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Biomedical subjects

S M Dillon

Publications and source records attributed to S M Dillon.

At least 19 recordsLinked to original sources
PubMed2001

Intracardiac echocardiographic evaluation of ventricular mural swelling from radiofrequency ablation in chronic myocardial infarction: irrigated-tip versus standard catheter.

INTRODUCTION: The production of larger, particularly deeper lesions may improve the success rate for radiofrequency (RF) ablation of post infarction ventricular tachycardia (VT). Therapeutic RF ablation causes left ventricular (LV) mural swelling. This swelling can be detected as increased wall thickness at the ablation site by intracardiac echocardiography (ICE) and correlates with pathologic lesion size. This study compared the extent of mural swelling caused by linear ablation lesions created with irrigated tip and standard RF ablation in a porcine model of healed anterior infarction. METHODS AND RESULTS: In anesthetized closed-chest swine ICE guided multiple RF applications to construct linear lesions at the border zone of the infarct region using an irrigated RF (n=6 swine) and a standard RF (n=6 swine) ablation catheter. 47 individual lesions were created with irrigated RF ablation; 57 lesions created with standard RF ablation. At all sites, wall thickness (measured at end-diastole Pre- and 1 min Post-RF delivery) increased following either irrigated (p<0.0001) or standard (p<0.004) RF deployment. Irrigated RF ablation produced more mural swelling at border zone sites than standard RF ablation (wall thickness increase of 21.2 versus 15.1 %, p<0.003). This difference was more pronounced at RF sites within the infarct (40.7 versus 12.0 %, p<0.0007). Thrombus formation or intramural explosion were not observed; surface crater formation was not more frequent with irrigated compared to standard RF ablation (14/47 versus 12/57 lesions, p=NS). CONCLUSION: Irrigated RF ablation may produce larger lesions than standard RF ablation, particularly for ablation targets within infarcted tissue. ICE imaging provides on line data about the characteristics of the developing lesion which may prove useful in dosing irrigated-tip RF energy application.

Animals↗
PubMed2001

Effects of linear, irrigated-tip radiofrequency ablation in porcine healed anterior infarction.

INTRODUCTION: Radiofrequency (RF) catheter ablation for ventricular tachycardia (VT) in healed infarction is modestly successful. More extensive, anatomically based procedures and irrigated RF delivery may improve outcome. However, limited data exist regarding the characteristics of irrigated RF lesions in infarcted myocardium. This study addresses this shortcoming. METHODS AND RESULTS: Linear lesions were created at the medial border of a healed anterior infarct in eight pigs using irrigated RF energy guided by sinus rhythm electroanatomic voltage mapping and intracardiac echocardiography (ICE). Lesion morphology and effects on ventricular function were assessed with ICE imaging and pathologic analysis (n = 5). The response to programmed stimulation also was determined before and after linear lesions (n = 6). A mean of 9.4 +/- 1.3 RF applications created linear lesions 37.0 +/- 10.6 mm long, 5 to 12 mm wide, and 4 to 8 mm deep. Thrombus formation was not observed. Lesion delivery resulted acutely in increased local wall thickness at the RF site (26.9% +/- 27.5%; P < 0.0001) and transient systolic dysfunction in adjacent normal myocardium (fractional shortening -38% +/- 34%; P < 0.01). Uniform sustained VT (cycle length 232 +/- 41 msec) was induced in 4 of 6 pigs before ablation, but sustained VT could not be induced afterward. CONCLUSION: Irrigated RF energy produced relatively large lesions in infarcted myocardium without thrombus formation. Changes in tissue thickness and echo density observed with ICE verify irrigated RF lesion delivery. Temporary left ventricular dysfunction is consistently observed in the normal myocardium adjacent to the linear lesion.

Animals↗
PubMed1999

Electroanatomic left ventricular mapping in the porcine model of healed anterior myocardial infarction. Correlation with intracardiac echocardiography and pathological analysis.

BACKGROUND: Catheter ablation for ventricular tachycardia in healed infarction is limited to patients with inducible, tolerated arrhythmias. Strategies that would allow mapping during sinus rhythm might obviate this limitation. METHODS AND RESULTS: Two sets of experiments were performed in adult pigs to refine a new technique for left ventricular mapping. First, detailed endocardial maps were done in 5 normal pigs and 7 pigs 6 to 10 weeks after left anterior descending coronary artery infarction to characterize electrograms in normal and infarcted tissue by electroanatomic mapping (CARTO, Biosense). Electrogram recording sites were verified by intracardiac echo (ICE, 9 MHz) and grouped by location: infarct (area of akinesis by ICE), border (0.5-cm perimeter of akinetic area), and remote. Compared with remote sites, electrograms from infarct sites had smaller amplitudes (1.2+/-0.5 versus 5.1+/-2.1 mV, P<0.001), longer durations (74.2+/-26.3 versus 36.3+/-6.4 ms, P<0.001), and more frequent notched or late components. Border zone electrograms were intermediate in amplitude and duration. Second, infarct characterization by electroanatomic mapping was compared with pathological (exclusion of triphenyltetrazolium chloride staining) and ICE measurements. Infarct size by pathology correlated with the area defined by contiguous electrograms with amplitude </=1 mV (r=0.98, P=0.0001). Infarct size by ICE imaging correlated with the area defined by contiguous electrograms with amplitude </=2 mV (r=0.95, P=0.0016). CONCLUSIONS: Electroanatomic mapping during sinus rhythm allows accurate 3D characterization of infarct architecture and defines the relationship of electrophysiological and anatomic abnormalities. This technique may prove useful in devising anatomically based strategies for ablation of ventricular tachycardia.

Animals↗
PubMed1998

Recording of pacing stimulus artifacts by endovascular defibrillation lead systems: comparison of true and integrated bipolar circuits.

BACKGROUND: The occurrence ICD undersensing of ventricular fibrillation due to the presence of a pacing stimulus artifact (PSA) is in part related to the amplitude of the artifact recorded on the ICD rate sensing circuit. There is little comparative data regarding PSA amplitude recorded by commercial ICD rate-sensing circuits. PURPOSE: To compare PSA amplitude recorded by commercial endovascular defibrillation leads utilizing integrated or true bipolar sensing circuits. METHODS: Nineteen large (60-120 kg) pigs were utilized. Two different commercial endovascular defibrillation leads were evaluated, each with its distal tip located at the right ventricular apex: (1) Medtronic Transvene; and (2) CPI Endotak. Three different rate-sensing circuits were evaluated: (1) Transvene true bipolar (tip-ring); (2) Transvene integrated bipolar (tip-coil); and (3) Endotak integrated bipolar (tip-coil). Using a separate pacing lead located at the left ventricular apex (n = 19 animals) or right ventricular outflow tract (n = 10 animals), pacing was performed at a pulse width of 0.5 milliseconds at outputs of 1.5, 5 and 10 volts. PSA amplitude was recorded at each output by each circuit. RESULTS: During pacing from the left ventricular apex, at each pacing output voltage the PSA amplitude recorded by the true bipolar circuit (0.6 +/- 0.1 mV at 1.5 volts, 2.0 +/- 0.5 mV at 5 volts, 3.7 +/- 0.8 mV at 10 volts) was significantly smaller than recorded by the Transvene integrated circuit (1.4 +/- 0.3 mV at 1.5 volts, 3.8 +/- 0.7 mV at 5 volts, 4.1 +/- 0.8 mV at 10 volts) or the Endotak integrated circuit (1.8 +/- 0.4 mV at 1.5 volts, 4.2 +/- 1.0 mV at 5 volts, 6.3 +/- 1.8 mV at 10 volts). During pacing from the right ventricular outflow tract, at each pacing output voltage the PSA amplitude recorded by the true bipolar circuit (0.7 +/- 0.1 mV at 1.5 volts, 1.7 +/- 0.4 mV at 5 volts, 4.0 +/- 0.7 mV at 10 volts) was significantly smaller than recorded by the Transvene integrated circuit (1.1 +/- 0.4 mV at 1.5 volts, 3.9 +/- 1.2 mV at 5 volts, 7.5 +/- 1.8 mV at 10 volts) or the Endotak integrated circuit (1.6 +/- 0.7 mV at 1.5 volts, 4.3 +/- 1.7 mV at 5 volts, 7.5 +/- 2.6 mV at 10 volts). For both pacing sites, the PSA amplitude recorded by the two integrated circuits was not significantly different. CONCLUSIONS: For a given pacing output voltage, PSA amplitude recorded by commercial endovascular rate sensing/defibrillation leads is greater when the sensing circuit is integrated than when it is true bipolar. These data may be helpful in planning ICD implantation in patients with previously implanted permanent pacemakers.

Animals↗
PubMed1998

A long-lasting interferon-gamma response is induced to a single inoculation of antigen-pulsed dendritic cells.

Vaccines against infectious organisms must produce not only long-lasting immunity but also the appropriate immune response to clear the infection. Obligate intracellular parasites, such as mycobacteria, require a predominantly cell-mediated immune response rather than antibody. Presentation of antigen by dendritic cells (DC) has been associated with the development of strong cell-mediated responses generating the production of interferon-gamma (IFN-gamma). This cytokine has an essential role in the elimination of mycobacteria. Therefore, we investigated both the duration and the nature of the immune response after priming with DC pulsed with mycobacterial antigen and compared this with priming using a conventional adjuvant. We used two strains of mice: C57BL/6, which inherently produces a T-helper 1 (Th1)-type response to mycobacterial antigen, and BALB/c, which does not. DC-enriched cell suspensions, purified DC or cultured bone marrow cells resembling DC (BMAPC) were prepared, pulsed overnight with PPD and injected intravenously (i.v.) into naive mice. Six and 12 weeks later, splenic T lymphocytes from these mice were challenged in vitro with antigen and their proliferative response and cytokine production was determined. Significant antigen-specific proliferation was observed in all assays on rechallenge with antigen in vitro 6 and 12 weeks after the initial priming with DC. IFN-gamma was detected in both strains but was only antigen specific in the C57BL/6 strain. Purified protein derivative (PPD)-pulsed BMAPC generated similar responses 6 weeks after priming. Thus, long-term T-lymphocyte responses and the production of IFN-gamma can be generated using a single inoculation of PPD-pulsed DC.

Animals↗
PubMed1998

Progressive depolarization: a unified hypothesis for defibrillation and fibrillation induction by shocks.

Experimental studies of defibrillation have burgeoned since the introduction of the upper limit of vulnerability (ULV) hypothesis for defibrillation. Much of this progress is due to the valuable work carried out in pursuit of this hypothesis. The ULV hypothesis presented a unified electrophysiologic scheme for linking the processes of defibrillation and shock-induced fibrillation. In addition to its scientific ramifications, this work also raised the possibility of simpler and safer means for clinical defibrillation threshold testing. Recent results from an optical mapping study of defibrillation suggest, however, that the experimental data supporting the ULV hypothesis could instead be interpreted in a manner consistent with traditional views of defibrillation such as the critical mass hypothesis. This review will describe the evidence calling for such a reinterpretation. In one regard the ULV hypothesis superseded the critical mass hypothesis by linking the defibrillation and shock-induced fibrillation processes. Therefore, this review also will discuss the rationale for developing a new defibrillation hypothesis. This new hypothesis, progressive depolarization, uses traditional defibrillation concepts to cover the same ground as the ULV hypothesis in mechanistically unifying defibrillation and shock-induced fibrillation. It does so in a manner consistent with experimental data supporting the ULV hypothesis but which also takes advantage of what has been learned from optical studies of defibrillation. This review will briefly describe how this new hypothesis relates to other contemporary viewpoints and related experimental results.

Animals↗
PubMed1997

Lower frequency (5 MHZ) intracardiac echocardiography in a large swine model: imaging views and research applications.

Our previous investigation indicated that, in the 50-114-kg weight range, the swine model provides transeosophageal echocardiographic normal values for cardiac structures comparable to those found in human adults. Intracardiac echocardiographic imaging using a 12.5-MHz ultrasound catheter is limited, due to ultrasonic attenuation. Transesophageal echocardiographic imaging of the right heart is also limited with its anterior anatomic location. To further study the utility of intracardiac imaging, we placed a 5-MHz (30 Fr) multiplane transducer at the junction of the superior vena cava and right atrium, in the right atrium and right ventricle in 8 closed-chest swine (weight 129 +/- 61 kg). In each animal, complete whole heart imaging was obtained, with tomographic views including the cardiac 4-chamber, right atrium, right ventricle and outflow, left atrium and ventricle, and basal great vessels. Major intracardiac anatomic landmarks (i.e., crista terminalis, right atrial appendage, coronary sinus orifice, interatrial septum, tricuspid valve, right ventricular outflow, pulmonary veins, mitral valve and left ventricular papillary muscles) were visualized in every swine. Thus, this 5-MHz multiplane transducer, as a prototype for a steerable low-frequency intracardiac ultrasound catheter, improved both whole heart and individual cardiac structure imaging from a single intracardiac location. Further technological development and refinement is needed for routine use in research and clinical imaging practice.

Animals↗
PubMed1997

Characterization of the excitable gap in human type I atrial flutter.

OBJECTIVES: We sought to characterize the excitable gap of the reentrant circuit in atrial flutter. BACKGROUND: The electrophysiologic substrate of typical atrial flutter has not been well characterized. Specifically, it is not known whether the properties of the tricuspid valve isthmus differ from those of the remainder of the circuit. METHODS: Resetting was performed from two sites within the circuit: proximal (site A) and distal (site B) to the isthmus in 14 patients with type I atrial flutter. Resetting response patterns and the location where interval-dependent conduction slowing occurred were assessed. RESULTS: Some duration of a flat resetting response (mean +/- SD 40.1 +/- 20.9 ms, 16 +/- 8% of the cycle length) was observed in 13 of 14 patients; 1 patient had a purely increasing response. During the increasing portion of the resetting curve, interval-dependent conduction delay most commonly occurred in the isthmus. In most cases, the resetting response was similar at both sites. In three patients, the resetting response differed significantly between the two sites; this finding suggests that paced beats may transiently change conduction within the circuit or the circuit path, or both. CONCLUSIONS: Some duration of a flat resetting response was observed in most cases of type I atrial flutter, signifying a fully excitable gap in all portions of the circuit. The isthmus represents the portion of the circuit most vulnerable to interval-dependent conduction delay at short coupling intervals.

Action Potentials↗
PubMed1997

Priming to mycobacterial antigen in vivo using antigen-pulsed antigen presenting cells generated in vitro is influenced by the dose and presence of IL-4 in APC cultures.

Antigen presenting cells (APC) similar to immature dendritic cells can be generated in vitro from bone marrow precursors. The authors have compared the yield, the phenotype and the function of murine bone marrow cells cultured for 7 or 11 days in either granulocyte macrophage colony stimulating factor alone (GM BMAPC) or in combination with interleukin-4 (GM/IL-4 BMAPC). The results showed that GM/IL-4 BMAPC expressed the highest levels of MHC Class 2 molecules, CD86/B7-2 and CD80/B7-1 co-stimulatory molecules and the lowest levels of F4/80 macrophage marker. However, when these APC were pulsed with BCG culture filtrate antigen or PPD they were not correspondingly more effective at stimulating activated T lymphocytes in vitro or priming naive T lymphocytes in vivo. Also, in contrast to GM BMAPC, high backgrounds recorded following injections of GM/IL-4 BMAPC without antigen were not consistently reduced by lowering the dose and irradiating the cells prior to administration. The authors conclude that the degree of maturity of BMAPC varies with culture conditions and that this may be an important consideration where BMAPC are to be used in vivo in immunotherapeutic regimens.

Animals↗
PubMed1997

Prospective analysis of genital ulcer disease in Brooklyn, New York.

We prospectively studied 82 men and women with first episodes of genital ulceration. By using newer diagnostic techniques, a definite microbial etiology of 84 infections in 65 of the 82 patients evaluated was found. There were 33 cases of definite primary syphilis, 27 of definite chancroid, and 24 of definite genital herpes simplex. Conclusive evidence of more than one microbial etiology was found for 19 (23%) of the patients. Simultaneous primary syphilis and chancroid was the third most common ulcer infection. This finding underscores the need for both clinical suspicion of multiple infections in patients with genital ulcers and comprehensive testing for all suspicious etiologies.

Adolescent↗
PubMed1997

Low-energy impedance-compensating biphasic waveforms terminate ventricular fibrillation at high rates in victims of out-of-hospital cardiac arrest. LIFE Investigators.

INTRODUCTION: New automatic external defibrillators (AEDs), which are smaller, lighter, easier to use, and less costly make the goal of widespread AED deployment and early defibrillation for out-of-hospital cardiac arrest feasible. The objective of this study was to observe the performance of a low-energy impedance-compensating biphasic waveform in the out-of-hospital setting on 100 consecutive victims of sudden cardiac arrest. METHODS AND RESULTS: AEDs incorporating a 150-J impedance-compensating biphasic waveform were used by 12 EMS systems. Data were obtained from the AED PC card reporting system. Defibrillation was defined as conversion to an organized rhythm or to asystole. Endpoints included: defibrillation efficacy for ventricular fibrillation (VF); restoration of an organized rhythm at the time of patient transfer to an advanced life support (ALS) team or to the emergency department (ED); and time from AED power-on to first defibrillation. The AED correctly identified 44 of 100 patients presenting in VF as requiring a shock (100% sensitivity) and 56 of 100 patients not in VF as not requiring a shock (100% specificity). The time from 911 call to first shock delivery averaged 8.1 +/- 3.0 minutes. A single 150-J biphasic shock defibrillated the initial VF episode in 39 of 44 (89%) patients. The average time from power-on to first defibrillation was 25 +/- 17 seconds. At patient transfer to ALS or ED care, an organized rhythm was present in 34 of 44 (77%) patients presenting with VF. Asystole was present in 7 (16%) and VF in 3 (7%). CONCLUSIONS: Low-energy impedance-compensating biphasic waveforms terminate long-duration VF at high rates in out-of-hospital cardiac arrest. Use of this waveform allows AED device characteristics consistent with widespread AED deployment and early defibrillation.

Adult↗
PubMed1996

Conduction block in the inferior vena caval-tricuspid valve isthmus: association with outcome of radiofrequency ablation of type I atrial flutter.

OBJECTIVES: We sought to 1) correlate conduction block in the isthmus of the right atrium between the inferior vena cava and the tricuspid annulus with the efficacy of catheter ablation of type I atrial flutter, and 2) characterize the effects of ablative lesions on the properties of isthmus conduction. BACKGROUND: There are few data on the mechanism of persistent suppression of recurrence of atrial flutter by catheter ablation. METHODS: Thirty-five patients with type I atrial flutter underwent catheter mapping and ablation. Radiofrequency lesions were applied in the isthmus. Transisthmus conduction before and after the lesions was assessed during atrial pacing in sinus rhythm from the medial and lateral margins of the isthmus at cycle lengths of 600, 400 and 300 ms and the native flutter cycle length. Isthmus conduction block was defined using multipolar recording techniques. There were three treatment groups: group 1 = radiofrequency energy applied during flutter, until termination (n = 14); group 2 = radiofrequency energy applied during atrial pacing in sinus rhythm from the proximal coronary sinus at a cycle length of 600 ms, until isthmus conduction block was observed (n = 14); and group 3 = radiofrequency energy applied until an initial flutter termination, after which further energy was applied during atrial pacing in sinus rhythm until isthmus conduction block was observed (n = 7). RESULTS: In group 1, after the initial flutter termination, isthmus conduction block was observed in 9 of the 14 patients. In each of these nine patients, flutter could not be reinitiated. In each of the remaining five patients, after the initial flutter termination, isthmus conduction was intact and atrial flutter could be reinitiated. Ultimately, successful ablation in each of these patients was also associated with isthmus conduction block. In groups 2 and 3, isthmus conduction block was achieved during radiofrequency energy application, and flutter could not subsequently be reinitiated. Before achieving conduction block, marked conduction slowing or intermittent block, or both, was observed in some patients. In some patients, isthmus conduction block was pacing rate dependent. In addition, recovery from conduction block was common in the laboratory and had a variable time course. At a mean follow-up interval of 10 months (range 1 to 21), the actuarial incidence of freedom from type I flutter was 80% (recurrence in three patients at 7 to 15 months). CONCLUSIONS: Isthmus conduction block is associated with flutter ablation success. Conduction slowing or intermittent block, or both, in the isthmus can occur before achieving persistent block. Recovery of conduction after achieving block is common. Follow-up has revealed a low rate of flutter recurrence after achieving isthmus conduction block, whether the block was achieved in conjunction with termination of flutter.

Adult↗
PubMed1996

Effects of high and low shock energies on sinus electrograms recorded via integrated and true bipolar nonthoracotomy lead systems.

INTRODUCTION: The purpose of this investigation was to prospectively evaluate the voltage- and time-dependent characteristics of a biphasic defibrillator discharge on the amplitude of the rate sensing electrogram recorded from two "integrated" and one true bipolar nonthoracotomy lead system. Prolongation of redetection time has been noted after a failed first shock with nonthoracotomy lead systems. However, a prospective evaluation of the time- and voltage-dependent effects of biphasic shocks on electrogram amplitude with clinically utilized lead systems has not been systematically performed. METHODS AND RESULTS: Five- then 30-J R wave synchronous biphasic discharges were delivered during the supraventricular rhythm through three nonthoracotomy lead systems (Medtronic Transvene, Ventritex TVL, and CPI Endotak C 60 Series). The R wave amplitude was measured immediately postshock and for up to 1 minute. Amplitude changes were compared with preshock baseline value. A 5-J discharge had minimal effect on the R wave amplitude recorded from the three lead systems; however, 30 J resulted in significant diminution in R wave amplitude recorded from the integrated bipolar leads (in the Endotak lead to a greater extent than the TVL lead) with minimal effects on the Transvene lead. Following a 30-J discharge, the time constant for R wave recovery was 4.2, 14.9, and 15.3 seconds for Transvene, TVL, and Endotak 60 leads, respectively. CONCLUSION: There are voltage- and time-dependent reductions in postshock R wave amplitude. Integrated bipolar systems appear more affected than the "true" bipolar lead evaluated. This may be due, in part, to lead design, distance of distal defibrillating surface from rate sensing cathode, and the incorporation of the defibrillating surface as the rate sensing anode. The influence of post-shock R wave diminution on subsequent redetection remains speculative but may have implications for subsequent lead development.

Adult↗
PubMed1996

Shock-induced depolarization of refractory myocardium prevents wave-front propagation in defibrillation.

The elimination of most, if not all, propagating wave fronts of electrical activation by a shock constitutes a minimum prerequisite for successful defibrillation. However, the factors responsible for the prevention of postshock propagating activity are unknown. We investigated the determinants of this effect of defibrillation shocks in 23 Langendorff-perfused rabbit hearts by optically mapping cardiac cellular electrical activity by means of laser scanning. The optical action potentials obtained by this method were continuously recorded from 100 ventricular epicardial sites before, during, and after shock delivery during fibrillation. Analysis of activation maps showed that postshock propagating activity arose from areas depolarized by the shock. In 273 shock episodes, 898 sites at the border of shock-depolarized areas (BSDAs) from which wave-front propagation could have arisen were identified. The incidence of postshock propagation from BSDA sites was inversely related to refractoriness, as indexed by coupling interval (CI) or the optical takeoff potential (Vm). Specifically, there was a near-zero probability of postshock propagation if the shock caused depolarization at CIs < 50% of the fibrillation cycle length or from myocardium still depolarized to > or = 60% of the amplitude of a paced action potential (APA). Furthermore, incidences of wave-front propagation following shocks were consistently lower than the propagation incidences of naturally occurring unshocked fibrillation wave fronts, at comparable CIs and Vms. We conclude that the incidence of postshock wave-front propagation decreases with increasing refractoriness at the BSDA and that shock-induced depolarization of effectively refractory myocardium (ie, depolarized to > or = 60% APA) is required to guarantee the cessation of continued wave-front propagation in defibrillation.

Animals↗
PubMed1995

Electrophysiological effects of flecainide on anisotropic conduction and reentry in infarcted canine hearts.

BACKGROUND: The class IC antiarrhythmic drug flecainide has been shown to be ineffective for the treatment of ventricular arrhythmias in some patients who have had a prior myocardial infarction and sometimes even provoke arrhythmias (proarrhythmic effect). Since some ventricular tachycardias may be caused by anisotropic reentry, we determined the effects of flecainide on this mechanism for reentry in infarcted canine hearts in order to determine possible causes for its clinical effects. METHODS AND RESULTS: The effects of flecainide were determined on ventricular tachycardia induced by programmed electrical stimulation in dogs with healing myocardial infarction 4 days after coronary artery occlusion. Activation in the reentrant circuits causing tachycardia was mapped with a 196-channel computerized mapping system. We found that flecainide converted inducible unsustained ventricular tachycardia to inducible sustained ventricular tachycardia by modifying conduction in the reentrant circuit. In general, by slowing conduction, the reentrant wave front did not block after flecainide, leading to perpetuation of reentrant excitation. When sustained ventricular tachycardia could be induced before the drug, flecainide prolonged the coupling interval of premature impulses necessary to induce tachycardia by lengthening the line of block and slowing conduction around it. Flecainide also slowed the rate of the tachycardia but did not terminate it. The anisotropic reentrant circuits were modified so that the central common pathway of "figure-of-eight" circuits was narrowed and lengthened due to extension of the lines of block that bounded the pathways. Extension of the lines of block resulted from depression of conduction in the direction transverse to the long axis of the myocardial fiber bundles caused by flecainide. Flecainide also slowed conduction in the longitudinal direction in part of the circuits. The depressant effects of flecainide on both longitudinal and transverse anisotropic conduction were quantified by pacing from the center of the electrode array and it was found, contrary to predictions, that transverse conduction was depressed as much as longitudinal conduction. CONCLUSIONS: Flecainide slows conduction in both the longitudinal and transverse direction relative to the orientation of the myocardial fibers. This enables sustained reentry to occur more easily. Flecainide does not cause conduction block in crucial regions of reentrant circuits (central common pathway) and therefore does not prevent reentrant tachycardia in healing infarcts.

Animals↗
PubMed1995

Animated images of cardiac membrane voltage during defibrillation.

Optical recording using voltage-sensitive dyes has been used to investigate the mechanisms of defibrillation because it (1) is immune to the artifacts produced by high-voltage shocks, (2) provides the time course of the membrane action potential, and (3) can be used to make simultaneous recordings at many sites. The authors used the laser scanning technique to optically record action potentials from 100 sites with 1-ms resolution on the surface of the isolated, perfused rabbit heart during defibrillation. The data were typically analyzed by constructing maps of impulse propagation and examining individual recordings from sites of interest. Described here is a new analysis method that creates millisecond-by-millisecond images of the spatial distribution of membrane potentials. The experimental protocol applied a test shock to the fibrillating heart, followed by a rescue shock and a paced beat. Optical recordings were calibrated to yield membrane voltage as a percentage of the resting and overshoot levels of the postrescue stimulated action potential. The positions of the recording sites and the membrane voltage levels for all 100 sites during a single 1-ms interval were used to interpolate membrane voltage levels at points within a 128 x 128 pixel frame using the biharmonic interpolation method. The level of membrane potential was encoded by pixel color and surface elevation. Sequential frames were viewed as a face-on two dimensional or as a three-dimensional perspective of the colored surface. Animation of membrane voltage distributions enabled the visualization of the interaction between the shock-induced electrophysiologic response and the propagation of electrical activity preceding and following a defibrillation shock. Successful defibrillation shocks synchronized repolarization across the surface of the heart following the shock.

Action Potentials↗