasic waveform enhances S2 sodium current and prolongs duration of refractory-period responses. This effectively shortens the cellular refractory period. Prolonged refractory period responses, produced by biphasic defibrillator waveforms, may underlie enhanced defibrillating efficacy at low shock intensities.<<ETX>>

Relative Efficacy of Monophasic and Biphasic Waveforms for Transthoracic Defibrillation After Short and Long Durations of Ventricular Fibrillation

BACKGROUND Recently, interest has arisen in using biphasic waveforms for external defibrillation. Little work has been done, however, in measuring transthoracic defibrillation efficacy after long periods of ventricular fibrillation. In protocol 1, we compared the efficacy of a quasi-sinusoidal biphasic waveform (QSBW), a truncated exponential biphasic waveform (TEBW), and a critically damped sinusoidal monophasic waveform (CDSMW) after 15 seconds of fibrillation. In protocol 2, we compared the efficacy of the more efficacious biphasic waveform from protocol 1, QSBW, with CDSMW after 15 seconds and 5 minutes of fibrillation. METHODS AND RESULTS In protocol 1, 50% success levels, ED50, were measured after 15 seconds of fibrillation for the 3 waveforms in 6 dogs. In protocol 2, defibrillation thresholds were measured for QSBW and CDSMW after 15 seconds of fibrillation and after 3 minutes of unsupported fibrillation followed by 2 minutes of fibrillation with femoral-femoral cross-circulation. In protocol 1, QSBW had a lower ED50, 16.0+/-4.9 J, than TEBW, 20.3+/-4.4 J, or CDSMW, 27.4+/-6.0 J. In protocol 2, QSBW had a lower defibrillation threshold after 15 seconds, 38+/-10 J, and after 5 minutes, 41.5+/-5 J, than CDSMW after 15 seconds, 54+/-19 J, and 5 minutes, 80+/-30 J, of fibrillation. The defibrillation threshold remained statistically the same for QSBW for the 2 fibrillation durations but rose significantly for CDSMW. CONCLUSIONS In this animal model of sudden death and resuscitation, these 2 biphasic waveforms are more efficacious than the CDSMW at short durations of fibrillation. Furthermore, the QSBW is even more efficacious than the CDSMW at longer durations of fibrillation.

Calcium dynamics in cultured heart cells exposed to defibrillator-type electric shocks.

Spatial and temporal changes in intracellular calcium ion concentration and transmembrane voltage were recorded optically from single-isolated cultured chick-embryo heart cells exposed to high-voltage, defibrillator-type shocks. Fluorescence changes were measured during 5 msec electric shocks of field strengths up to 56 volts/cm in single myocytes stained with a Ca(++)-sensitive or voltage-sensitive dye. Shocks caused a reversible period of depolarization, elevated cytosolic Ca++, and refractoriness. Intracellular Ca++ elevation had two temporal phases: first, a Ca++ spike with morphology independent of shock intensity; and second, a prolonged Ca++ elevation with a shock-intensity-dependent magnitude and duration, and with greatest Ca++ elevation at the poles of the cell adjacent to the electrodes. The prolonged elevation (second phase) was initiated earlier at the anode-facing pole of the cell than at the cathode-facing pole. These results suggest that postshock Ca++ entry consists of two parts: early normal entry through excitation channels plus a prolonged elevation which may be related to cellular damage.

Biphasic Defibrillation Waveforms Reduce Shock-Induced Response Duration Dispersion Between Low and High Shock Intensities

Mechanisms underlying defibrillation threshold reduction with biphasic waveforms remain unclear. The interaction of local shock-induced voltage gradients, which change with distance from the shocking electrode, and the state of membrane repolarization results in different cellular responses that may influence the success of defibrillation. We used intracellular microelectrodes and S1S2 pacing protocols in myocardial cell aggregates to determine the effects of shock intensity and waveform on refractory period responses during simulated fibrillation (3 s of S1 pacing at 180-ms cycle length). We simulated defibrillation by electric field stimulation S2 using 8-ms monophasic (MS2) and 4/4 biphasic (BS2) waveforms (65% total tilt) delivered at intensities of 1.5, 3, and 5 times S1 diastolic threshold, or approximately 2 to 7 V/cm. Responses following MS2 varied with S2 intensity and coupling interval (P < .001). When averaged over the last 10 ms of the refractory period, MS2 produced a negligible response (8.8 +/- 1.4 ms) at 1.5 times diastolic threshold and a prolonged response (53.0 +/- 3.1 ms) at 5 times diastolic threshold (P < .01). In contrast, BS2 response duration did not change significantly (P - NS) between 1.5 times diastolic threshold (35.1 +/- 12.6 ms) and 5 times diastolic threshold (46.2 +/- 2.7 ms). Our results suggest that biphasic waveforms not only prolong response duration at low shock intensity but reduce dispersion of refractoriness produced by differing local potential gradients generated by defibrillation shocks compared with monophasic waveforms. Preventing dispersion of refractoriness and prolonging shock-induced responses may improve biphasic waveform efficacy at low shock intensity.

Electrophysiological deterioration during long-duration ventricular fibrillation.

BackgroundProbability of survival from sudden cardiac arrest caused by ventricular fibrillation (VF) decreases rapidly with fibrillation duration. We hypothesized that cellular ischemia/fibrillation-induced electrophysiological deterioration underlies decreased survival. Methods and ResultsWe determined fibrillation monophasic action potential (MAP) morphology including action potential frequency content, duration, cycle length, developing diastolic intervals, and amplitude as a function of ischemic fibrillation duration in 10 isolated rabbit hearts. We also correlated ECG frequency (used clinically) and MAP amplitude and frequency. Fibrillation cycle length and diastole duration increased, whereas APD100 shortened significantly with time (P <0.001). Between 1 and 3 minutes, diastole appeared primarily as the result of APD100 shortening, with only small changes in cycle length. Between 2 and 5 minutes, diastole increased primarily as the result of increased cycle length. Diastole developed progressively from 5% of VF cycles at 5 seconds to ≈100% of VF cycles by 120 seconds (P <0.001). Diastole increased from 1% of cycle length at 5 seconds to 62% at 5 minutes. Its duration increased from 4.7 ms at 5 seconds to 90 ms at 5 minutes (P <0.001). Both MAP and ECG 1/frequency closely correlated with fibrillation cycle length. ConclusionsThese results show a rapid and progressive electrophysiological deterioration during fibrillation, leading to electrical diastole between fibrillation action potentials. This rapid deterioration may explain the decreased probability of successful resuscitation after prolonged fibrillation. Therefore, a greater understanding of cellular deterioration during fibrillation may lead to improved resuscitation methods, including development of specific defibrillator waveforms for out-of-hospital cardiac arrest.

Effect of Shock Timing on Defibrillation Success

The goal of this study was to determine whether delivering transvenous defibrillation shocks, coordinated with the up/down‐slope VF waveform patterns in the shocking lead, would improve the probability of successful defibrillation. Anesthetized swine (32–38 kg, n = 8) were implanted with an RV → SVC + SQArray transvenous system to measure VF waveform patterns and to deliver shocks. The shocks were generated by a Cardiac Pacemakers Inc. biphasic waveform generator. Energy required for 50% success probability (E50) was determined using the multishock up‐down protocol. VF was repeatedly induced and defibrillation shocks at E50 were given after 10 seconds. The defibrillation outcome, delivered energy (Ed), peak voltage (V), peak current (I), system impedance (Z) and VF waveform pattern at the time of shock were recorded and measured. Out of a total of 685 shocks, 324 (47%) succeeded and 361 (53%) failed. The Ed, V, I, and Z were similar for the two defibrillation outcome groups (success or failure). VF patterns were classified as high or low amplitude at the time of the shock based on the peak‐to‐peak amplitude of signals recorded between shocking electrodes. Shocks that coincided with high amplitude VF patterns were further divided into shocks that occurred on the up‐slope or on the down‐slope. The probability of success when the E50 shocks were coincident with high or low amplitude fibrillation did not differ significantly (Students t‐test: 46% vs 48%, P = NS). However, during high amplitude fibrillation, shocks delivered on the up‐slope were significantly more successful than those delivered on the down‐slope (Chi‐square: 67% vs 39%; P < 0.001). These results suggest that delivering defibrillation shocks during the up‐slope of the high amplitude signal in the shocking lead may improve the probability of successful defibrillation of ICDs.

Triphasic waveforms are superior to biphasic waveforms for transthoracic defibrillation: experimental studies.

OBJECTIVES Our objective was to evaluate the efficacy of triphasic waveforms for transthoracic defibrillation in a swine model. BACKGROUND Triphasic shocks have been found to cause less post-shock dysfunction than biphasic shocks in chick embryo studies. METHODS After 30 s of electrically induced ventricular fibrillation (VF), each pig in part I (n = 32) received truncated exponential biphasic (7.2/7.2 ms) and triphasic (4.8/4.8/4.8 ms) transthoracic shocks. Each pig in part II (n = 14) received biphasic (5/5 ms) and triphasic shocks (5/5/5 ms). Three selected energy levels (50, 100, and 150 J) were tested for parts I and II. Pigs in part III (n = 13) received biphasic (5/5 ms) and triphasic (5/5/5 ms) shocks at a higher energy (200 and 300 J). Although the individual pulse durations of these shocks were equal, the energy of each pulse varied. Nine pigs in part I also received shocks where each individual pulse contained equal energy but was of a different duration (biphasic 3.3/11.1 ms; triphasic 2.0/3.2/9.2 ms). RESULTS Triphasic shocks of equal duration pulses achieved higher success than biphasic shocks at delivered low energies: <40 J: 38 +/- 5% triphasic vs. 19 +/- 4% biphasic (p < 0.01); 40 to <50 J: 66 +/- 7% vs. 42 +/- 7% (p < 0.01); and 50 to <65 J: 78 +/- 4% vs. 54 +/- 5% (p < 0.05). Shocks of equal energy but different duration pulses achieved relatively poor success for both triphasic and biphasic waveforms. Shock-induced ventricular tachycardia (VT) and asystole occurred less often after triphasic shocks. CONCLUSIONS Triphasic transthoracic shocks composed of equal duration pulses were superior to biphasic shocks for VF termination at low energies and caused less VT and asystole.