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Biomedical subjects

William M Smith

Publications and source records attributed to William M Smith.

At least 19 recordsLinked to original sources
PubMed2007

Right-sided vagus nerve stimulation inhibits induced spinal cord seizures.

We have previously shown that left-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. To test our hypothesis that right-sided vagus nerve stimulation will also abort seizure activity, we have initiated seizures in the spinal cord and then performed right-sided vagus nerve stimulation in an animal model. Four pigs were anesthetized and placed in the lateral position and a small laminectomy performed in the lumbar region. Topical penicillin, a known epileptogenic drug to the cerebral cortex and spinal cord, was next applied to the dorsal surface of the exposed cord. With the exception of the control animal, once seizure activity was discernible via motor convulsion or increased electrical activity, the right vagus nerve previously isolated in the neck was stimulated. Following multiple stimulations of the vagus nerve and with seizure activity confirmed, the cord was transected in the midthoracic region and vagus nerve stimulation performed. Right-sided vagus nerve stimulation resulted in cessation of spinal cord seizure activity in all animals. Transection of the spinal cord superior to the site of seizure induction resulted in the ineffectiveness of vagus nerve stimulation in causing cessation of seizure activity in all study animals. As with left-sided vagus nerve stimulation, right-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. Additionally, the effects of right-sided vagus nerve stimulation on induced spinal cord seizures involve descending spinal pathways. These data may aid in the development of alternative mechanisms for electrical stimulation for patients with medically intractable seizures and add to our knowledge regarding the mechanism for seizure cessation following peripheral nerve stimulation.

Animals↗
PubMed2006

Improving performance of HVAC systems to reduce exposure to aerosolized infectious agents in buildings; recommendations to reduce risks posed by biological attacks.

The prospect of biological attacks is a growing strategic threat. Covert aerosol attacks inside a building are of particular concern. In the summer of 2005, the Center for Biosecurity of the University of Pittsburgh Medical Center convened a Working Group to determine what steps could be taken to reduce the risk of exposure of building occupants after an aerosol release of a biological weapon. The Working Group was composed of subject matter experts in air filtration, building ventilation and pressurization, air conditioning and air distribution, biosecurity, building design and operation, building decontamination and restoration, economics, medicine, public health, and public policy. The group focused on functions of the heating, ventilation, and air conditioning systems in commercial or public buildings that could reduce the risk of exposure to deleterious aerosols following biological attacks. The Working Group's recommendations for building owners are based on the use of currently available, off-the-shelf technologies. These recommendations are modest in expense and could be implemented immediately. It is also the Working Group's judgment that the commitment and stewardship of a lead government agency is essential to secure the necessary financial and human resources and to plan and build a comprehensive, effective program to reduce exposure to aerosolized infectious agents in buildings.

Advisory Committees↗
PubMed2006

Chronic myocardial infarction is a substrate for bradycardia-induced spontaneous tachyarrhythmias and sudden death in conscious animals.

INTRODUCTION: Patients with bradycardia can have severe tachyarrhythmias but it is unclear whether bradycardia alone can induce arrhythmias or whether an additional substrate is necessary. While several animal models of ventricular tachycardia (VT) exist, no model has been reported to mimic the clinical condition of spontaneous VT and sudden cardiac death (SCD) in the presence of bradycardia and chronic myocardial infarction (MI) in large animals without manipulation of the autonomic nervous system. We tested the hypothesis that MI and bradycardia cause more spontaneous sustained VT than does bradycardia alone. METHODS AND RESULTS: Sheep (42-56 kg) underwent atrioventricular (AV) node catheter ablation alone (n = 5) or AV node ablation and 150 minutes of angioplasty balloon occlusion of the left anterior descending coronary artery (n = 9). An implantable cardioverter defibrillator delivered rescue shocks and demand pacing at 90 beats per minute for the first week and at 40 beats per minute thereafter. Electrograms were continuously radiotelemetered and recorded for 6 weeks. Acute post-MI VT disappeared by day 4. The sudden bradycardia on day 8 triggered numerous premature ventricular contractions (PVCs) and episodes of sustained VT lasting >30 seconds during the next 5 weeks. There were 43 episodes of sustained VT and no spontaneous ventricular fibrillation (VF) with bradycardia alone. However, in the presence of both MI and bradycardia there were 970 episodes of VT/VF (P < 0.05) and three deaths at days 13, 15, and 34. The average 24-hour count of PVCs was similar at day 7 between the two groups but by days 11 and 40, the PVC counts were 35 times and 4 times greater, respectively, in the presence of bradycardia and chronic MI compared to bradycardia alone. No significant difference in the incidence of PVCs was detected because of large individual variation between the two groups (P = 0.21). A high PVC count did not appear to predict SCD. CONCLUSION: The combination of MI and bradycardia secondary to AV node ablation in sheep produces a higher incidence of VT than bradycardia alone, suggesting that this preparation can serve as a model for the study of VT and sudden cardiac death.

Animals↗
PubMed2005

Measuring surface potential components necessary for transmembrane current computation using microfabricated arrays.

This study was designed to test the feasibility of using microfabricated electrodes to record surface potentials with sufficiently fine spatial resolution to measure the potential gradients necessary for improved computation of transmembrane current density. To assess that feasibility, we recorded unipolar electrograms from perfused rabbit right ventricular free wall epicardium (n = 6) using electrode arrays that included 25-microm sensors fabricated onto a flexible substrate with 75-microm interelectrode spacing. Electrode spacing was therefore on the size scale of an individual myocyte. Signal conditioning adjacent to the sensors to control lead noise was achieved by routing traces from the electrodes to the back side of the substrate where buffer amplifiers were located. For comparison, recordings were also made using arrays built from chloridized silver wire electrodes of either 50-microm (fine wire) or 250-microm (coarse wire) diameters. Electrode separations were necessarily wider than with microfabricated arrays. Comparable signal-to-noise ratios (SNRs) of 21.2 +/- 2.2, 32.5 +/- 4.1, and 22.9 +/- 0.7 for electrograms recorded using microfabricated sensors (n = 78), fine wires (n = 78), and coarse wires (n = 78), respectively, were found. High SNRs were maintained in bipolar electrograms assembled using spatial combinations of the unipolar electrograms necessary for the potential gradient measurements and in second-difference electrograms assembled using spatial combinations of the bipolar electrograms necessary for surface Laplacian (SL) measurements. Simulations incorporating a bidomain representation of tissue structure and a two-dimensional network of guinea pig myocytes prescribed following the Luo and Rudy dynamic membrane equations were completed using 12.5-microm spatial resolution to assess contributions of electrode spacing to the potential gradient and SL measurements. In those simulations, increases in electrode separation from 12.5 to 75.0, 237.5, and 875.0 microm, which were separations comparable to the finest available with our microfabricated, fine wire, and coarse wire arrays, led to 10%, 42%, and 81% reductions in maximum potential gradients and 33%, 76%, and 96% reductions in peak-to-peak SLs. Maintenance of comparable SNRs for source electrograms was therefore important because microfabrication provides a highly attractive methods to achieve spatial resolutions necessary for improved computation of transmembrane current density.

Algorithms↗
PubMed2005

Decrease in fluoroscopic cardiac silhouette excursion precedes hemodynamic compromise in intraprocedural tamponade.

BACKGROUND: Acute pericardial tamponade is a life-threatening complication of invasive cardiovascular procedures. Survival depends on early recognition and treatment. A diagnostic test to detect pericardial fluid accumulation before a significant fall in blood pressure and without contamination of the sterile field would be valuable. OBJECTIVE: We tested the hypothesis that fluoroscopic excursion of the cardiac silhouette decreases early in the course of acute pericardial tamponade and precedes hemodynamic compromise. METHODS: The pericardial space of seven pigs was accessed by a sub-xiphoid puncture. Tamponade was produced by intrapericardial saline infusion at 20-25 mL/minute until the pericardial pressure equalized with right ventricular end diastolic pressure or the systolic blood pressure reached 40 mmHg. Supine fluoroscopic images were obtained every 2 minutes in the left anterior oblique view with simultaneous echocardiography. The fluoroscopic heart silhouette was digitized, and the maximum excursion during the cardiac cycle was quantified by custom software. The qualitative excursion of the fluoroscopic heart silhouette on randomly selected video images was also graded by two independent observers who were blinded to the time course of the experiment and the hemodynamics. RESULTS: During progressive pericardial fluid accumulation, the cardiac silhouette excursion quantified by the custom software (p < 0.001) and by video rating (p < 0.0001) was significantly reduced within 2 minutes. A statistically significant fall in blood pressure compared with baseline did not occur until 6 minutes (89 +/- 21 vs. 121 +/- 15 mmHg, p < 0.001). The interobserver agreement was very close, with a kappa statistic of 0.78. The reduction in cardiac silhouette excursion was apparent as soon as the effusion was detected by echocardiography. CONCLUSION: Cardiac silhouette excursion becomes reduced early in the course of acute pericardial fluid accumulation. This fluoroscopic observation can be used to detect impending pericardial tamponade before hemodynamic collapse.

Acute Disease↗
PubMed2005

Regional variation in capture of fibrillating swine left ventricle during electrical stimulation.

INTRODUCTION: While it has been shown that electrical stimulation can capture a region of myocardium during ventricular fibrillation (VF), the ideal location to stimulate to maximize capture of the fibrillating in vivo left ventricle (LV) is not known. We previously demonstrated a mean directionality to the propagation of VF wavefronts in swine from posterior to anterior LV. We hypothesized that this directionality of VF wavefronts would affect capture of the LV epicardium while stimulating during VF. METHODS AND RESULTS: In seven open-chest swine, during different VF episodes, electrical stimulation was performed singly or simultaneously from two lines of 26 epicardial electrodes, one on the posterior LV adjacent to the posterior descending coronary artery and another on the anterior LV adjacent to the left anterior descending coronary artery. Mapping was performed between the line of stimulating electrodes with 768 recording electrodes 2-mm apart. The incidence and extent of epicardium captured by stimulation through the lines of stimulating electrodes were determined in the mapped region. Capture occurred during 67% of 78 VF episodes. Capture from the posterior LV line was achieved in 88% of the episodes and from the anterior LV line in 44% of the episodes (P = 0.001). The maximum amount of myocardium captured was also much greater for stimulating from the posterior as compared to the anterior LV line (232 +/- 168 mm(2) vs 64 +/- 124 mm(2), P = 0.003). A significant part of the variability in capture was related to the direction of the mean VF wavefront velocity vector in each animal (r = 0.84, P < 0.05). CONCLUSION: Electrical stimulation from the posterior LV resulted in a greater incidence and extent of LV capture than stimulation from the anterior LV. A significant component of the variability in capture is related to the mean direction of VF wavefronts.

Animals↗
PubMed2005

Design and initial evaluation of an implantable sonomicrometer and CW Doppler flowmeter for simultaneous recordings with a multichannel telemetry system.

We have developed a sonomicrometer and continuous wavelength (CW) Doppler flowmeter for a multichannel telemetry system. These developments will enable us to measure ventricular dimension and coronary artery blood velocity, which are valuable parameters to characterize sudden cardiac death (SCD) in ambulatory animal models of ventricular arrhythmias. The design goals for the sensors were accuracy, low power consumption, small size and compatibility with each other. The circuits were designed successfully and tested simultaneously in vivo. The CW Doppler flowmeter draws 9 mA and the sonomicrometer draws 28 mA on a 5-V supply. The ability to measure heart dimension and blood velocity will add significantly to our understanding of the sequence of events leading up to spontaneous sudden cardiac death.

Animals↗
PubMed2005

Mechanisms for the maintenance of ventricular fibrillation: the nonuniform dispersion of refractoriness, restitution properties, or anatomic heterogeneities?

INTRODUCTION: The relative importance of nonuniform dispersion of refractoriness, steep restitution slopes, and anatomic heterogeneities in causing conduction block during ventricular fibrillation (VF) remains unknown. METHODS AND RESULTS: In six open-chest pigs, ventricular refractoriness and restitution curves were estimated from activation recovery intervals (ARIs) calculated from 504 (21 x 24) unipolar electrode recordings 2 mm apart in a plaque sutured to the left ventricular (LV) free wall. A steady-state restitution protocol was performed twice at each of two pacing sites: the LV base and near the left anterior descending artery. VF was electrically induced four times and the incidence of conduction block at each electrode during the first 20 seconds was determined by an automated algorithm. The gradient of the ARI was calculated at each electrode to estimate the spatial dispersion of refractoriness. An exponential curve was fit to the restitution plots of ARIs versus the corresponding diastolic intervals (DIs) for all pacing cycle lengths at each electrode. The locations of epicardial blood vessels were noted after the study. Spatial patterns of conduction block were significantly correlated between the four VF episodes in the same animal (r = 0.66 +/- 0.07, P < 0.05). At the shortest pacing cycle length, the spatial distribution of ARIs, ARI gradients, and restitution slopes was not random but formed clusters of similar values. However, none of these variables was significantly correlated with the incidence of conduction block, even though ARI gradients >2 msec/mm were present between many clusters and approximately 90% of restitution slopes were >1. Instead, conduction block frequently appeared to cluster along epicardial vessels. CONCLUSION: Neither the dispersion of refractoriness nor action potential duration restitution determined during rapid pacing by itself is the major determinant of the location of conduction block during early VF in normal pigs. It may be that these factors interact synergistically with each other as well as with other factors, including anatomic heterogeneities such as those caused by blood vessels, which may be particularly important for the formation of conduction block and maintenance of VF.

Animals↗
PubMed2005

Evidence that activation following failed defibrillation is not caused by triggered activity.

BACKGROUND: Earliest postshock activation following failed defibrillation shocks slightly lower than the defibrillation threshold (DFT) in large animals appears to arise from a focus. We tested the hypothesis that these foci are caused by early or delayed afterdepolarizations (EADs or DADs) by performing epicardial electrical mapping and giving the EAD inhibitor pinacidil or the DAD inhibitor flunarizine to see if the foci were extinguished or altered in timing or location. METHODS AND RESULTS: A sock containing 504 electrodes was placed over the entire ventricular epicardium of 12 open-chested pigs. After the DFT was determined and additional shocks given, pinacidil was administered to 6 pigs and flunarizine to 6 pigs. Then, the DFT was again determined and additional shocks were given. Pinacidil significantly shortened the effective refractory period (ERP) (162 +/- 16 vs 130 +/- 28 msec) and action potential duration (APD(90)) (179 +/- 6 vs 149 +/- 19 msec) and significantly increased the peak frequency of the power spectrum of a left ventricle (LV) electrode during ventricular fibrillation (VF) (9.3 +/- 0.6 vs 10.5 +/- 1.0 Hz), while flunarizine did not significantly alter the ERP (162 +/- 8 vs 167 +/- 18 msec) or APD(90) (187 +/- 12 vs 191 +/- 20) but significantly reduced the peak frequency (9.2 +/- 0.5 vs 7.5 +/- 1.0 Hz). These findings suggest the drugs had their expected electrophysiological effects. However, the DFT was not significantly changed by either drug. Following the same strength shock 10% below the predrug DFT, earliest postshock activation arose in a focal epicardial pattern from the anterior-apical LV both before and after the drugs. The time from the shock until the appearance of this activation was not significantly different before and after either drug. CONCLUSION: The lack of change in DFT as well as the lack of change in the incidence, location, and timing of the postshock focus with sub-DFT strength shocks before and after pinacidil and flunarizine provide evidence that these foci are not caused by triggered activity.

Analysis of Variance↗
PubMed2005

Vagus nerve stimulation for induced spinal cord seizures: insights into seizure cessation.

OBJECT: Vagus nerve stimulation is known to decrease the frequency, duration, and intensity of some types of intracranial seizures in both humans and animals. Although many theories abound concerning the mechanism for this action, the true cause remains speculative. To potentially elucidate a pathway in which vagus nerve stimulation aborts seizure activity, seizures were initiated not in the cerebral cortex but in the spinal cord and then vagus nerve stimulation was performed. METHODS: Ten pigs were anesthetized and placed in the lateral position, and a small laminectomy was performed in the lumbar region. Topical penicillin, a known epileptogenic drug to the cerebral cortex and spinal cord, was applied to the dorsal surface of the exposed cord. With the exception of two animals that were used as controls, once seizure activity was discernible via motor convulsion or increased electrical activity the left vagus nerve, which had been previously isolated in the neck, was stimulated. Following multiple stimulations of the vagus nerve and with seizure activity confirmed, the cord was transected in the midthoracic region and vagus nerve stimulation was performed. Vagus nerve stimulation resulted in cessation of spinal cord seizure activity in all (87.5%) but one experimented animal. Transection of the spinal cord superior to the site of seizure induction resulted in the ineffectiveness of vagus nerve stimulation to cause cessation of seizure activity in all study animals. CONCLUSIONS: The effects of vagus nerve stimulation on induced spinal cord seizures involve descending spinal pathways. The authors believe that this experiment is the first to demonstrate that spinal cord neuronal hyperactivity can be suppressed by stimulation of a cranial nerve. These data may aid in the development of alternative mechanisms for electrical stimulation in patients with medically intractable seizures. Further studies are now necessary to isolate which specific tracts, nuclei, and neurotransmitters are involved in this process.

Animals↗
PubMed2004

Restitution properties during ventricular fibrillation in the in situ swine heart.

BACKGROUND: Although restitution has been hypothesized to determine action potential duration (APD) during ventricular fibrillation (VF), cardiac memory may also be important. METHODS AND RESULTS: Transmembrane recordings were made with a floating microelectrode from the anterior right ventricular wall in 6 pigs during up to 60 seconds of VF. The recordings were divided into 5-second intervals, and APD60 and the diastolic interval (DI) were calculated for each activation cycle throughout each interval. Stepwise linear regression was used to determine how well each APD60 [APD60(n)] was predicted by the 4 previous DIs (n-1, n-2, n-3, n-4) and the 3 previous APD60s (n-1, n-2, n-3). A mean+/-SD of 3+/-1.5 of the variables entered the regression equation. DI(n-1) (70% of intervals) and APD60(n-1) (71% of intervals) appeared most frequently in the regression equations and were the first or second variables entered during the stepwise regression in 87% and 76% of the intervals in which they were present, respectively. The coefficients of DI(n-1) and APD60(n-1) were positive 89% and 98% of the time, respectively. R2 of the regression for all entered variables during all intervals was 0.39+/-0.05. CONCLUSIONS: The high incidence and positive coefficient of DI(n-1) indicate that restitution is important in determining APD during VF, whereas the similarly high incidence and positive coefficient of APD(n-1) indicate that cardiac memory is equally important. The finding that the regression equation accounts for only 39% of the variability of APD indicates that factors other than restitution and memory are also important in determining APD during VF.

Action Potentials↗
PubMed2004

Feasibility of cardiac microimpedance measurement using multisite interstitial stimulation.

This study was designed to test the hypothesis that analyses of central interstitial potential differences recorded during multisite stimulation with a set of interstitial electrodes provide sufficient data for accurate measurement of cardiac microimpedances. On theoretical grounds, interstitial current injected and removed using electrodes in close proximity does not cross the membrane, whereas equilibration of intracellular and interstitial potentials occurs distant from electrodes widely separated. Multisite interstitial stimulation should therefore give rise to interstitial potential differences recorded centrally that depend on intracellular and interstitial microimpedances, allowing independent measurement. Simulations of multisite stimulation with fine (25 microm) and wide (400 microm) spacing in one-dimensional models that included Luo-Rudy dynamic membrane equations were performed. Constant interstitial and intracellular microimpedances were prescribed for initial analyses. Discrete myoplasmic and gap-junctional components were prescribed intracellularly in later simulations. With constant microimpedances, multisite stimulation using 29 total electrode combinations allowed interstitial and intracellular microimpedance measurements at errors of 0.30% and 0.34%, respectively, with errors of 0.05% and 0.40% achieved using 6 combinations and 10 total electrodes. With discrete myoplasmic and junctional components, comparable accuracy was maintained following adjustments to the junctions to reflect uncoupling. This allowed uncoupling to be quantified as relative increases in total junctional resistance. Our findings suggest development of microfabricated devices to implement the procedure would facilitate routine measurement as a component of cardiac electrophysiological study.

Artifacts↗
PubMed2004

Short-acting beta-adrenergic antagonist esmolol given at reperfusion improves survival after prolonged ventricular fibrillation.

BACKGROUND: High catecholamine concentrations are cytotoxic to cardiac myocytes. We hypothesized that myocardial interstitial catecholamine levels are greatly elevated immediately after long-duration ventricular fibrillation (VF), defibrillation, and reperfusion and that the short-acting beta-antagonist esmolol administered at reperfusion would protect against this catecholamine surge and improve survival. METHODS AND RESULTS: In part 1 of this study, catecholamines from myocardial interstitial fluid (ISF) and aortic and coronary sinus plasma were quantified by use of 3H-labeled radioenzymatic assay in 8 open-chest, anesthetized pigs. Eight minutes of electrically induced VF was followed by internal defibrillation and reperfusion. By 4 minutes of VF, ISF norepinephrine increased significantly, from 1.3+/-0.3 to 7.4+/-2.4 ng/mL. Epinephrine increased significantly, from 0.4+/-0.2 to 1.5+/-0.7 ng/mL. ISF norepinephrine and epinephrine peaked at 219.2+/-92.1 and 63.7+/-25.1 ng/mL after defibrillation and reperfusion and decreased significantly to 12.2+/-3.5 and 6.7+/-3.1 ng/mL 23 minutes after defibrillation. Transcardiac catecholamine changes were similar. In part 2, 8 minutes of VF was followed by external defibrillation in anesthetized, closed-chest pigs. Animals received 1.0 mg/kg esmolol (n=8) or saline (n=8) intravenously at the start of cardiopulmonary resuscitation (CPR). Advanced cardiac life support, including CPR and epinephrine, was delivered to both groups. Esmolol before reperfusion improved return of spontaneous circulation and 4-hour survival (7/8 versus 3/8 survivors, chi2 P<0.05). CONCLUSIONS: Transcardiac and ISF norepinephrine and epinephrine levels are briefly massively elevated after 8 minutes of VF, defibrillation, and reperfusion. A short-acting beta-antagonist administered immediately after defibrillation improves return of spontaneous circulation and 4-hour survival after this prolonged VF.

Adrenergic beta-Antagonists↗
PubMed2004

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.

Animals↗
PubMed2004

Epicardial organization of human ventricular fibrillation.

OBJECTIVE: The objective of this study was to test the hypothesis that on the epicardium of the in vivo human heart, ventricular fibrillation (VF) consists of chaotic small wavefronts that constantly change paths. BACKGROUND: Despite the significance of VF to cardiovascular mortality, little is known about the wavefronts that constitute VF in humans. METHODS: In 9 patients undergoing cardiac surgery, a single VF episode was induced by rapid pacing immediately after institution of cardiopulmonary bypass while recordings were made from 504 electrodes spaced 2 mm apart in a 20 cm(2) plaque held against the anterior left ventricle epicardium. A total of 26 segments of VF, each 2 s long, were analyzed. A computer algorithm identified individual wavefronts and classified them into groups that followed similar activation sequences. RESULTS: The mean activation rate was 5.8 +/- 1.8 (mean +/- SD) cycles/s. The wavefronts during each epoch were grouped into 9.4 +/- 7.1 different activation pathways, and 8.3 +/- 2.3 wavefronts followed each pathway. Individual wavefronts spread to activate an area of 5.1 +/- 3.0 cm(2) in the mapped region. The majority of the wavefronts propagated into the mapped region and/or propagated out of the mapped region into adjacent tissue, suggesting that the wavefronts were larger than 5.1 cm(2). Reentry was identified in only 16 of the 26 (62%) 2-s segments, always completed <2 cycles, and lasted for 9.5 +/- 6.6% of these 16 epochs, which is 5.8% of the total duration of all the segments analyzed. CONCLUSION: VF wavefronts on the human epicardium are usually large, repeatedly follow distinct pathways, and only occasionally reenter. If these results for the left ventricular epicardium are representative of those for the entire ventricular mass, they do not support the hypothesis that human VF consists of small, constantly changing wavefronts, but rather suggest that there is significant organization of human VF.

Action Potentials↗
PubMed2004

Activation sequences following failed atrial defibrillation.

OBJECTIVES: The purposes of this study were to examine the first activations following atrial defibrillation shocks to help understand how and where atrial fibrillation (AF) relapsed following failed shocks and to assess the difference in postshock activation between failed and successful shocks. BACKGROUND: While many studies have investigated the mechanism of ventricular defibrillation, much less is known about the mechanisms of AF. METHODS: Sustained AF was induced electrically after pericardial infusion of methylcholine in 10 sheep. Biphasic subthreshold shocks were delivered to three configurations: right atrium to distal coronary sinus (RA-CS), sequential shocks with RA-CS as the first pathway followed by proximal CS to superior vena cava as the second pathway (Sequential), and right ventricle to superior vena cava plus can (V-triad). In eight sheep, global atrial mapping was performed with 504 electrodes spaced 3 to 4 mm apart. RESULTS: Earliest postshock activations mostly arose from the left atrium for V-triad but arose from either atrium for RA-CS and Sequential. Preshock AF cycle lengths were significantly shorter at the earliest activation sites than at seven of eight other sites globally distributed over both atria. In all type B successful episodes in which one or more rapid activations occurred after the shock and in 50 of the 72 failed episodes analyzed, activation fronts spread away from the earliest site in a focal pattern, and discrete nonfragmented activation complexes were present in the first derivatives of the electrograms. In the other 22 failed episodes, earliest activation fronts spread in a nonfocal pattern, and earliest postshock electrogram derivatives were fractionated. To better interpret the activation pattern in the fragmented regions, a 504 electrode plaque with 1.5-mm electrode spacing was placed on the right atrial appendage in two additional sheep. In 11 of 108 failed episodes, earliest postshock activation appeared inside the plaque and spread in a focal pattern with nonfragmented electrogram derivatives in 10 episodes and in a reentrant pattern with fragmented electrogram derivatives in the other. CONCLUSIONS: (1) The electrode configuration influenced the location of earliest postshock activation. (2) Earliest postshock activation occurred where the preshock AF cycle length was short. (3) Earliest activations following all type B successful and most failed episodes were not fragmented and spread in a focal pattern. (4) The region of earliest postshock activation in the failed episodes without a focal postshock activation pattern exhibited regions of fragmented electrogram derivatives that may represent conduction block and possibly reentry.

Animals↗
PubMed2004

Comparison of conventional and biventricular antitachycardia pacing in a geometrically realistic model of the rabbit ventricle.

INTRODUCTION: ICDs often are programmed with antitachycardia pacing (ATP) as the first response to ventricular tachycardia (VT). Many ICDs have an additional lead available for ventricular pacing. We hypothesized that using the additional lead for ATP would improve therapy by advancing the orthodromic wavefront, thereby reducing the size of the excitable gap and inducing block of all reentrant activity. METHODS AND RESULTS: Monomorphic VT was initiated in a thin-walled model of rabbit ventricular myocardium that included an apical infarct and anatomically realistic dimensions. ATP with up to eight pulses was delivered at 90% of VT cycle length to one (conventional) or two (biventricular) stimulation areas. Stimulation areas were adjusted from 0.017 cm2 to 0.169 cm2 to modulate interactions between the antidromic and VT wavefronts, and between the orthodromic wavefront and the VT's refractory region. During conventional ATP, we found that larger stimulation areas terminated the VT in three pulses. Continued pacing after termination caused VT reinitiation in the reversed direction in some instances. With smaller stimulation areas, conventional ATP simply reset the circuit. During biventricular ATP, larger stimulation areas terminated VT in one pulse. There were no instances of reinitiation with reversal. However, with smaller stimulation areas, prolongation of refractoriness near the additional stimulation area facilitated induction of functional reentry with pathways modified by continued pacing. CONCLUSION: Our modeling suggests that biventricular ATP is superior to conventional ATP under conditions where the additional ventricular lead effectively advances the orthodromic wavefront. Failure to achieve this advancement poses a risk of VT acceleration.

Animals↗
PubMed2004

Evolution of activation patterns during long-duration ventricular fibrillation in dogs.

Although resuscitation for sudden cardiac arrest attempts are frequently not instituted for several minutes after the onset of ventricular fibrillation (VF), previous mapping studies have examined only the first 40 s of VF or have involved isolated perfused hearts that did not become ischemic during VF. We applied quantitative pattern analysis to mapping data throughout the first 10 min of VF acquired from a 21 x 24 unipolar electrode array located on the ventricular epicardium of six open-chest dogs. The following twelve descriptors were continuously quantified: 1) number of wavefronts, 2) incidence of reentry, 3) wavefront propagation velocity, 4) incidence of breakthrough/focus, 5) incidence of block, 6) mean area activated by the wavefronts, 7) wavefront fractionations, 8) wavefront collisions, 9) multiplicity index, 10) repeatability, 11) negative peak rate of voltage change, and 12) peak frequency of activation. Cluster analysis of these descriptors divided VF into five stages (stages i-v). The values of most descriptors (except block and breakthrough incidence) increased during stage i (1-11 s after VF induction) and maintained high values with rapid dynamic fluctuations during stage ii (12-62 s). Descriptors changed quickly to values indicating greater organization during stage iii (63-86 s), decreased steadily during stage iv (87-310 s), and approached zero during stage v (311-600 s). There was a high incidence of reentry just before, during, and after stage iii. In conclusion, during the first 10 min, VF can be divided into five stages according to the evolution of electrophysiological characteristics. All of the parameters show a rapid deterioration during VF, except for a temporary reversal approximately 1 min after induction when activation briefly became more organized. Thus a quantitative description of activation does not uniformly decrease as VF progresses, but undergo rapid changes and exhibit a brief interval of increased organization after approximately 1 min of VF. Further studies are warranted to determine whether these changes, particularly the increased organization of stage iii, have clinical consequences, such as an alteration in defibrillation efficacy.

Action Potentials↗