Epicardial wavefronts arise from widely distributed transient sources during ventricular fibrillation in the isolated swine heart.

It has been proposed that VF waves emanate from stable localized sources, often called "mother rotors." However, evidence for the existence of these rotors is conflicting. Using a new panoramic optical mapping system that can image nearly the entire ventricular epicardium, we recently excluded epicardial mother rotors as the drivers of Wiggers' stage II VF in the isolated swine heart. Furthermore, we were unable to find evidence that VF requires sustained intramural sources. The present study was designed to test the following hypotheses: 1. VF is driven by a specific region, and 2. Rotors that are long-lived, though not necessarily permanent, are the primary generators of VF wavefronts. Using panoramic optical mapping, we mapped VF wavefronts from 6 isolated swine hearts. Wavefronts were tracked to characterize their activation pathways and to locate their originating sources. We found that the wavefronts that participate in epicardial reentry were not confined to a compact region; rather they activated the entire epicardial surface. New wavefronts feeding into the epicardial activation pattern were generated over the majority of the epicardium and almost all of them were associated with rotors or repetitive breakthrough patterns that lasted for less than 2 s. These findings indicate that epicardial wavefronts in this model are generated by many transitory epicardial sources distributed over the entire surface of the heart.

Stimulus-induced critical point. Mechanism for electrical initiation of reentry in normal canine myocardium.

The hypothesis was tested that the field of a premature (S2) stimulus, interacting with relatively refractory tissue, can create unidirectional block and reentry in the absence of nonuniform dispersion of recovery. Simultaneous recordings from a small region of normal right ventricular (RV) myocardium were made from 117 to 120 transmural or epicardial electrodes in 14 dogs. S1 pacing from a row of electrodes on one side of the mapped area generated parallel activation isochrones followed by uniform parallel isorecovery lines. Cathodal S2 shocks of 25 to 250 V lasting 3 ms were delivered from a mesh electrode along one side of the mapped area to scan the recovery period, creating isogradient electric field lines perpendicular to the isorecovery lines. Circus reentry was created following S2 stimulation; initial conduction was distant from the S2 site and spread towards more refractory tissue. Reentry was clockwise for right S1 (near the septum) with top S2 (near the pulmonary valve) and for left S1 with bottom S2; and counterclockwise for right S1 with bottom S2 and left S1 with top S2. The center of the reentrant circuit for all S2 voltages and coupling intervals occurred at potential gradients of 5.1 +/- 0.6 V/cm (mean +/- standard deviation) and at preshock intervals 1 +/- 3 ms longer than refractory periods determined locally for a 2 mA stimulus. Thus, when S2 field strengths and tissue refractoriness are uniformally dispersed at an angle to each other, circus reentry occurs around a "critical point" where an S2 field of approximately 5 V/cm intersects tissue approximately at the end of its refractory period.

Activation during ventricular defibrillation in open-chest dogs. Evidence of complete cessation and regeneration of ventricular fibrillation after unsuccessful shocks.

To test the hypothesis that a defibrillation shock is unsuccessful because it fails to annihilate activation fronts within a critical mass of myocardium, we recorded epicardial and transmural activation in 11 open-chest dogs during electrically induced ventricular fibrillation (VF). Shocks of 1-30 J were delivered through defibrillation electrodes on the left ventricular apex and right atrium. Simultaneous recordings were made from septal, intramural, and epicardial electrodes in various combinations. Immediately after all 104 unsuccessful and 116 successful defibrillation shocks, an isoelectric interval much longer than that observed during preshock VF occurred. During this time no epicardial, septal, or intramural activations were observed. This isoelectric window averaged 64 +/- 22 ms after unsuccessful defibrillation and 339 +/- 292 ms after successful defibrillation (P less than 0.02). After the isoelectric window of unsuccessful shocks, earliest activation was recorded from the base of the ventricles, which was the area farthest from the apical defibrillation electrode. Activation was synchronized for one or two cycles following unsuccessful shocks, after which VF regenerated. Thus, after both successful and unsuccessful defibrillation with epicardial shocks of greater than or equal to 1 J, an isoelectric window occurs during which no activation fronts are present; the postshock isoelectric window is shorter for unsuccessful than for successful defibrillation; unsuccessful shocks transiently synchronize activation before fibrillation regenerates; activation leading to the regeneration of VF after the isoelectric window for unsuccessful shocks originates in areas away from the defibrillation electrodes. The isoelectric window does not support the hypothesis that defibrillation fails solely because activation fronts are not halted within a critical mass of myocardium. Rather, unsuccessful epicardial shocks of greater than or equal to 1 J halt all activation fronts after which VF regenerates.

Nonlinear changes of transmembrane potential during defibrillation shocks: role of Ca(2+) current.

Defibrillation shocks induce complex nonlinear changes of transmembrane potential (DeltaV(m)). To elucidate the ionic mechanisms of nonlinear DeltaV(m), we studied the effects of ionic channel blockers on DeltaV(m) in geometrically defined myocyte cultures. Experiments were carried out in cell strands with widths of 0.2 mm (narrow strands) and 0.8 mm (wide strands) produced using a technique of directed cell growth. Uniform-field shocks were applied across strands during the action potential (AP) plateau, and the distribution of shock-induced DeltaV(m) was measured using an optical mapping technique. Nifedipine and 4-aminopyridine were applied to inhibit the L-type calcium current (I:(Ca)) and the transient outward current (I:(to)), respectively. In control conditions, the distribution of DeltaV(m) across cell strands was highly asymmetrical with a large ratio of negative to positive DeltaV(m) (DeltaV(-)(m)/DeltaV(+)(m)) measured at the opposite strand borders. Application of nifedipine caused a large increase of DeltaV(+)(m) and a decrease of DeltaV(-)(m)/DeltaV(+)(m), indicating involvement of I:(Ca) in the asymmetrical DeltaV(m), likely as a result of the outward flow of I:(Ca) when V(m) exceeded the I:(Ca) reversal potential. DeltaV(-)(m) decreased in the narrow strands but remained unchanged in the wide strands, indicating that the changes of DeltaV(-)(m) were caused by electrotonic interaction with an area of depolarization. 4-Aminopyridine did not change DeltaV(-)(m)/DeltaV(+)(m). These results provide evidence that (1) the asymmetry of shock-induced DeltaV(m) during the AP plateau is due to outward flow of I:(Ca) in the depolarized portions of the strands, (2) I:(to) is not involved in the mechanism of DeltaV(m) asymmetry, and (3) the effects of drugs on DeltaV(m) are modulated by the tissue geometry.

Shock-induced figure-of-eight reentry in the isolated rabbit heart.

The patterns of transmembrane potential on the whole heart during and immediately after fibrillation-inducing shocks are unknown. To study arrhythmia induction, we recorded transmembrane activity from the anterior and posterior epicardial surface of the isolated rabbit heart simultaneously using 2 charge-coupled device cameras (32,512 pixels, 480 frames/second). Isolated hearts were paced from the apex at a cycle length of 250 ms. Two shock coils positioned inside the right ventricle (-) and atop the left atrium (+) delivered shocks at 3 strengths (0.75, 1.5, and 2.25 A) and 6 coupling intervals (130 to 230 ms). The patterns of depolarization and repolarization were similar, as is evident in the uniformity of action potential duration at 75% repolarization (131.4¿8.3 ms). At short coupling intervals (<180 ms), shocks hyperpolarized a large portion of the ventricles and produced a pair of counterrotating waves, one on each side of the heart. The first beat after the shock was reentrant in 90% of short coupling interval episodes. At long coupling intervals (>180 ms), increasingly stronger shocks depolarized an increasingly larger portion of the heart. The first beat after the shock was reentrant in 18% of long coupling interval episodes. Arrhythmias were most often induced at short coupling intervals (98%) than at long coupling intervals (35%). The effect and outcome of the shock were related to the refractory state of the heart at the time of the shock. Hyperpolarization occurred at short coupling intervals, whereas depolarization occurred at long coupling intervals. Consistent with the "critical point" hypothesis, increasing shock strength and coupling interval moved the location where reentry formed (away from the shock electrode and pacing electrode, respectively).

Influence of postshock epicardial activation patterns on initiation of ventricular fibrillation by upper limit of vulnerability shocks.

BACKGROUND: Shocks of identical strength and timing sometimes induce ventricular fibrillation (VFI) and other times do not (NoVFI). To investigate this probabilistic behavior, a shock strength near the upper limit of vulnerability, ULV(50), was delivered to yield equal numbers of VFI and NoVFI episodes. METHODS AND RESULTS: In 6 pigs, a 504-electrode sock was pulled over the ventricles. ULV(50) was determined by scanning the T wave. S(1) pacing was from the right ventricular apex. Ten S(2) shocks of approximate ULV(50) strength were delivered at the same S(1)-S(2) coupling interval. Intercycle interval (ICI) and wave front conduction time (WCT) were determined for the first 5 postshock cycles. ICI and the WCT of cycle 1 were not different for VFI versus NoVFI episodes (P=0.3). Beginning at cycle 2, ICI was shorter and WCT was longer for VFI than NoVFI episodes (P<0.05). CONCLUSIONS: The first cycle after shocks of the same strength (ULV(50)) delivered at the same time has the same activation pattern regardless of shock outcome. During successive cycles, however, a progressive decrease in ICI and increase in WCT occur during VFI but not NoVFI episodes. These findings suggest shock outcome is (1) deterministic but exquisitely sensitive to differences in electrophysiological state at the time of the shock that are too small to detect or (2) probabilistic and not determined until after the first postshock cycle.

Left ventricular apex ablation decreases the upper limit of vulnerability.

BACKGROUND: After shocks with an approximately 50% probability of success for the upper limit of vulnerability (ULV(50)) of strength, the first few activations appear focally on the epicardium at almost the same site at the left ventricular (LV) apex in both successful and failed induction of ventricular fibrillation (VF). We tested the hypothesis that subendocardial ablation at this early site would decrease the shock strength required for the ULV(50). METHODS AND RESULTS: Ten S1 stimuli were delivered from the right ventricular apex at a 300-ms coupling interval in 5 pigs. Biphasic shocks were delivered from right ventricular-superior vena cava electrodes after the last S1 stimulus. The ULV(50) was determined using an up/down protocol with T-wave scanning. Radiofrequency ablation was performed endocardially at the apical LV. The ULV(50) was determined again 30 minutes after ablation. To determine the importance of the ablation region, this protocol was repeated in another 5 pigs with ablation at the LV base. Delivered voltage (401+/-60 versus 323+/-50 V) and energy (11+/-3 versus 7+/-2 J) for the ULV(50) were significantly decreased after LV apex ablation by 19% and 34%, respectively. However, no difference existed in ULV(50) before and after LV base ablation. Lesions at both the LV apex and base were subendocardial and ranged from 0.8 to 1.1 cm in diameter. CONCLUSIONS: Subendocardial ablation at the apical LV markedly decreases ULV(50), which suggests that the activation originating from this postshock early site is responsible for VF initiation and that interventions to electrically silence this site can influence the outcome of VF induction by ULV shocks.

Mechanism of ventricular defibrillation for near-defibrillation threshold shocks: a whole-heart optical mapping study in swine.

BACKGROUND: To study the mechanism by which shocks succeed (SDF) or fail (FDF) to defibrillate, global cardiac activation and recovery and their relationship to defibrillation outcome were investigated for shock strengths with approximately equal SDF and FDF outcomes (DFT(50)). METHODS AND RESULTS: In 6 isolated pig hearts, dual-camera video imaging was used to record optically from approximately 8000 sites on the anterior and posterior ventricular surfaces before and after 10 DFT(50) biphasic shocks. The interval between the shock and the last ventricular fibrillation activation preceding the shock (coupling interval, CI) and the time from shock onset to 90% repolarization of the immediate postshock action potential (RT(90)) were determined at all sites. Of 60 shocks, 31 were SDF. The CI (59+/-7 versus 52+/-6 ms) and RT(90) (108+/-19 versus 88+/-8 ms) were significantly longer for SDF than FDF episodes. Spatial dispersions of CI (36+/-5 versus 34+/-3 ms) and RT(90) (40+/-16 versus 40+/-8 ms) were not significantly different for SDF versus FDF episodes. The first global activation cycle appeared focally on the left ventricular apical epicardium 78+/-32 ms after the shock. CONCLUSIONS: For near-threshold shocks, defibrillation outcome correlates with the electrical state of the heart at the time of the shock and on RT. Global dispersion of RT was similar in both SDF and FDF episodes, suggesting that it is not crucial in determining defibrillation outcome after DFT(50) shocks.

Right atrial septal electrode for reducing the atrial defibrillation threshold.

BACKGROUND: The atrial defibrillation threshold (ADFT) energy of the standard lead configuration, right atrial appendage (RAA) to coronary sinus (CS), was reduced by >50% with the addition of a third electrode traversing the atrial septum in a previous study. This study determined whether the ADFT would be lowered by a more clinically practical third electrode placed in the right atrium along the atrial septum (RSP). METHODS AND RESULTS: Sustained atrial fibrillation was induced in 8 closed-chest sheep with burst pacing and maintained with pericardial infusion of acetyl-beta-methylcholine chloride. A custom-made, dual-defibrillation catheter was placed with electrodes in the lateral RA, CS, and RSP. A separate defibrillation catheter was also placed in the RAA. ADFT characteristics of RAA-->CS and 6 other single- or sequential-shock configurations were determined in random order by using biphasic, truncated-exponential waveforms in a multiple-reversal protocol. The delivered-energy, peak-voltage, and peak-current ADFTs for the sequential-shock configuration CS-->RSP/RA-->RSP (0.53+/-0.31 J, 86+/-22 V, and 1.6+/-0.6 A, respectively) were significantly lower than those of RAA-->CS (1.14+/-0.64 J, 157+/-34 V, and 2.5+/-1.1 A, respectively). The ADFT characteristics of RAA-->CS and RA-->CS were not significantly different, nor were those of CS-->RSP/RA-->RSP and CS-->RSP/RAA--> RSP. CONCLUSIONS: The ADFT of the standard RAA-->CS configuration may be markedly reduced with an additional electrode situated at the RSP.

Prevention of high incidence of neurally mediated ventricular arrhythmias by afferent nerve stimulation in dogs.

BACKGROUND: This study tested the hypothesis that the high incidence of ventricular arrhythmias caused by hypothalamic stimulation during acute myocardial ischemia could be attenuated by afferent nerve stimulation and investigated the cardiac mechanisms for those effects. METHODS AND RESULTS: In 18 anesthetized dogs, stimulating electrodes were implanted in the hypothalamus and in the isolated left peroneal nerve. The chest was opened and approximately 100 plunge needles were inserted into the ventricles for 3-D activation mapping. Each animal underwent 4 episodes of 2.5 minutes of acute myocardial ischemia. The first and fourth episodes served as controls. During the second and third episodes, animals received either hypothalamic stimulation, peroneal nerve stimulation, or both. Hypothalamic stimulation significantly increased the incidence of ventricular arrhythmias. This high incidence was reduced 34% by simultaneous stimulation of the hypothalamus and peroneal nerve. 3-D mapping showed a focal origin for all ventricular arrhythmias. Hypothalamic stimulation increased the number of arrhythmic beats and decreased the coupling interval between each arrhythmic beat and the preceding beat. These effects were reduced by peroneal nerve stimulation. CONCLUSIONS: Alteration in autonomic tone by hypothalamic stimulation causes a high incidence of ventricular arrhythmias during acute myocardial ischemia that can be decreased by afferent nerve stimulation.

Ventricular defibrillation with triphasic waveforms.

BACKGROUND: It has been reported that triphasic defibrillation waveforms cause less myocardial injury than biphasic waveforms. This study compared the defibrillation thresholds (DFTs) of triphasic and biphasic waveforms. METHODS AND RESULTS: ++DFTs were determined for a transvenous lead system and a 300-microF-capacitor defibrillator. In 8 pigs (group 1), DFTs were determined for 5 triphasic waveforms with tilts of 80%, 83%, and 86% and for 1 biphasic waveform. DFTs were determined in another 8 pigs (group 2) for 2 triphasic and 4 biphasic waveforms with tilts of 43%, 49%, and 56%. In both groups, a biphasic waveform from a 140-microF-capacitor defibrillator was also evaluated, and both shock polarities were tested for each waveform. In group 1, with the 300-microF-capacitor defibrillator, the leading-edge voltage and energy stored at DFT were significantly lower for triphasic waveforms with phase-duration ratios of 50/33/17 and an anode at the right ventricular electrode for phase 1 than for biphasic waveforms (P<0.001). In group 2, the stored energy of triphasic waveforms with 56% and 49% tilt was significantly lower than that of biphasic waveforms with the same tilts for anodal but not cathodal phase 1 at the right ventricular electrode. Electrode polarity significantly affected the DFT of triphasic waveforms for both studies. CONCLUSIONS: Some 80% tilt triphasic waveforms defibrillate more efficiently than biphasic waveforms with a 300-microF-capacitor defibrillator. The triphasic waveforms for both groups were not superior to 140-microF-capacitor biphasic waveforms. The efficacy of triphasic waveforms depends on phase durations and electrode polarity.

Pacing after shocks stronger than the upper limit of vulnerability: impact on fibrillation induction.

BACKGROUND: After upper-limit-of-vulnerability (ULV) shocks of the same strength and coupling interval (CI) during the T wave, (1) the epicardial activation pattern (EAP) for the first postshock cycle is indistinguishable between shocks that do (VF) and do not (NoVF) induce ventricular fibrillation (VF) and (2) >/=3 cycles in rapid succession always occur during VF but not during NoVF episodes. To study the role of these rapid cycles, rapid pacing was performed after a shock stronger than the ULV that by itself did not induce rapid cycles and VF. METHODS AND RESULTS: A 504-electrode sock was sutured to the heart in 6 pigs to map EAPs. The S2 shock strength and S1-S2 CI at the ULV were determined by T-wave scanning with an up/down protocol. Ten shocks 50 to 100 V above the ULV (aULV) were delivered at the same S1-S2 CI to confirm that VF was not induced. Then, the postshock interval after aULV shocks was scanned with an S3 pacing stimulus from the LV apex until the shortest S2-S3 CI that captured was reached. This was repeated for S4, S5, etc, until VF was induced. To induce VF, 3 pacing stimuli (S3-S5) with progressively shorter CIs were required; S3 or S3, S4 never induced VF. After cycle S5, which induced VF, 2 EAP types occurred: focal (74%) and reentrant (26%). CONCLUSIONS: At least 3 cycles with short CIs are necessary for VF induction after aULV shocks. Cycles S3-S4 may create the substrate for cycle S5 to initiate VF.

Pathological effects of extensive radiofrequency energy applications in the pulmonary veins in dogs.

INTRODUCTION: The long-term complications of catheter ablation within the pulmonary veins are unknown. The development of pulmonary vein stenosis has recently been described after catheter ablation to treat either chronic or paroxysmal atrial fibrillation. The purpose of this study was to examine the pathological and hemodynamic effects of radiofrequency (RF) energy application within the pulmonary veins. METHODS AND RESULTS: Right heart and transseptal catheterization were performed in 9 anesthetized mongrel dogs. The pulmonary vein ostia were cannulated and pulmonary venous pressure was measured before RF energy application in up to 4 separate pulmonary veins. Animals were euthanized at intervals of 2 to 4 weeks (n=3), 6 to 8 weeks (n=3), or 10 to 14 weeks (n=3) after ablation. Repeat catheterization before euthanasia demonstrated statistically significant differences in pulmonary capillary wedge pressure, cardiac output, pulmonary vascular resistance, and systemic vascular resistance (P<0.05) compared with the baseline. Luminal narrowing was observed in 22 of 33 pulmonary veins to which RF energy was applied. Of these, 7 were totally occluded, 7 had severe stenosis, and 8 were only minimally narrowed. Histological examination revealed intimal proliferation with organizing thrombus, necrotic myocardium in various stages of collagen replacement, endovascular contraction, and a proliferation of elastic lamina. CONCLUSIONS: Applications of RF current within the pulmonary veins may result in pulmonary vein narrowing or complete occlusion. These observations should be considered in treatment of arrhythmias originating within the pulmonary veins.

Improvement of defibrillation efficacy and quantification of activation patterns during ventricular fibrillation in a canine heart failure model.

BACKGROUND: Little is known about the effects of heart failure (HF) on the defibrillation threshold (DFT) and the characteristics of activation during ventricular fibrillation (VF). METHODS AND RESULTS: HF was induced by rapid right ventricular (RV) pacing for at least 3 weeks in 6 dogs. Another 6 dogs served as controls. Catheter defibrillation electrodes were placed in the RV apex, the superior vena cava, and the great cardiac vein (CV). An active can coupled to the superior vena cava electrode served as the return for the RV and CV electrodes. DFTs were determined before and during HF for a shock through the RV electrode with and without a smaller auxiliary shock through the CV electrode. VF activation patterns were recorded in HF and control animals from 21x24 unipolar electrodes spaced 2 mm apart on the ventricular epicardium. Using these recordings, we computed a number of quantitative VF descriptors. DFT was unchanged in the control dogs. DFT energy was increased 79% and 180% (with and without auxiliary shock, respectively) in HF compared with control dogs. During but not before HF, DFT energy was significantly lowered (21%) by addition of the auxiliary shock. The VF descriptors revealed marked VF differences between HF and control dogs. The differences suggest decreased excitability and an increased refractory period during HF. Most, but not all, descriptors indicate that VF was less complex during HF, suggesting that VF complexity is multifactorial and cannot be expressed by a scalar quantity. CONCLUSIONS: HF increases the DFT. This is partially reversed by an auxiliary shock. HF markedly changes VF activation patterns.

Reduction of atrial defibrillation threshold with an interatrial septal electrode.

BACKGROUND: The standard lead configuration for internal atrial defibrillation consists of a shock between electrodes in the right atrial appendage (RAA) and coronary sinus (CS). We tested the hypothesis that the atrial defibrillation threshold (ADFT) of this RAA-->CS configuration would be lowered with use of an additional electrode at the atrial septum (SP). METHODS AND RESULTS: Sustained atrial fibrillation was induced in 8 closed-chest sheep with burst pacing and continuous pericardial infusion of acetyl-ss-methylcholine. Defibrillation electrodes were situated in the RAA, CS, pulmonary artery (PA), low right atrium (LRA), and across the SP. ADFTs of RAA-->CS and 4 other lead configurations were determined in random order by use of a multiple-reversal protocol. Biphasic waveforms of 3/1-ms duration were used for all single and sequential shocks. The ADFT delivered energies for the single-shock configurations were 1.27+/-0.67 J for RAA-->CS and 0. 86+/-0.59 J for RAA+CS-->SP; the ADFTs for the sequential-shock configurations were 0.39+/-0.18 J for RAA-->SP/CS-->SP, 1.16+/-0.72 J for CS-->SP/RAA-->SP, and 0.68+/-0.46 J for RAA-->CS/LRA-->PA. Except for CS-->SP/RAA-->SP versus RAA-->CS and RAA-->CS/LRA-->PA versus RAA+CS-->SP, the ADFT delivered energies of all of the configurations were significantly different from each other (P:<0. 05). CONCLUSIONS: The ADFT of the standard RAA-->CS configuration is markedly reduced with an additional electrode at the atrial SP.

The spectrum of pathology associated with percutaneous transluminal coronary angioplasty during acute myocardial infarction.

The purpose of this study was to determine at necropsy the morphologic consequences of percutaneous transluminal coronary angioplasty performed during acute myocardial infarction. The heart was examined in four patients who died between 6 hours and 4 days after coronary angioplasty. The patients had angioplasty of the left main coronary artery (one patient), left anterior descending coronary artery (two patients) and left circumflex coronary artery (one patient). Necropsy revealed residual stenosis, intimal hemorrhage and plaque disruption in all four patients. Also noted were distal embolization of plaque elements (two patients) and thrombotic occlusion of the coronary artery (one patient). In conclusion, the morphologic changes after angioplasty are varied. These changes illustrate the mechanisms of angioplasty and some of the complications that can be expected in a small number of cases. The morphologic changes associated with coronary angioplasty are similar in patients undergoing elective or emergency angioplasty although medial dissection was not observed in these patients with an evolving myocardial infarction.

Ventricular defibrillation using biphasic waveforms: the importance of phasic duration.

Biphasic waveforms can be used to defibrillate the heart with less energy than that used by monophasic waveforms. In 14 anesthetized open chest dogs with large contoured defibrillation electrodes, the effect on defibrillation efficacy of varying the duration of the two phases of biphasic waveforms was studied. All combinations of 0, 1, 3.5, 6 and 8.5 ms duration were used for both the first and the second phase except for the meaningless case in which both durations were 0 ms. The 3.5-2 waveform (3.5 ms first phase and 2 ms second phase) was also tested. All the hearts were defibrillated with less than or equal to 5 joules using any of the 25 waveforms. However, biphasic waveforms with the second phase shorter than or equal to the first had significantly lower defibrillation thresholds than did those with the second phase longer than the first or than did monophasic waveforms of approximately the same total duration. A plot of defibrillation threshold current strength versus second phase duration for all biphasic waveforms with a 3.5 ms first phase did not produce a hyperbolic strength-duration curve as seen with monophasic waveforms. To verify these findings, defibrillation dose-response curves were obtained for the 3.5-2, 6-6 and 3.5-8.5 biphasic waveforms in another six dogs. The 50 and 80% successful voltage doses of the 3.5-8.5 waveforms were significantly higher than those of the other two waveforms, which were not different from one another.(ABSTRACT TRUNCATED AT 250 WORDS)

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 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.

The effects of ventricular fibrillation duration and site of initiation on the defibrillation threshold during early ventricular fibrillation.

OBJECTIVES: The purpose of this study was to determine if the defibrillation threshold (DFT) is lower during the first few cycles of ventricular fibrillation (VF) than after 10 s of VF and, if so, if the effect is caused by local or global factors. BACKGROUND: The DFT may be low very early during VF because: (1) for the first few cycles VF arises from a localized region close to a defibrillation electrode where the shock field is strong (local factors), or (2) during early VF the effects of ischemia and sympathetic discharge have not yet fully developed and the heart has not yet completely dilated (global factors). METHODS: Protocol 1 included seven pigs in which a defibrillation electrode and a pacing catheter were both placed in the right ventricular apex. VF was induced by delivering a high current premature stimulus from the pacing catheter that should have caused reentry confined to the right ventricular apex for the first few cycles of VF. A bipolar electrogram was recorded from the tip of the defibrillation catheter. Using a three reversal up-down protocol, the DFT was determined for biphasic shocks delivered after 1, 2, 3, 4, 5, 7, 10, 15, 20 and 25 activations in this electrogram and after 10 s (control). Protocol 2 included seven pigs undergoing the same procedure as in protocol 1 except that an additional pacing catheter was placed in the left ventricle. Defibrillation thresholds were determined after 1, 2, 3, 4 and 5 VF activations following VF induction from the right ventricle (RV) or the left ventricle (LV) and after 10 s (control). RESULTS: In protocol 1, the mean +/- SD DFrs were lower during the first three cycles than after 10 s of VF (3.0 +/- 4.1 J for the first VF cycle vs 15.8 +/- 6.6 J after 10 s of VF, p < 0.05). In protocol 2, the DFF for the first few cycles of VF induced away from the defibrillation electrode in the LV (6.9 +/- 1.4 J for the first VF cycle) was significantly lower than that after 10 s of VF (16.0 +/- 2.2 J), whereas the DFF for the first few cycles induced near the defibrillation electrode in the right ventricular apex was significantly lower (2.3 +/- 2.7 J for the first VF cycle) than that induced from the LV. CONCLUSIONS: This study demonstrates that the DFT is significantly lower during the first few VF cycles of VF than after 10 s of VF and that this decrease may be caused by both local factors and global factors. These results provide an impetus for exploring earlier shock delivery in implantable devices.

The influence of ventricular fibrillation duration on defibrillation efficacy using biphasic waveforms in humans.

OBJECTIVES: The purpose of this study was to prospectively investigate the influence of ventricular fibrillation (VF) durations of 5, 10 and 20 s on the defibrillation threshold (DFT) during implantable cardioverter-defibrillator (ICD) implantation. BACKGROUND: Although the DFT using monophasic waveforms has been shown to increase with VF duration in humans, the effect of VF duration on defibrillation efficacy using biphasic waveforms in humans is not known. METHODS: Thirty patients undergoing primary ICD implantation or pulse generator replacement were randomly assigned to have the DFT determined using biphasic shocks at two durations of VF each (5 and 10 s, 10 and 20 s or 5 and 20 s). RESULTS: There was no statistically significant difference in the mean DFT comparing VF durations of 5 s (9.5+/-6.0 J) and 10 s (10.8+/-7.0 J) (p=0.4). The mean DFT significantly increased from 10.9+/-6.1 J at 10 s of VF to 12.6+/-5.6 J (p=0.03) at 20 s of VF, and from 7.0+/-3.5 J at 5 s of VF to 10.5+/-6.3 J (p=0.04) at 20 s of VF. An increase in the DFT was observed in 14 patients as VF duration increased. There were no clinical characteristics that differentiated patients with and without an increase in the DFT. CONCLUSIONS: Defibrillation efficacy decreases with increasing VF duration using biphasic waveforms in humans. Ventricular fibrillation durations greater than 10 s may negatively affect the effectiveness of ICD therapy.