The transmural activation sequence in porcine and canine left ventricle is markedly different during long-duration ventricular fibrillation.

BACKGROUND: Humans are more similar in transmural Purkinje and cardiac ion channel distributions to dogs than pigs. The Purkinje network in pigs is transmural but confined to the endocardium in dogs. Little is known about intramural activation during long-duration ventricular fibrillation (LDVF) given these differences. We tested the hypothesis that the transmural activation sequence is similar in sinus rhythm (SR) and LDVF in dogs as well as pigs, but different between species. METHODS AND RESULTS: In six pigs and seven dogs, 50-60 plunge needles (six electrodes, 2-mm spacing) were placed throughout the left ventricle. Unipolar recordings were made for >10 minutes of LDVF. SR and LDVF activation times were grouped into waves by linking activations along each needle. Origin (earliest activation) and propagation direction were determined for each wave. The mean wave origin was significantly more endocardial in dogs than pigs for SR and 1 through 10 minutes of LDVF. Predominant propagation direction in LDVF and SR was endocardial to epicardial in dogs, but the opposite or equal in both directions in pigs. Fastest activation rate was epicardial in pigs, but endocardial in dogs with an increasing endocardial-to-epicardial activation rate gradient as LDVF progressed in dogs but not pigs. CONCLUSIONS: The transmural activation sequence in SR and LDVF is markedly different between pigs and dogs. These differences may be related to differences in Purkinje fiber and ion channel distributions and suggest that dogs are a better model for investigating activation sequences during LDVF, given the similarities with humans.

Estimated global transmural distribution of activation rate and conduction block during porcine and canine ventricular fibrillation.

We quantified ventricular fibrillation (VF) activation rate, conduction block, and organization transmurally in pigs and dogs, whose transmural Purkinje distribution differ. In six pigs and five dogs, 75 to 100 plunge needles, containing four electrodes for the right ventricle (RV) and six electrodes for the left ventricle (LV) and septum, were inserted in vivo. Six VF episodes were electrically initiated and allowed to last for 47 to 180 seconds. From the FFT power spectra, dominant frequency (DF), an estimate of activation rate, and incidence of double peaks (DPI), an estimate of conduction block, were calculated every 8 ms at each electrode. DF was highest at the epicardium and lowest at the endocardium, whereas DPI was highest at the endocardium and lowest at the epicardium for the entire LV and the RV base in both pigs and dogs for the first 70 seconds of VF. This distribution changed little throughout the first 3 minutes of VF in pigs but reversed in dogs by 2 minutes of VF. In conclusion, estimated activation rates and conduction block incidence during VF are not uniformly distributed transmurally. During the first minute of VF, the faster activating LV base epicardium exhibits less estimated block than the slower endocardium, raising the possibility that faster activating epicardium generates wavefronts that drive the endocardium early during VF. Constancy of this pattern in pigs but its reversal by 2 minutes in dogs is consistent with the hypothesis that activation during later VF is driven by Purkinje fibers.

Adaptive pacing during ventricular fibrillation.

While it has been shown that pacing during ventricular fibrillation (VF) can capture a portion of the epicardium, little is known about the characteristics of the area captured or about whether adaptively changing the pacing rate during VF will increase the area captured. In six open-chested pigs, pacing during VF was performed from the center of a plaque containing 504 electrodes 2 mm apart in a21 x 24 array on the anterior right ventricle. Simultaneous recordings from the 504 electrodes were used to construct activation maps from which the area of epicardium captured by pacing was determined. Four pacing algorithms were examined: (1) fixed rate pacing at 95% of the median VF activation rate, (2 and 3) adaptive pacing in which the pacing timing and/or rate is reset in real time if capture is not obtained, and (4) pacing at a slowly increasing rate after initial capture. Regional capture, defined as control of the myocardium under at least 10 plaque electrodes, was achieved in 71% (92/129) of pacing episodes. The incidence of capture was not significantly different for pacing algorithms 1-3. The maximum area captured for each pacing episode with algorithms 1-3 was 3.8 +/- 2.0 cm2(mean +/- SD). Within each animal, the pattern of capture was similar among all pacing episodes, no matter which algorithm was use dr = 0.85 +/- 0.25). The region of greatest capture extended away from the pacing site along the long axis of the myocardial fibers. However, the area of captured epicardium toward the right ventricular side of the pacing electrode was 9.7 times greater than toward the left ventricular side. This principal direction toward the right ventricular side of the pacing electrode was the same direction traveled by the majority of VF activation fronts before capture occurred. The absence of recorded activations at the pacing site for 20 consecutive stimuli predicted 83% of the time that regional capture was present. With algorithm 4, the pacing rate could be increased 7.1%+/- 4.3%while maintaining capture; however, the area of capture progressively decreased as the pacing rate increased. While pacing from the anterior right ventricular epicardium during VF, the area of capture is repeatable and is markedly asymmetrical with almost 10 times as much epicardium captured on the side of the pacing electrode closest to the acute margin of the right ventricle as on the opposite side. This marked asymmetry is associated both with myofiber orientation and with the direction of spread of activation and hence the direction of dispersion of refractoriness during VF just before pacing is initiated. It is possible to perform adaptive pacing algorithms in real time during VF; however, the two adaptive algorithms tested did not capture significantly more epicardium than a simple fixed-rate pacing algorithm. Although it is possible to maintain capture while increasing the pacing rate during VF, the area of capture decreases.

Estimated global epicardial distribution of activation rate and conduction block during porcine ventricular fibrillation.

INTRODUCTION: A proposed mechanism of the maintenance of ventricular fibrillation (VF) determined by studying small hearts or segments of large hearts is that a single stable rotor exists at the site of maximal activation rate, which gives rise to activation fronts that propagate into slower activating regions where they frequently block. We wished to determine if two predictions of this hypothesized mechanism are true during VF in large hearts: (1) there is a single maximum in the distribution of activation rates with the activation rate decreasing with distance away from this maximum; and (2) the incidence of block is greater outside than inside the fastest activating region. METHODS AND RESULTS: Six 25-second episodes of VF from each of six pigs were recorded from 504 electrodes over the entire ventricular epicardium. The electrodes were divided into four zones: left ventricular base and apex (LVB and LVA) and right ventricular base and apex (RVB and RVA). A fast Fourier transform was performed on each electrogram, and the mean activation rate was estimated from the dominant (peak) frequency (DF) and block was estimated to be present during those time intervals when double peaks (DPs) were present in the power spectrum. The zones had statistically significant distributions of DF (LVB>LVA>RVA>RVB) and DP incidence (RVA>RVB>LVA>LVB). CONCLUSION: During VF, the LV base has the highest estimated activation rate and the lowest estimated block incidence, and the RV has the slowest rate but the highest block incidence. This is consistent with the concept of VF being maintained by activation fronts originating from the LV base.

Regional differences in ventricular fibrillation in the open-chest porcine left ventricle.

It has been hypothesized that during ventricular fibrillation (VF), the fastest activating region, the dominant domain, contains a stable reentrant circuit called a mother rotor. This hypothesis postulates that the mother rotor spawns wavefronts that propagate to maintain VF elsewhere and implies that the ratio of wavefronts propagating off a region to those propagating onto it (propoff/propon) should be >1 for the dominant domain but <1 elsewhere. To test this prediction in the left ventricular (LV) epicardium of a large animal, most of the LV free wall was mapped with 1008 electrodes in 7 pigs. VF activation rate was faster in the posterior than in the anterior LV (10.0+/-1.3Hz versus 9.3+/-1.3Hz; P<0.001). The anterior LV had a higher fraction of wavefronts that blocked than did the posterior LV and had a propoff/propon ratio <1 (P<0.001). The mean conduction velocity vectors of the VF wavefronts pointed in the direction from the posterior to the anterior LV. Although these findings favor a dominant domain in the posterior LV, the facts that the anterior LV had a higher incidence of reentry than did the posterior LV and that the posterior LV did not have propoff/propon significantly different from 1 do not. Thus, quantitative regional differences are present over the porcine LV epicardium during VF. Although these differences are not totally consistent with the presence of a dominant domain within the LV free wall, the mean conduction velocity vector is consistent with one in the septum.

Intramural virtual electrodes during defibrillation shocks in left ventricular wall assessed by optical mapping of membrane potential.

BACKGROUND: It is believed that defibrillation is due to shock-induced changes of transmembrane potential (DeltaV(m)) in the bulk of ventricular myocardium (so-called virtual electrodes), but experimental proof of this hypothesis is absent. Here, intramural shock-induced DeltaV(m) were measured for the first time in isolated preparations of left ventricle (LV) by an optical mapping technique. METHODS AND RESULTS: LV preparations were excised from porcine hearts (n=9) and perfused through a coronary artery. Rectangular shocks (duration 10 ms, field strength E approximately 2 to 50 V/cm) were applied across the wall during the action potential plateau by 2 large electrodes. Shock-induced DeltaV(m) were measured on the transmural wall surface with a 16x16 photodiode array (resolution 1.2 mm/diode). Whereas weak shocks (E approximately 2 V/cm) induced negligible DeltaV(m) in the wall middle, stronger shocks produced intramural DeltaV(m) of 2 types. (1) Shocks with E>4 V/cm produced both positive and negative intramural DeltaV(m) that changed their sign on changing shock polarity, possibly reflecting large-scale nonuniformities in the tissue structure; the DeltaV(m) patterns were asymmetrical, with DeltaV-(m)>DeltaV+(m). (2) Shocks with E>34 V/cm produced predominantly negative DeltaV(m) across the whole transmural surface, independent of the shock polarity. These relatively uniform polarizations could be a result of microscopic discontinuities in tissue structure. CONCLUSIONS: Strong defibrillation shocks induce DeltaV(m) in the intramural layers of LV. During action potential plateau, intramural DeltaV(m) are typically asymmetrical (DeltaV-(m)>DeltaV+(m)) and become globally negative during very strong shocks.

Intelligent multichannel stimulator for the study of cardiac arrhythmias.

An intelligent multichannel stimulator (IMS) has been designed and built for use in a cardiac research environment. The device is capable of measuring and responding to cardiac electrophysiological phenomena in real time with carefully timed and placed electrical stimuli. The system consists of 16 channels of sense/stimulation electronics controlled by a digital signal processor (DSP) data acquisition card and a host computer and can be expanded to include more channels. The DSP allows for powerful and flexible algorithms to be implemented for real-time interaction with the cardiac tissue. Although a number of possible uses can be conceived for such a device, the initial motivation was to improve upon attempts to terminate fibrillation by pacing. The IMS was tested in an open-chest animal model, both in sinus rhythm and during fibrillation. It was shown to be an effective research tool by demonstrating the ability to measure and respond to cardiac activations in real time using complex numerical algorithms and appropriately timed stimuli.