Biomedical subjects

W M Smith

Publications and source records attributed to W M Smith.

At least 37 records · Page 2Linked to original sources

PubMed2000

Electrode impedance: an indicator of electrode-tissue contact and lesion dimensions during linear ablation.

Pre-ablation impedance was evaluated for its ability to detect electrode-tissue contact and allow creation of long uniform linear lesions with a multi-electrode ablation catheter. The study consisted of 2 parts, both of which used the in vivopig thigh muscle model. In part 1, a 7 Fr. multi-electrode catheter was held in 3 electrode-tissue contact conditions: (1) non-contact; (2) light contact with a 30g downward force; and (3) tight contact with a 90g downward force. Impedances were measured in unipolar, modified unipolar and bipolar configurations using a source with frequencies from 100Hz to 500kHz. Compared with non-contact, the impedance increased 35 +/- 22 % with 30g contact pressure and 68 +/- 40% when the contact pressure was increased to 90g across the range of frequencies studied. In part 2, the same catheter was held against the tissue with different forces. Pre-ablation impedance was measured using a 10kHz current. Phased radiofrequency energy was applied to the 5 electrodes simultaneously using 10W power at each electrode for 120s. A total of 32 linear lesions were created. The lesion dimensions correlated with pre-ablation impedance. A unipolar impedance > or = 190 Omega indicates 95% possibility to create a uniform linear lesion of at least 3mm depth with our ablation system. We conclude that pre-ablation impedance may be a useful indicator for predicting electrode-tissue contact and the ability to create a continuous and transmural linear lesion with a multi-electrode catheter.

Analysis of Variance↗

PubMed2000

Continuous telemetry from a chronic canine model of sudden cardiac death.

INTRODUCTION: We sought to develop a continuously telemetered animal model of sudden cardiac death (SCD) to study the role of existing infarcts and acute ischemia in fatal arrhythmias. METHODS AND RESULTS: A telemetry system capable of recording eight channels of electrophysiologic data continuously and chronically has been developed. To demonstrate the use of this technology in an animal model of sudden death, 12 anesthetized dogs were instrumented with eight electrodes located in endocardium of the right side of the heart, epicardium of the left ventricle (LV), or in the subcutaneous tissues. The left anterior descending (LAD) coronary artery was occluded for 90 minutes and reperfused to produce LV infarction. A copper wire was placed in the left circumflex (LCX) coronary artery to cause intimal injury in a second arterial bed. The telemetry unit recorded deaths in seven animals between 19 to 64 hours after surgery. Five animals that did not experience SCD by the fifth postoperative day served as controls. There were three modes of SCD: complex ventricular ectopy that degenerated into ventricular fibrillation (VF, n = 4); normal sinus rhythm that suddenly degenerated into VF (n = 1); and bradycardia (RR intervals >1,000 msec) that lasted >3 minutes and preceded VF (n = 2). ST segment changes were significantly greater in the LCX-bed electrograms for tachyarrhythmic compared to bradyarrhythmic deaths (mean +/- SD; 4.0 +/- 3.4 mV and 0.2 +/- 0.8 mV, respectively). Fast Fourier transform showed the peak frequency of VF 10 seconds after onset was significantly higher in the five dogs with initial tachyarrhythmias compared with the VF that followed profound bradycardia (6.5 +/- 3.1 Hz and 3.7 +/- 0.6 Hz, respectively). Computer-assisted planimetry of postmortem heart slices revealed that infarcts in the two dogs with bradycardic events were larger (19.7% +/- 2.2% of the LV and septal mass) than in the five dogs with tachyarrhythmias (7.7% +/- 2.4%) or in the five control dogs (11.9% +/- 8.1%). CONCLUSION: It is possible to record via telemetry the events leading to SCD in an animal model. Continuous telemetry monitoring demonstrated that both tachyarrhythmias and bradyarrhythmias ultimately resulted in VF in an animal model of SCD. Animals with tachyarrhythmic deaths had greate ischemia in the LCX bed, smaller preexisting infarcts, and higher VF peak frequency than animals with bradyarrhythmic deaths.

Animals↗

PubMed2000

Fibrillation is more complex in the left ventricle than in the right ventricle.

INTRODUCTION: The mechanisms that maintain ventricular fibrillation (VF) are not completely understood. It has been proposed that increased ventricular wall thickness destabilizes VF wavefronts and therefore is an important determinant of VF activation patterns. We hypothesized that if this is the case, then VF patterns on the thin-walled right ventricle (RV) should be simpler than those on the thick-walled left ventricle (LV). METHODS AND RESULTS: In seven open chest pigs, we mapped VF simultaneously from two epicardial recording arrays, one on the RV and one on the LV. Each array contained 504 unipolar electrodes (in a 21 x 24 grid) spaced by 2 mm. We used specialized pattern analysis methods to compute quantitative descriptors of RV and LV activation patterns. Our data show that VF is more organized in the RV than the LV, containing fewer, larger wavefronts that follow fewer distinct pathways and are less likely to fragment or collide with other wavefronts. The incidence, size, and cycle length of reentrant circuits were similar in the two ventricles, but RV reentry persisted for more cycles. These results are not predicted by the differences in electrophysiologic properties between LV and RV that have been reported in mammalian hearts. CONCLUSION: The geometry of the ventricular wall, particularly wall thickness, is an important determinant of VF activation patterns.

Action Potentials↗

PubMed2000

Direct medical cost of chronic obstructive pulmonary disease in the U.S.A.

The aim of this study was to estimate the direct medical costs of chronic obstructive pulmonary disease (COPD) in the United States using a public-payor perspective. Cost estimates were derived separately for 10 components of care using national survey databases and valued using Medicare and Medicaid reimbursement rates. COPD affects 15 million people in the U.S.A. and the total annual U.S. payment for care is $6.6 billion. Approximately one-third ($2.3 billion) is due to the cost of long-term oxygen therapy, one-quarter is attributed to hospitalizations and inpatient physician services ($1.9 billion), and one-seventh ($942 million) is due to nursing home stays. Other annual costs are outpatient physician visits ($480 million), prescription medications ($462 million), home healthcare ($309 million), emergency department visits ($148 million), outpatient diagnostic procedures ($55 million) and hospice care ($28 million). The cost of COPD is therefore considerable. The significant expenditure for long-term oxygen therapy indicates that disease severity is a major driver of costs. However, the cost of hospitalizations, nursing home stays, emergency department and physician visits are not insignificant.

Aged↗

PubMed2000

Hemispheric and facial asymmetry: gender differences.

Facial asymmetry (facedness) of female and male college students was investigated. Comparisons of facedness were made between 45 female and 45 male Dartmouth undergraduates. Facedness was defined in terms of the relative sizes (in square centimetres) of the two hemifaces. Data were derived from measurements of two-dimensional frontal photographs of the subjects. Reliable differences in facedness were found between the two groups. The females on average were found to be right faced, the males left faced. This difference was interpreted in terms of the contralateral control (below the eyes) of the two sides of the face by the two hemispheres, and the known differences in cognitive processing by the two hemispheres (left hemisphere-verbal; right hemisphere-visuospatial) in females and males. The observed difference in facial asymmetry between the two sexes is attributed to differential muscular development of the two sides of the face as related to the factors just noted. Suggestions are made for further research on facedness, particularly in relation to different age groups.

Journal Article↗

PubMed2000

A telemetry system for the study of spontaneous cardiac arrhythmias.

The characteristics of spontaneous cardiac arrhythmias leading to sudden cardiac death are largely unknown. To study arrhythmias in animal models, an eight-channel implantable radio telemetry system has been developed to record continuously cardiac electrograms over a period of weeks to months, with maintenance restricted to changing batteries. The inputs are connected in a unipolar manner. Each channel has a gain of fifty and is AC coupled, band limited to 0.07-260 Hz. The signals are digitized with 12 bits resolution at 1000 samples/s. The amplifiers, analog-to-digital converter, and control logic are packaged in an implantable unit. An umbilical cable is passed through the skin to an external backpack unit for power and data transmission. A custom serial interface card, a PC/104 form factor 25-MHz 80386-based single-board computer with a PCMCIA wireless local area network (WLAN) card, and battery power supply make up the backpack. Data are read into the parallel port of the computer, buffered, then transmitted over the WLAN to the laboratory network where it can be analyzed and archived. Approximately 12 h of 14,000 bytes/s data can be collected with each set of batteries. The system is suitable for continuous monitoring of animal models of spontaneous arrhythmias and sudden cardiac death.

Animals↗

PubMed2000

Estimation of 3-D conduction velocity vector fields from cardiac mapping data.

A method to estimate three-dimensional (3-D) conduction velocity vector fields in cardiac tissue is presented. The speed and direction of propagation are found from polynomial "surfaces" fitted to space-time (x, y, z, t) coordinates of cardiac activity. The technique is applied to sinus rhythm and paced rhythm mapped with plunge needles at 396-466 sites in the canine myocardium. The method was validated on simulated 3-D plane and spherical waves. For simulated data, conduction velocities were estimated with an accuracy of 1%-2%. In experimental data, estimates of conduction speeds during paced rhythm were slower than those found during normal sinus rhythm. Vector directions were also found to differ between different types of beats. The technique was able to distinguish between premature ventricular contractions and sinus beats and between sinus and paced beats. The proposed approach to computing velocity vector fields provides an automated, physiological, and quantitative description of local electrical activity in 3-D tissue. This method may provide insight into abnormal conduction associated with fatal ventricular arrhythmias.

Animals↗

PubMed2000

Distributed computing for membrane-based modeling of action potential propagation.

Action potential propagation simulations with physiologic membrane currents and macroscopic tissue dimensions are computationally expensive. We, therefore, analyzed distributed computing schemes to reduce execution time in workstation clusters by parallelizing solutions with message passing. Four schemes were considered in two-dimensional monodomain simulations with the Beeler-Reuter membrane equations. Parallel speedups measured with each scheme were compared to theoretical speedups, recognizing the relationship between speedup and code portions that executed serially. A data decomposition scheme based on total ionic current provided the best performance. Analysis of communication latencies in that scheme led to a load-balancing algorithm in which measured speedups at 89 +/- 2% and 75 +/- 8% of theoretical speedups were achieved in homogeneous and heterogeneous clusters of workstations. Speedups in this scheme with the Luo-Rudy dynamic membrane equations exceeded 3.0 with eight distributed workstations. Cluster speedups were comparable to those measured during parallel execution on a shared memory machine.

Action Potentials↗

PubMed2000

Signal averaging in Wolff-Parkinson-White syndrome: evidence that fractionated activation is not necessary for body surface high-frequency potentials.

It is commonly assumed that the presence of high frequency components in body surface potentials implies that fractionated activation fronts, caused by heterogeneously viable tissue, are present in the heart. However, it is possible that non-fractionated activation fronts can also give rise to high frequency surface potentials and that the relative amount of high frequency power is related to the complexity of the activation sequence. In a test of this idea, averaged body surface potentials were recorded during the entire QRS complex of nine Wolff-Parkinson-White (WPW) patients in situations in which fractionated activation fronts should not have been present, but which represent increasing degrees of complexity of ventricular activation: (1) postoperative ectopic pacing from subepicardial wires placed during surgery, when a single coherent activation front was present throughout most of the QRS; (2) Preoperative preexcited rhythm, when a single coherent activation front was present for one portion of the QRS (the delta wave); and (3) postoperative normal rhythm, when two or more activation fronts were present in the ventricles throughout most of the QRS. For comparison, averaged body surface potentials were also analyzed during the last 40 ms of the QRS complex and the ST segment of 14 postinfarction patients with chronic ventricular tachycardia. In the patients with WPW syndrome, relatively high frequency content increased (attenuation -36.7 vs -27.2 vs -18.3 dB) and QRS width decreased (160.7 vs 125.9 vs 94.1 ms) significantly from paced to preoperative to postoperative beats. Significant high frequency content was present in all cases, showing that coherent activation fronts can give rise to high frequencies. Interestingly, the postoperative QRS of WPW patients contained a larger proportion of high frequency power than did the late potentials of the patients with ventricular tachycardia. Thus, while the presence of late fractionated body surface potentials may be a marker for ventricular tachycardia, these potentials by themselves do not necessarily signify that the underlying cardiac activation giving rise to these signals is fractionated.

Body Surface Potential Mapping↗

PubMed2000

Three-dimensional mapping of spontaneous ventricular arrhythmias in a canine thrombotic coronary occlusion model.

INTRODUCTION: Ventricular tachycardia (VT) and ventricular fibrillation (VF) induced by thrombotic coronary occlusion were mapped in three dimensions in ten dogs. METHODS AND RESULTS: Thrombotic occlusion was induced using a wire to deliver current to the proximal left circumflex artery (LCX). In nine dogs, nonsustained VT (NSVT) arose from numerous focal sites. Sustained VT was initiated in six dogs (VT group) by a focus near or in the ischemic region. VT was maintained by a focus in the ischemic border in three dogs and by macroreentry that involved both the ischemic and nonischemic regions in the other three dogs. In five dogs, VT degenerated into VF due to intramural reentry in different locations. Mean total activation time (AT), the time for activation to traverse the ventricles, for a sinus beat when LCX current was first applied was 40 +/- 4 msec. In the four dogs in which VT occurred 3 to 7 minutes after total occlusion, sinus AT increased to 98 to 146 msec just before VT. Sinus AT in the four dogs without VT was always <98 msec. Mean AT of the first ten cycles of VT was significantly longer in those VTs that degenerated into VF (169 +/- 29 msec) than in those that did not (81 +/- 12 msec). CONCLUSION: Thrombotic LCX occlusion induced NSVT in 90%, VT in 60%, and VF in 50% of dogs. Focal mechanisms caused most NSVTs and VT initiation. VT was maintained by a focus near or in the ischemic region or by macroreentry involving both the ischemic and nonischemic regions. AT identified animals in which VT occurred soon after LCX occlusion and in which VT progressed to VF.

Animals↗

PubMed2000

Over-representation of PPARgamma sequence variants in sporadic cases of glioblastoma multiforme: preliminary evidence for common low penetrance modifiers for brain tumour risk in the general population.

PPARgamma, the gamma isoform of a family of peroxisome proliferator activated receptors, plays a key role in adipocyte differentiation. Recently, its broad expression in multiple tissues and several epithelial cancers has been shown. Further, somatic loss of function mutations in PPARgamma have been found in primary colorectal carcinomas. We sought to determine if somatic high penetrance mutations in this gene might also play a role in glioblastoma multiforme (GBM). We also examined this gene to determine if common low penetrance polymorphic alleles might lend low level susceptibility to GBM in the general population. No somatic high penetrance mutations were detected in 96 sporadic GBMs. However, polymorphic alleles at codons 12 and 449 were significantly over-represented among the 27 unrelated American patients with sporadic GBM compared to 80 race matched controls. While nine (33%) were heterozygous for the P12A variant, c.34C/G (cytosine to guanine change at nucleotide 34), 12 (15%) controls were heterozygous for P12A (p<0.05). Similarly, 13 of 26 (50%) glioblastoma patients compared to 10 of 80 (12%) normal controls were found to have the heterozygous H449H polymorphism (p<0.001). The over-representation of H449H in glioblastoma patients was confirmed with a second validation set of American patients. When both American series were combined, polymorphic H449H was over-represented among cases versus controls (p<0.001) and there was a similar trend (p=0.07) for P12A. The precise mechanism for this association is unknown but these PPARgamma polymorphisms may be acting in a low penetrance predisposing manner. However, these associations were not found in a German population, possibly arguing that if these variants are in linkage disequilibrium with a third locus, then this effect is relatively new, after the settlement of the American colonies.

Alleles↗

PubMed1999

PTEN suppresses breast cancer cell growth by phosphatase activity-dependent G1 arrest followed by cell death.

PTEN/MMAC1/TEP1, a tumor suppressor gene, is frequently mutated in a variety of human cancers. Germ-line mutations of phosphatase and tensin homolog, deleted on chromosome ten (PTEN) are found in two inherited hamartoma tumor syndromes: Cowden syndrome, which has a high risk of breast, thyroid, and other cancers; and Bannayan-Zonana syndrome, a related disorder. PTEN encodes a phosphatase that recognizes both protein substrates and phosphatidylinositol-3,4,5-triphosphate. The lipid phosphatase activity of PTEN seems to be important for growth suppression through inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. We established clones with stable PTEN expression controlled by a tetracycline-inducible system to examine the consequences of increased levels of wild-type and mutant PTEN expression in a well-characterized breast cancer line, MCF-7. When we overexpressed PTEN in MCF-7, growth suppression was observed, but only if PTEN phosphatase activity is preserved. The initial growth suppression was attributable to G1 cell cycle arrest, whereas subsequent growth suppression was attributable to a combination of G1 arrest and cell death. Of note, the decrease in Akt phosphorylation preceded the onset-of suppression of cell growth. Treatment of MCF-7 cells with wortmannin, a PI3K inhibitor, caused cell growth inhibition in a way similar to the effects of overexpression of PTEN in this cell. In general, the inverse correlation between PTEN protein level and Akt phosphorylation was found in a panel of breast cancer cell lines. Therefore, PTEN appears to suppress breast cancer growth through down-regulating PI3K signaling, which leads to the blockage of cell cycle progression and the induction of cell death, in a sequential manner.

Androstadienes↗

PubMed1999

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).

Action Potentials↗

PubMed1999

Incidence, evolution, and spatial distribution of functional reentry during ventricular fibrillation in pigs.

Functional reentry has been hypothesized to be an underlying mechanism of ventricular fibrillation (VF); however, its contribution to activation patterns during fully developed VF is unclear. We applied new quantitative pattern analysis techniques to mapping data acquired from a 21 x 24 unipolar electrode array (2-mm spacing) located on the ventricular epicardium of 7 open-chest, unsupported pigs. Data epochs 4 seconds long beginning 1, 10, 20, 30, and 40 seconds after electrical induction were analyzed. Reentrant circuits were automatically identified and quantified. We found that 2.3% of activation pathways could unambiguously be classified as reentrant. From scaling analysis, an additional 28% of the pathways may also have been reentrant. Reentry was short-lived with 1.5+/-1.5 (mean+/-SD) complete cycles per circuit. The fraction of reentrant pathways, number of cycles per circuit, cycle duration, and area and perimeter of the cores all increased significantly as VF progressed. Core drift speed decreased significantly. Neither the orientation of the cores nor the direction of drift was well predicted by the epicardial fiber orientation (r2=0.108 and 0.138, respectively, by linear regression). Reentrant circuits were clustered in regions of the epicardium. We conclude the following: (1) Epicardial reentry is relatively uncommon and short-lived during VF, suggesting either that sustained reentry is transmural or that mechanisms governing sustained reentry are relatively unimportant to the dynamics of VF. (2) Reentrant circuits become more common, larger, and longer-lived as VF progresses, which may explain a recently observed increase in VF organization during the first minute of VF. (3) The conditions necessary to induce and sustain reentry are distributed nonuniformly.

Animals↗

PubMed1999

Predicting the relative efficacy of shock waveforms for transthoracic defibrillation in dogs.

STUDY OBJECTIVE: Previous work has shown that a passive membrane model using a parallel resistor-capacitor circuit is capable of predicting optimal waveforms for transvenous defibrillation. This study tested the ability of that model to predict optimal waveforms for transthoracic defibrillation. METHODS: This study was divided into 3 parts, each of which determined transthoracic defibrillation thresholds (DFTs) in 6 dogs for several different waveform shapes and durations. For each part, strength-duration relationships were determined from both experimental and model data and then compared with test model predictions. Part 1 DFTs were determined at various durations for 3 different monophasic waveforms-the ascending ramp, descending ramp, and square waveform. Part 2 DFTs were determined for 3 biphasic waveforms. Phase 1 was a 30-ms ascending ramp, and phase 2 was an ascending ramp, a descending ramp, or a square waveform. Part 3 DFTs were determined for 3 biphasic waveforms with very short second-phase durations. Phase 1 was a 30-ms ascending ramp, and phase 2 was a descending ramp. RESULTS: For part 1, the model was able to predict the relative defibrillation efficacy of the 3 monophasic waveforms ( P < .05). For parts 2 and 3, the model was able to predict the biphasic waveforms with the lowest DFTs. These predictions were based on the criterion that the model response at the end of the second phase should return to or slightly pass the model response value at the beginning of the first phase. CONCLUSION: The resistor-capacitor model successfully predicted the relative defibrillation efficacy of several different waveforms delivered transthoracically.

Analysis of Variance↗

PubMed1999

Loss-of-function mutations in PPAR gamma associated with human colon cancer.

The gamma isoform of the peroxisome proliferator-activated receptor, PPAR gamma, regulates adipocyte differentiation and has recently been shown to be expressed in neoplasia of the colon and other tissues. We have found four somatic PPAR gamma mutations among 55 sporadic colon cancers: one nonsense, one frameshift, and two missense mutations. Each greatly impaired the function of the protein. c.472delA results in deletion of the entire ligand binding domain. Q286P and K319X retain a total or partial ligand binding domain but lose the ability to activate transcription through a failure to bind to ligands. R288H showed a normal response to synthetic ligands but greatly decreased transcription and binding when exposed to natural ligands. These data indicate that colon cancer in humans is associated with loss-of-function mutations in PPAR gamma.

Amino Acid Substitution↗

PubMed1999

Automatic detection of conduction block based on time-frequency analysis of unipolar electrograms.

UNLABELLED: It is commonly thought that lethal tachyarrhythmias, such as ventricular fibrillation (VF), are perpetuated by functional reentry, which occurs when an activation wave blocks and rotates around tissue that is excitable (i.e., functional block). Electrograms recorded near these regions typically contain two sequential deflections representing activation on either side of the block. By detecting these "double potentials," we hypothesize that functional block can be detected by a single electrode. METHODS: Unipolar electrograms were recorded from a 24 x 21 mapping array on the intact ventricular epicardium of five pigs during electrically-induced VF. The short time Fourier Transform (STFT) of each electrogram was analyzed to identify double potentials. To evaluate the performance of the STFT algorithm, conduction block was located in activation maps using a minimum conduction velocity criterion (10 cm/s) and then compared to the results of the STFT algorithm. RESULTS: The STFT algorithm detected conduction block with a sensitivity of 0.74 +/- 0.12 and a specificity of 0.99 +/- 0.00. CONCLUSION: We have developed an automated algorithm that can detect functional block during VF from a single electrode recording. Possible applications include fast, objective identification of block in mapping data and realtime localization of reentrant substrates using mapping catheters.

Algorithms↗

PubMed1999

Inducibility of sustained ventricular tachycardia in a closed-chest ovine model of myocardial infarction.

The two goals of this study were (1) to develop a closed-chest animal model of monomorphic ventricular tachycardia; and (2) to investigate the effect of dual site pacing on inducibility of ventricular tachycardia. In the first part of the study, 10 of 14 sheep underwent successful induction of myocardial infarction by temporary balloon occlusion of the left anterior descending coronary artery. After a follow-up period of 21-43 days, sustained monomorphic ventricular tachycardia could be induced during programmed electrical stimulation using a "clinical" stimulation protocol in 8 of the 10 sheep. The number of ventricular tachycardia episodes per animal varied between 5 and 70. Ventricular fibrillation was never induced during programmed electrical stimulation. Ventricular tachycardia episodes lasted from 30 seconds up to 15 minutes and were terminated by antitachycardia pacing or DC cardioversion. In the second part of the study, the effect of dual site stimulation on ventricular tachycardia inducibility was investigated. High current stimuli from an area within the infarcted zone were given with the S1 programmed stimulation protocol. This dual site stimulation showed no effect on ventricular tachycardia induction during programmed electrical stimulation. This animal model shows a high induction rate of sustained monomorphic ventricular tachycardia in the chronic phase of myocardial infarction. The high incidence of ventricular tachycardia inducibility provides a reliable tool to study new techniques for the prevention of ventricular tachyarrhythmias.

Animals↗