Oscar H. Tovar

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.

Electrophysiology of ventricular fibrillation and defibrillation

The survival rate from ventricular fibrillation is very high for short-duration fibrillation (<30 secs) but decreases to approximately 3% to 30% in out-of-hospital conditions. During short-duration fibrillation, action potentials occur rapidly with no intervening period of electrical diastole; a shock defibrillates by interacting with the fibrillation action potential to produce a uniformly long postshock extension of refractoriness. In contrast, during long-duration fibrillation, ischemia-induced degradation of cellular electrophysiology occurs, which causes intervening periods of electrical diastole between fibrillation action potentials and, thus, slowing of fibrillation frequency. A successful defibrillation shock must now not only prolong refractoriness when delivered during the action potential but must also excite cells during the periods of depolarized diastole. Biphasic waveforms enhance both effects by causing premature membrane repolarization with the first pulse, thereby allowing sodium channel recovery from inactivation so that the second pulse produces better-formed responses both during the cellular action potential and during the depolarized diastole. Therefore, biphasic waveforms remain superior to monophasic waveforms for treatment of long-duration fibrillation. Improved understanding of the ischemia-induced changes in cellular electrophysiology will suggest further improvements in both defibrillator waveforms and resuscitation techniques.

Can shocks timed to action potentials in low-gradient regions improve both internal and out-of-hospital defibrillation?☆

Abstract During the first minute of fibrillation, circulating wavefronts excite new fibrillation action potentials almost immediately following termination of the preceding action potential. The extension of refractoriness hypothesis states that a successful defibrillating shock must produce a uniform postshock refractoriness of a specific optimal duration throughout the ventricle, which blocks these wavefronts and terminates fibrillation. We hypothesized that, if shocks are appropriately timed early in the fibrillation action potential in low-voltage-gradient regions, postshock refractoriness will already be long and the shock need not be strong enough to further extend it. This will result in a lower defibrillation threshold (DFT). This hypothesis was tested in the isolated rabbit heart model. Shocks were synchronized to monophasic action potentials recorded from a low-intensity region. An up/down protocol was used. I 50 for early shocks was 17% lower than that for late shocks (31% decrease in E 50 ). Standard deviation of I 50 was reduced from 32% for late shocks to 18% for early shocks. Therefore, shock synchronization improves both DFT and inter-subject variability during early fibrillation. As fibrillation duration increases, action potential frequency decreases and periods of diastole occur. Because of these ischemic changes, it is uncertain whether shock timing can produce similar improvements in defibrillation under out-of-hospital conditions.

Diastolic intervals accompany increased cycle length following two minutes fibrillation

Following short fibrillation durations, fibrillation action potentials occur immediately upon repolarization from the previous action potential. However, Fourier analysis shows that frequency of fibrillation decreases with fibrillation duration and that the decrease is correlated with the difficulty of defibrillation. We tested the hypothesis that the decrease in fibrillation frequency is accompanied by the appearance of diastolic intervals between fibrillation action potentials. Fibrillation was induced in isolated rabbit hearts (n=5) and perfusate immediately clamped to make the hearts ischemic. ECGs and monophasic action potentials (MAPs) were recorded. Cycle length increased from 81.8/spl plusmn/6.5 following 5 seconds fibrillation to 111.6/spl plusmn/5.9 msec following 1.5 minutes fibrillation (p<0.004). Action potential duration (APD90) was 73.5/spl plusmn/8.3 msec at two minutes. The period of diastolic resting potential was 42.8/spl plusmn/6.7 msec. Our results suggest that the mechanism underlying fibrillation changes as fibrillation duration increases due to the developing ischemia.

Interaction of tilt and stimulus intensity on prolongation of refractory period with monophasic and biphasic defibrillating waveforms

Waveform shape and stimulus intensity are both critical in determining efficacy of defibrillating waveforms. To test the hypothesis that clinically reIevant biphasic waveforms reduce defibrillation threshold by reducing postshock dispersion of refractoriness, we examined action potential duration prolongation induced by 8 msec total duration monophasic and biphasic waveforms with 0, 42, and 65% tilt at stimulus intensities of 15 and 5 times S1 threshold. The results show that biphasic waveforms cause less difference in total response duration dispersion as stimulus intensity increases than do monophasic waveforms. These results suggest that, while long duration biphasic waveforms reduce defibrillation threshold by enhancing refractoriness at low intensities, short duration, asymmetrical, clinical waveforms reduce dispersion by preventing action potential prolongation in high intensity regions of the heart. Because dispersion of refractoriness induces refibrillation, preventing dispersion increases defibrillation efficacy.

Epicardial potential gradients induced by defibrillation shocks to hearts immersed and non-immersed in a conducting solution

Studies of defibrillation threshold (DFT) or local epicardial potential gradients (LPG) are performed in open chest preparations or in isolated hearts immersed in solution (I) or exposed to air [non-immersed (NI)]. However, DFT depends on LPG in the low intensity region. In this study the authors determined differences in LPG produced by I and NI. Monophasic shocks (n=123) from a voltage-controlled defibrillator were delivered to 4 perfused rabbit hearts through epicardial patch electrodes either NI or I in Krebs solution interleaved in random order. Shock intensities (SI) ranged from 40-160 V. LPG were determined using two, perpendicular pairs of bipolar electrodes placed in a low LPG region (bipole spacing=5 mm). Impedance was significantly higher in NI than in I hearts (99.9/spl plusmn/1.5 vs 76.5/spl plusmn/1.33 /spl Omega/, p<0.0001), the NI/I ratio was 0.76. LPG differed as a function of SI and were higher in NI (n=57 episodes) than in I hearts (n=66) (p<0.00001), the NI/I ratio was 0.67. These results show that changes in cardiac volume conductor alter LPG distribution and local epicardial SI. These differences can produce significant variation in DFT and measured potential gradients; they must be considered in interpreting defibrillation studies.

Effect of epinephrine on frequency content of ventricular fibrillation and probability of spontaneous defibrillation

Epinephrine stabilizes ventricular fibrillation (VF) in the isolated perfused rabbit heart. We tested the hypothesis that epinephrine allows sustained fibrillation by increasing the rate and dispersion of its frequency content. VF was induced in sixteen isolated rabbit hearts, under control conditions and in the presence of epinephrine (100 /spl mu/g/L). The probability of spontaneous defibrillation was determined in 8 hearts (155 episodes). The frequency content of VP was determined in a separate group of 8 hearts using fast Fourier transform of epicardial monophasic action potential (MAP) recordings (23 episodes). The probability of spontaneous defibrillation was 29% under control conditions and 8% with epinephrine (p<0.05). The mean dominant frequency of fibrillation was 10.0/spl plusmn/0.2 Hz with a narrow bandwidth under control conditions and 14.1/spl plusmn/0.2 Hz with a wider bandwidth after epinephrine, p<0.0001. These results suggest that, in isolated rabbit hearts, epinephrine increases the mean rate and dispersion of fibrillation leading to its stabilization.

Immediate termination of fibrillation at 50% probability of overall success correlates with defibrillation dose-response curve width.

Introduction: Issues in transthoracic defibrillation, including waveform shape, fixed versus escalating dose protocol, and low‐ versus high‐energy shocks, can be addressed by examining the defibrillation dose‐response curve. We tested the hypothesis that, for commonly used defibrillation waveforms, the steepness of the overall defibrillation dose‐response curve, measured as normalized curve width, correlates with the probability of a successful defibrillation being immediate at the shock intensity producing 50% success.

Recovery of ventricular pressure after long-duration fibrillation/asystole

When ventricular fibrillation occurs out-of-hospital, fewer than 3% of patients survive to hospital discharge. Following long fibrillation durations associated with out-of-hospital fibrillation, asystole or electromechanical dissociation (EMD) frequently follows the defibrillating shock. When this happens, recovery of spontaneous circulation rarely occurs. Therefore, this study tested the hypothesis that ventricular recovery from asystole or EMD is possible if the heart is subsequently perfused at normal pressures with O/sub 2/ saturated solution. Isolated rabbit hearts (n=5) were subjected to 9 minutes ischemic fibrillation followed by a defibrillating shock. All hearts converted to asystole or EMD. At 23 seconds following the shock, the hearts were reperfused with oxygenated solution. Ventricular pressure recovered 57.2/spl plusmn/11.9% of control at 36.0/spl plusmn/1.9 seconds and 76.2/spl plusmn/11.8% at 5 minutes. These results suggest that rapid pressure recovery is possible after 9 minutes of ischemic fibrillation where the defibrillating shock leads to asystole or EMD, and that recovery can occur in the absence of epinephrine or CPR prior to the shock.