An analytical comparison of the information in sorted and non-sorted cosine-tuned spike activity.

Spike sorting is a technologically expensive component of the signal processing chain required to interpret population spike activity acquired in a neuromotor prosthesis. No systematic analysis of the value of spike sorting has been carried out, and little is known about the effects of spike sorting error on the ability of a brain-machine interface (BMI) to decode intended motor commands. We developed a theoretical framework to examine the effects of spike processing on the information available to a BMI decoder. We computed the mutual information in neural activity in a simplified model of directional cosine tuning to compare the effects of pooling activity from up to four neurons to the effects of sorting with varying amounts of spike error. The results showed that information in a small population of cosine-tuned neurons is maximized when the responses are sorted and there is diverse tuning of units, but information was affected little when pooling units with similar preferred directions. Spike error had adverse effects on information, such that non-sorted population activity had 79-92% of the information in its sorted counterpart for reasonable amounts of detection and sorting error and for units with moderate differences in preferred direction. This quantification of information loss associated with pooling units and with spike detection and sorting error will help to guide the engineering decisions in designing a BMI spike processing system.

Liver ablation guidance with acoustic radiation force impulse imaging: challenges and opportunities.

Previous studies have established the feasibility of monitoring radiofrequency (RF) ablation procedures with acoustic radiation force impulse (ARFI) imaging. However, questions remained regarding the utility of the technique in clinically realistic scenarios and at scanning depths associated with abdominal imaging in adults. We address several of these issues and detail recent progress towards the clinical relevance of the ARFI technique. Results from in vitro bovine tissues and an in vivo ovine model are presented. Additional experiments were conducted with a tissue-mimicking phantom and parallel receive tracking techniques in order to further support the clinical feasibility of the method. Thermal lesions created during RF ablation are visualized with high contrast in both in vitro and in vivo hepatic tissues, and radial lesion growth can be monitored throughout the duration of the procedure. ARFI imaging is implemented on a diagnostic ultrasonic scanner, and thus may be a convenient option to guide RF ablation procedures, particularly when electrode insertion is also performed with sonographic guidance.

Real-time three-dimensional intracardiac echocardiography.

Using catheter-mounted 2-D array transducers, we have obtained real-time 3-D intracardiac ultrasound (US) images. We have constructed several transducers with 64 channels inside a 12 French catheter lumen operating at 5 MHz. The transducer configuration may be side-scanning or beveled, with respect to the long axis of the catheter lumen. We have also included six electrodes to acquire simultaneous electrocardiograms. Using an open-chest sheep model, we inserted the catheter into the cardiac chambers to study the utility of in vivo intracardiac 3-D scanning. Images obtained include a cardiac four-chamber view, mitral valve, pulmonic valve, tricuspid valve, interatrial septum, interventricular septum and ventricular volumes. We have also imaged two electrophysiological interventional devices in the right atrium, performed an in vitro ablation study, and viewed the pulmonary veins in vitro.

Is pancreaticoduodenectomy with mesentericoportal venous resection safe and worthwhile?

BACKGROUND: Whether or not superior mesentericoportal venous resection (SM-PVR) associated with pancreaticoduodenectomy (PD) is safe and worthwhile has not been fully confirmed. The aim of the present study was to investigate results of this surgical procedure performed for pancreatic head and periampullary neoplasms. METHODS: As a first analysis, postoperative morbidity and mortality after PD with (n = 31) or without SM-PVR (n = 119) were investigated in 150 patients with pancreatic head and periampullary neoplasms. As a second analysis, rates of margin-negative resection and survival after SM-PVR (n = 21) and without SM-PVR (n = 66) were compared in 87 patients with pancreatic ductal adenocarcinoma of the pancreatic head. In these patients undergoing SM-PVR (n = 21), survival rate was investigated in patients who did (n = 13) and did not (n = 8) undergo a margin-negative resection. RESULTS: In the first analysis, duration of surgery and volume of blood transfused perioperatively were higher in patients undergoing SM-PVR. However, mortality, morbidity rates, and mean hospital stay did not differ between patients who did undergo SM-PVR (31 patients, 3.2%, 48.4%, and 22.2 days, respectively) and who did not (119 patients, 2.5%, 47.1%, 25.9 days, respectively). No postoperative death occurred in the recent part of the present study, since 1994, in patients undergoing SM-PVR. In the second analysis of pancreatic ductal adenocarcinoma, rates of margin-negative resection and 2-year survival did not significantly differ between patients who did and did not undergo SM-PVR (62% and 22%, respectively, versus 73% and 24%). In patients undergoing SM-PVR, survival rate was significantly higher for patients undergoing a margin-negative resection (n = 13) than for patients undergoing a macroscopic or microscopic margin-positive resection (n = 8, 2-year survival = 57.1% versus 0%, P <0.05). CONCLUSION: PD combined with SM-PVR can be performed safely. This surgical procedure is followed by a promising survival rate and can be recommended in order to obtain a margin-negative resection; however, candidates for SM-PVR should be carefully selected.

Locating a catheter transducer in a three-dimensional ultrasound imaging field.

Cardiac procedures rely on fluoroscopy for catheter guidance and visualization. However, fluoroscopy provides poor contrast of myocardial structures and exposes both the patient and health care providers to ionizing radiation. As an alternative to fluoroscopy, real-time three-dimensional (3-D) ultrasound imaging has the potential to provide a safe means for tracking catheter position in 3-D while simultaneously imaging the heart's anatomy. A method is described for locating a catheter-mounted transducer in the 3-D ultrasound imaging field. The distance from the imaging transducer to the catheter transducer is measured by time of flight, while the angular position is determined by a spatial crosscorrelation of the received signals with stored receive profiles. Results from simulations with 20-dB SNR demonstrated a mean accuracy of 0.22 +/- 0.13 mm at a 70-mm range. In vitro testing showed a resolution of 0.23 +/- 0.11 mm at a range of 75 mm and a resolution of 0.47 +/- 0.47 mm at a range of 97 mm. With combined catheter position and imaging, this tracking method has the potential to replace fluoroscopy and enhance interventional procedures.

In vitro temperature map of cardiac ablation demonstrates the effect of flow on lesion development.

This paper presents an in vitro temperature mapping study of bovine cardiac tissue during radiofrequency ablation. The objectives were to: (i) develop a technique for measuring the spatial and temporal temperature distribution in the tissue and in the blood during ablation, and (ii) use the temperature measurements to characterize the effects of fluid flow on lesion dimensions, ablation efficiency, and temperature distributions. In vitro ablation (20 W, 60 s) of bovine cardiac tissue was performed. The tissue was placed in a saline-dextrose solution maintained at 37+/- 0.5 degrees C. The solution also irrigated the tissue surface and simulated blood flow velocities of (i) 30, (ii) 55, and (iii) 85 mm/s. Thermocouple measurements were recorded from 25 and 2 locations in the tissue and in the fluid, respectively. The lowest flow resulted in the largest lesion, the maximum tissue, fluid, and electrode temperature increases, and the highest ablation efficiency. The lesions were 5.8 +/- 0.81, 4.8 +/- 0.84, and 4.4 +/- 1.25 mm deep, and 9.3 +/- 1.07, 7.9 +/- 1.48, and 7.8 +/- 1.27 mm wide for flows (i)-(iii), respectively. The blood and tissue temperature distributions were asymmetric around the ablating electrode axis with higher temperatures on the outflow than on the inflow side. The experimental measurements were used to validate a numeric model of ablation in an accompanying paper.

A three-dimensional finite element model of radiofrequency ablation with blood flow and its experimental validation.

A novel three-dimensional finite element model for the study of radiofrequency ablation is presented. The model was used to perform an analysis of the temperature distribution in a tissue block heated by RF energy and cooled by blood (fluid) flow. This work extends earlier models by including true flow in place of a convective boundary condition to simulate realistic experimental conditions and to improve the prediction of blood temperatures. The effect of fluid flow on the temperature distribution, the lesion dimensions, and the ablation efficiency was studied. Three flow velocities were simulated: (i) 30, (ii) 55, and (iii) 85 mm/s. The modeling results were validated qualitatively and quantitatively with in vitro data. The correlation coefficients between the modeling and the experimental temperature measurements were 0.98, 0.97, and 0.95 for flows (i)-(iii), respectively. The slopes were 0.89, 0.95, and 1.06, and the mean root mean square differences between modeling and experimental temperature measurements were 17.3% +/- 11.6%, 15.8% +/- 13.4%, and 18.8% +/- 14.9% for flows (i)-(iii), respectively. A comparison of temperature distribution obtained with a convective boundary versus inclusion of fluid motion showed that the convective boundary resulted in a similar tissue temperature distribution, but overestimated fluid temperatures and lacked the flow asymmetry seen in the true flow model.

Existence of bistability and correlation with arrhythmogenesis in paced sheep atria.

INTRODUCTION: Studies of the electrical dynamics of cardiac tissue are important for understanding the mechanisms of arrhythmias. This study uses high-frequency pacing to investigate the dynamics of sheep atria. METHODS AND RESULTS: A 504-electrode mapping plaque was affixed to the right atrium in six sheep. Cathodal pacing stimuli were delivered to the center of the plaque. Pacing period (Tp) was decreased from 275 +/- 25 msec to 75 +/- 25 msec and then increased to 230 +/- 70 msec in steps of either 5 or 10 msec. In all 21 trials in six sheep, the atrium responded 1:1 at longer Tps and 2:1 at shorter Tps. As Tp was decreased, the response switched to 2:1 at a particular Tp. Conversely, as Tp was increased, the response switched back to 1:1 at a particular Tp. Over 21 trials, the 1:1-to-2:1 and 2:1-to-1:1 transitions occurred at 119.5 +/- 18.8 msec and 130.0 +/- 19.1 msec, respectively. This hysteretic behavior yielded bistability windows, 10.5 +/- 7.2 msec wide, wherein 1:1 and 2:1 responses existed at the same Tp. In 15 trials and in all animals, idiopathic wavefronts emanating from outside the mapped region passed through the mapped region. In 13 of those trials, the idiopathic wavefronts occurred at Tps within the bistability window or within 35 msec of its upper or lower limit. CONCLUSION: Bistability windows and idiopathic wavefronts were observed and found to be correlated with each other, suggesting a connection between bistability and arrhythmogenesis.

Temperature-controlled and constant-power radio-frequency ablation: what affects lesion growth?

Radio-frequency (RF) catheter ablation is the primary interventional therapy for the treatment of many cardiac tachyarrhythmias. Three-dimensional finite element analysis of constant-power (CPRFA) and temperature-controlled RF ablation (TCRFA) of the endocardium is performed. The objectives are to study: 1) the lesion growth with time and 2) the effect of ground electrode location on lesion dimensions and ablation efficiency. The results indicate that: a) for TCRFA: i) lesion growth was fastest during the first 20 s, subsequently the lesion growth slowed reaching a steady state after 100 s, ii) positioning the ground electrode directly opposite the catheter tip (optimal) produced a larger lesion, and iii) a constant tip temperature maintained a constant maximum tissue temperature; b) for CPRFA: i) the lesion growth was fastest during the first 20 s and then the lesion growth slowed; however, the lesion size did not reach steady state even after 600 s suggesting that longer durations of energy delivery may result in wider and deeper lesions, ii) the temperature-dependent electrical conductivity of the tissue is responsible for this continuous lesion growth, and iii) an optimal ground electrode location resulted in a slightly larger lesion and higher ablation efficiency.

Registration of three-dimensional cardiac catheter models to single-plane fluoroscopic images.

Transvenous cardiac procedures require accurate positioning of catheters within the geometrically complex cavities of the heart. Recently, nonfluoroscopic catheter tracking technologies have been developed to quantitate the (degrees-of-freedom) three-dimensional positions of intracardiac catheters. This paper presents a projection-Procrustes method to register an animated three-dimensional (3-D) model of multiple intracardiac catheters with a single-plane fluoroscopic image. Applying the computed transformation to the catheter coordinates enables the animated 3-D model of the catheters to be viewed from the same perspective as the fluoroscopic image. Mathematical simulations show that the computed transformation parameters are sensitive to both the position errors in the 3-D catheter coordinates and to the spatial distribution of the catheter-mounted transducers. Simulations with a realistic geometric model of three catheters with four transducers per catheter showed an angular error of 1.91 degrees +/- 0.27 degree for 3-D catheter position errors of 2.0 mm. An in vitro experiment demonstrated the feasibility of the method using a water tank phantom of three catheters and fluoroscopic images taken over an 80 degrees range. The mean angular error was 0.61 degree +/- 0.48 degree. The results of this study indicate that the projection-Procrustes method is a useful tool for registering 3-D catheter tracking models to single-plane fluoroscopic images.

Effect of pacing site on ventricular fibrillation initiation by shocks during the vulnerable period.

The critical point hypothesis for the upper limit of vulnerability (ULV) states that the site of S1 pacing should not affect the ULV S2 shock strength for a single S2 shock electrode configuration but may affect the S1-S2 interval at which sub-ULV shocks induce ventricular fibrillation (VF). Furthermore, early post-S2 activations leading to VF should arise in areas with low potential gradients of similar magnitude, regardless of the S1 site. This hypothesis was tested in 10 pigs by determining ULVs for three S1 sites [left ventricular apex (LVA), LV base (LVB), and right ventricular outflow tract (RVOT)] with one S2 configuration (LVA patch to superior vena cava catheter). T-wave scanning was performed with biphasic S2 shocks incremented from 60 V in 40-V steps and stepped up or down in 20- and 10-V steps. Activations and S2 potential gradients were recorded at 528 epicardial sites. Although shocks just below the ULV induced VF significantly earlier in the T wave when the S1 site was the RVOT than when it was the LVA or LVB, ULVs were not significantly different for the three S1 pacing sites. Early post-S2 activations arose closer to the S2 electrode for weak S2s but moved to distant low potential gradient areas as the S2 strengthened. Just below the ULV, early post-S2 activations arose in the RVOT when the S1 site was the LVA or LVB but arose along the RV base when the S1 site was the RVOT. Early site potential gradients were not significantly different just below the ULV (LVA: 8.2 +/- 4.1 V/cm; LVB: 8.6 +/- 4. 9 V/cm; RVOT: 8.7 +/- 4.4 V/cm). At the ULV, early post-S2 activations arose from the same areas but did not induce VF. The results support the critical point hypothesis for the ULV. For this S2 configuration, no single point in the T wave could be used to determine the ULV for all S1 sites.

Effect of skin electrode location on radiofrequency ablation lesions: an in vivo and a three-dimensional finite element study.

OBJECTIVES: To assess the effect of skin electrode location on radiofrequency (RF) ablation lesion dimensions and energy requirements. BACKGROUND: Little is known about the effects of skin electrode location on RF ablation lesion dimensions and efficiency. METHODS AND RESULTS: Temperature-controlled ablation at 60 degrees C for 60 seconds was performed in six sheep. Paired lesions were created in the lateral, anterior, posterior, and septal walls of both the ventricles. For group 1 lesions, the skin electrode was positioned directly opposite the catheter tip (optimal). For group 2 lesions, we used either the standard posterior location or an anterior location if the posterior skin electrode location was used for group 1. Group 1 lesions were 5.8+/-0.8 mm deep and 9.3+/-1.9 mm wide, compared with 4.6+/-1.0 mm deep and 7.7+/-1.9 mm wide group 2 lesions (P < or = 0.001). Group 1 lesion dimensions also had less variability. A finite element model was used to simulate temperature-controlled ablation and to study the effect of skin electrode locations on lesion dimensions, ablation efficiency, and blood heating. The optimal location was 1.6 times more efficient, and the volume of blood heated to > or = 90 degrees C was 0.005 mm3 for optimal versus 2.2 mm3 for the nonoptimal location. CONCLUSION: Optimal skin electrode placement: (1) creates deeper and larger lesions; (2) reduces lesion size variability; and (3) decreases blood heating.

Importance of electrode conductive surface area and edge effects on ventricular defibrillation efficacy.

INTRODUCTION: The role of edge effects and electrode surface area of the right ventricular (RV) transvenous lead (TVL) on defibrillation efficacy is unknown. METHODS AND RESULTS: Defibrillation threshold (DFT) testing was conducted randomly in 12 dogs using ring electrode leads in an RV/SVC (superior vena cava) or RV/SVC/patch system. The leads (RV-4, RV-8t, RV-8, RV-15) had electrode surface areas of 20%, 20%, 40%, and 70%, respectively. A computer model predicted the magnitude of electrode surface current (RV-8t > RV-4 > RV-8 > RV-15) and the potential distribution (PD) at four sites: electrode surface (site a) and at 2 mm (b), 4 mm (c), and 8 mm (d) away from the surface. Despite different near-field PDs (sites a, b, c), PDs were nearly identical at site d. Resistance decreased as the surface area increased. DFT energy for the RV-15 lead was lower than the RV-4 and RV-8t. There was no difference between energy requirements for the RV-15 and RV-8 leads. No difference was found in DFT current for each lead. Comparison of the RV-8t and RV-4 leads showed no difference in DFT energy despite a lower resistance and a greater number of edges. CONCLUSIONS: Increasing the RV TVL surface area lowered the resistance. However, surface area coverages > or = 40% did not lower DFT energy. No significant change in DFT current occurred despite different predicted near-field current densities. PDs were nearly identical 8 mm from the electrode surface. Thus, the far-field current density appears to play a more important role in determining defibrillation success.

Application of sonomicrometry and multidimensional scaling to cardiac catheter tracking.

This paper describes a technique for tracking the three-dimensional (3-D) position of a cardiac catheter using sonomicrometry and the mathematical method of multidimensional scaling (MDS). Sonomicrometry is used to measure the distances between ultrasonic transceivers. MDS is then used to calculate the 3-D coordinates of the ultrasonic transceiver locations, including the catheter tip, from the measured distances. Feasibility of catheter tracking was initially studied using simulated data from a geometric model in which the actual coordinates of all transceivers were known. The method was then shown to be feasible in vivo by tracking a catheter-mounted piezoelectric transducer using seven reference crystals sewn to the epicardial surface of a sheep heart. Simulation results indicate that a catheter can be tracked with a root-mean-square (rms) error of 1.51 +/- 0.05 mm and an average-distance error of e = 1.06 +/- 0.27 mm using 12 reference points. In vivo results showed acceptable stress values (G < 0.05) for 95% of the data samples with an average-distance error of e = 0.52 +/- 0.66 mm. These simulation and experimental results show that sonomicrometry and MDS can be used to accurately localize the 3-D position and track the motion of a catheter tip within the heart.

Does reducing capacitance have potential for further miniaturisation of implantable defibrillators?

OBJECTIVE: To determine whether considerably smaller capacitors could replace 125 microF capacitors as the standard for use in implantable defibrillators. METHODS: Measured energy, impedance, voltage, and current delivered were compared at defibrillation threshold in 10 mongrel dogs for defibrillation using 75 microF and 125 microF capacitors alternated randomly. Defibrillation was attempted with biphasic shocks of comparable tilt between an endocardial lead in the right ventricular apex and a "dummy" active can of an experimental implantable device placed in the subpectoral position. RESULTS: A reduction of capacitor size of 40% was associated with an increase in voltage of 21% and in current of 22%. With a 65% tilt, no significant differences were found between the two capacitances with respect to the impedance or energy required for defibrillation. CONCLUSIONS: Multiple advances in electrode material, electrode configuration, shock morphology, and shock polarity have reduced defibrillation energy requirements. Smaller capacitors could be used in implantable cardioverter/defibrillators without a major decrease in effectiveness.

Epicardial sock mapping following monophasic and biphasic shocks of equal voltage with an endocardial lead system.

INTRODUCTION: The reason for the increased defibrillation efficacy of biphasic shocks over monophasic shock is not definitely known. METHODS AND RESULTS: In six anesthetized pigs, we mapped the epicardium after transvenous defibrillation shocks to compare the activation patterns following successful biphasic shocks with unsuccessful monophasic shocks of the same voltage. The heart was exposed and a 510-electrode sock with approximately 4-mm interelectrode spacing was pulled over the entire ventricular epicardium and sutured to the pericardium. Defibrillation catheters were placed in the right ventricular apex and in the superior vena cava. Paired monophasic 12 msec and biphasic 6/6 msec defibrillation shocks were given using an up-down protocol to keep shock strength between the defibrillation thresholds for the two waveforms so that the biphasic shock was successful while the monophasic shock was not. Activation fronts immediately following 60 paired shocks were recorded and analyzed by animated maps of the first derivative of the electrograms. The ventricles were divided into apical (I), middle (II), and basal (III) thirds, and early sites, i.e., the sites from which activation fronts first appeared on the epicardium following the shock, were grouped according to their location. Postshock intervals, i.e., the time from the shock until earliest epicardial activation occurred, were also determined. No ectopic activation fronts followed the shock in 20 biphasic episodes. In the other 40 paired episodes, the number of early sites was smaller after biphasic shocks than after monophasic shocks [monophasic: 198 (total), 3.3 +/- 0.9 (mean +/- SD) per shock episode; biphasic: 67, 1.1 +/- 1.0, P < 0.05]. For biphasic but not monophasic shocks, early sites were less likely to arise from the middle (II) and basal (III) thirds than from the apical third (I) [monophasic: I: 84 (42%), II: 68 (34%), III: 46 (23%); biphasic: I: 49 (73%), II: 10 (15%), III: 8 (12%), P < 0.05]. Postshock intervals were significantly shorter for monophasic shocks (54 +/- 14 msec) than for biphasic shocks (75 +/- 23 msec, P < 0.05). CONCLUSION: The decreased number of activation fronts and the longer delay following the shock for the earliest epicardial appearance of those activation fronts that do occur may be responsible for the increased defibrillation efficacy for biphasic shocks.

Regional capture of fibrillating ventricular myocardium. Evidence of an excitable gap.

Previous investigations have suggested that during ventricular fibrillation (VF) pacing stimuli are incapable of evoking propagated ventricular activations. To determine whether regional myocardial capture could be achieved during rapid pacing in VF, extracellular unipolar potentials were sampled (2 kHz) and recorded from 506 Ag-AgCl electrodes arranged in a rectangular grid (22 x 23, 1.12-mm spacing) embedded in a plaque overlying two pacing electrodes in the epicardium of the anterobasal right ventricle in pentobarbital-anesthetized pigs (25 to 30 kg, n = 6). During separate episodes of electrically induced VF, two bursts of 40 monophasic stimuli (10 mA, 2-millisecond duration) were asynchronously applied to the stimulating electrodes in either a bipolar, unipolar anodal, or unipolar cathodal mode. Evidence of regional capture was provided by (1) animating the first temporal derivative of the extracellular potentials, (2) analyzing inter-beat interval patterns, and (3) employing the Karhunen-Loeve decomposition method to quantify the repetitiveness of spatio-temporal patterns of activation. Regional capture of ventricular myocardium during VF was observed when pacing stimuli fell late in the local myocardial activation interval and when the pacing cycle length was 80% to 115% of the mean subplaque activation cycle length. When myocardial activations became phase locked to the pacing stimuli, repeatable spatiotemporal patterns of activation followed each stimulus. Poincaré sections at the plaque border revealed that during VF prior to pacing, interbeat intervals were irregular but were driven by pacing to stable fixed values at times corresponding to our qualitative declaration of regional capture. A similar correspondence was demonstrated between the time of capture, defined by direct observation of the activation patterns, and a rise in the power contained in the first two spatial modes of a Karhunen-Loeve decomposition. These data demonstrate that appropriately timed stimuli produce regional capture of fibrillating right ventricular myocardium in the pig and support the existence of an excitable gap during VF in this model.

Predicting patterns of epicardial potentials during ventricular fibrillation.

Ventricular fibrillation (VF) is a fatal cardiac arrhythmia, characterized by uncoordinated propagation of activation wavefronts in the ventricular myocardium. Short-term predictions of epicardial potential fields during VF in pigs were attempted using linear techniques, and prediction accuracy was measured at various stages during sustained episodes. VF was induced in five pigs via premature electrical stimulation. Unipolar electrograms were recorded from an epicardial array of 506 electrodes in a 22 x 23 array with 1-mm spacing. Optimal spatial basis functions (modes) and time-varying weighting coefficients were found using the Karhunen-Loeve decomposition. Linear autoregressive (AR) models incorporating the dynamics of only a few spatial modes led to predicted patterns that were qualitatively similar to observed patterns. Predictions were made 0.256 s into the future, based on 0.768 s of past data, over an area of approximately 5 cm2 on the ventricular epicardium. The mean squared error of predictions varied from as much as 1.23 to as little as 0.14, normalized to the variance of the actual data. Inconsistency in long-term forcasts is partly due to the limitations of linear AR models. Changes in predictability, however, were consistent. Predictability varied inversely with spatial complexity, as measured by the mean squared error of a five-mode approximation. Predictability also increased significantly during the first minute of VF.

Alteration of ventricular fibrillation by propranolol and isoproterenol detected by epicardial mapping with 506 electrodes.

INTRODUCTION: We hypothesized that drugs which alter ventricular refractoriness or excitability produce quantifiable changes in ventricular fibrillation. METHODS AND RESULTS: We used a 528-channel mapping system to quantify the effects of the beta-antagonist, propranolol, and the beta-agonist, isoproterenol, on activation patterns in ventricular fibrillation. A plaque of 506 (22 x 23) electrodes spaced 1.12 mm apart and covering about 5% of the ventricular epicardium was sewn to the anterior right ventricle in 18 pigs (30 kg). Propranolol (0.25 to 0.4 mg/kg) increased the refractory period at a right ventricular epicardial site while isoproterenol (3 to 5 micrograms/min) shortened it. Ventricular fibrillation was induced by programmed stimulation, and unipolar electrograms were recorded from the 506 plaque electrodes for 2 seconds beginning 1, 15, and 30 seconds after the onset of fibrillation. Active epicardial recording sites were identified from the first derivative of the unipolar potentials (dV/dt) detected at each electrode. Then, neighboring active sites were grouped into activation fronts by computer analysis. In six pigs the effect of repeated inductions of ventricular fibrillation was assessed by comparing ventricular fibrillation after saline with a preceding control episode of fibrillation. Each activation front excited 40% +/- 46% of the mapped region before blocking. No changes were observed with saline and multiple inductions of fibrillation. In another six pigs, ventricular fibrillation after propranolol was compared with a preceding control episode of fibrillation. Ventricular fibrillation after propranolol exhibited a decreased activation rate per epicardial recording site and fewer activation fronts per second. There was no change in the amount of tissue excited by each activation front or the number of reentry cycles per activation front compared with control. In addition, there was no change in the maximum negative dV/dt detected per activation at an epicardial site. In six pigs ventricular fibrillation during isoproterenol was compared with control episodes of ventricular fibrillation before and 45 minutes after washout of the drug. The control episodes of fibrillation were not different from each other. Compared with control, ventricular fibrillation during isoproterenol exhibited an increased activation rate per epicardial site, an increased amount of tissue excited by each activation front, and an increased maximum negative dV/dt for each activation. There was no change in the number of activation fronts per second or the number of reentry cycles per activation front compared with control. CONCLUSION: Quantitative analysis revealed that propranolol and isoproterenol do not have symmetrically opposite effects on ventricular fibrillation. Propranolol decreased the number of activation fronts while isoproterenol increased the amount of tissue excited by each activation front. Thus, drugs that alter ventricular refractoriness or excitability alter ventricular fibrillation.