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2.
Eur Heart J ; 23(14): 1131-8, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12090752

ABSTRACT

AIMS: Conduction through separated myocyte bundles causes multipotential electrograms and reentrant ventricular tachycardia. We hypothesized that without initiating tachycardia, the reentry region could be detected by analysing the change in multipotential electrograms during two different activation sequences. METHODS AND RESULTS: During catheter mapping and ablation in 16 patients with ventricular tachycardia late after infarction ventricular electrograms were recorded from 1072 sites during atrial and right ventricular paced ventricular activation. Multipotential electrograms were present during both activation sequences at 285 (27%) sites, during atrial pacing only at 159 (15%) sites and during right ventricular pacing only at 152 (14%) sites. Sites with multipotential electrograms during both activation sequences were more often related to a ventricular tachycardia circuit isthmus (43%) as compared to sites where such electrograms were present during one activation sequence (20%). Multipotential electrograms with >2 low amplitude deflections and a >100 ms difference in duration between the two activation sequences were infrequent but highly predictive of the reentry circuit. CONCLUSION: Regions with fixed multipotentials consistent with conduction block might be useful guides for ablation approaches that target large regions of the infarct, but are not sufficiently specific to be the sole guide for focal ablation approaches.


Subject(s)
Cardiac Pacing, Artificial , Catheter Ablation/methods , Electrocardiography , Myocardial Infarction/complications , Myocardial Infarction/diagnosis , Tachycardia, Atrioventricular Nodal Reentry/etiology , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/therapy , Aged , Echocardiography , Electrophysiology , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Risk Assessment , Sensitivity and Specificity , Tachycardia, Atrioventricular Nodal Reentry/physiopathology , Tachycardia, Ventricular/diagnosis , Treatment Outcome
3.
Circulation ; 104(5): 550-6, 2001 Jul 31.
Article in English | MEDLINE | ID: mdl-11479252

ABSTRACT

BACKGROUND: The purpose of this study was to determine how often accessory atrioventricular (AV) pathways (AP) cross the AV groove obliquely. With an oblique course, the local ventriculoatrial (VA) interval at the site of earliest atrial activation (local-VA) and the local-AV interval at the site of earliest ventricular activation (local-AV) should vary by reversing the direction of the paced ventricular and atrial wavefronts, respectively. METHODS AND RESULTS: One hundred fourteen patients with a single AP were studied. Two ventricular and two atrial pacing sites on opposite sides of the AP were selected to reverse the direction of the ventricular and atrial wavefronts along the annulus. Reversing the ventricular wavefront increased local-VA by >/=15 ms in 91 of 106 (91%) patients. With the shorter local-VA, the ventricular potential overlapped the atrial potential along a 17.2+/-8.5-mm length of the annulus. No overlap occurred with the opposite wavefront. Reversing the atrial wavefront increased local-AV by >/=15 ms in 32 of 44 (73%) patients. With the shorter local-AV, the atrial potential overlapped the ventricular potential along an 11.9+/-8.9-mm length of the annulus. No overlap occurred with the opposite wavefront. Mapping during longer local-VA or local-AV identified an AP potential in 102 of 114 (89%) patients. Catheter ablation eliminated AP conduction in all 111 patients attempted (median, 1 radiofrequency application in 99 patients with an AP potential versus 4.5 applications without an AP potential). CONCLUSIONS: Reversing the direction of the paced ventricular or atrial wavefront reveals an oblique course in most APs and facilitates localization of the AP potential for catheter ablation.


Subject(s)
Atrioventricular Node/physiopathology , Cardiac Pacing, Artificial , Heart Conduction System/physiopathology , Adolescent , Adult , Aged , Catheter Ablation , Child , Child, Preschool , Female , Heart Atria/physiopathology , Heart Ventricles/physiopathology , Humans , Male , Middle Aged
4.
J Cardiovasc Electrophysiol ; 12(5): 592-9, 2001 May.
Article in English | MEDLINE | ID: mdl-11386522

ABSTRACT

INTRODUCTION: Focal paroxysmal atrial fibrillation (AF) was shown recently to originate in the pulmonary veins (PVs) and superior vena cava (SVC). In the present study, we describe an animal model in which local high-frequency electrical stimulation produces focal atrial activation and AF/AT (atrial tachycardia) with electrogram characteristics consistent with clinical reports. METHODS AND RESULTS: In 21 mongrel dogs, local high-frequency electrical stimulation was performed by delivering trains of electrical stimuli (200 Hz, impulse duration 0.1 msec) to the PVs/SVC during atrial refractoriness. Atrial premature depolarizations (APDs), AT, and AF occurred with increasing high-frequency electrical stimulation voltage. APD/AT/AF originated adjacent to the site of high-frequency electrical stimulation and were inducible in 12 of 12 dogs in the SVC and in 8 of 9 dogs in the left superior PV (left inferior PV: 7/8, right superior PV: 6/8; right inferior PV: 4/8). In the PVs, APDs occurred at 13+/-8 V and AT/AF at 15+/-9 V (P < 0.01; n = 25). In the SVC, APDs were elicited at 19+/-6 V and AT/AF at 26+/-6 V (P < 0.01; n = 12). High-frequency electrical stimulation led to local refractory period shortening in the PVs. The response to high-frequency electrical stimulation was blunted or prevented after beta-receptor blockade and abolished by atropine. In vitro, high-frequency electrical stimulation induced a heterogeneous response, with shortening of the action potential in some cells (from 89+/-35 msec to 60+/-22 msec; P < 0.001; n = 7) but lengthening of the action potential and development of early afterdepolar-izations that triggered APD/AT in other cells. Action potential shortening was abolished by atropine. CONCLUSION: High-frequency electrical stimulation evokes rapid ectopic beats from the PV/SVC, which show variable degrees of conduction block to the atria and induce AF, resembling findings in patients with focal idiopathic paroxysmal AF. The occurrence of the arrhythmia in this animal model was likely due to alterations in local autonomic tone by high-frequency electrical stimulation. Further research is needed to prove absolutely that the observed effects of high-frequency electrical stimulation were caused by autonomic nerve stimulation.


Subject(s)
Atrial Fibrillation/physiopathology , Animals , Atrial Premature Complexes/physiopathology , Autonomic Nervous System/physiopathology , Disease Models, Animal , Dogs , Electric Stimulation/instrumentation , Electric Stimulation/methods , Heart Atria/physiopathology , Models, Animal , Pulmonary Veins/physiopathology , Vena Cava, Superior/physiopathology
5.
J Interv Card Electrophysiol ; 5(1): 89-95, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11248780

ABSTRACT

UNLABELLED: Transseptal left heart catheterization has been performed as an alternative to the retrograde approach since 1958. However, this procedure can result in life-threatening complications, some of which may occur because of insufficient anatomical landmarks. Accordingly, we sought to assess the safety and efficacy of a new transseptal left heart catheterization technique designed for ablation procedures. Specifically, we examined whether electrode catheters could be used as anatomical landmarks, permitting identification of the aortic root and other critical structures. RESULTS: One hundred and eight consecutive patients underwent transseptal left heart catheterization under biplane fluoroscopy during catheter ablation. Electrode catheters positioned in the right atrial appendage, His bundle region, and coronary sinus were used as anatomical landmarks to guide the transseptal unit to the fossa ovalis. The angles of the right anterior and left anterior oblique projections were selected in each patient based on the orientation of the His bundle and coronary sinus catheters. Transseptal left heart catheterization was successfully performed in all patients without complications. In contrast to previous reports, the direction of the needle at the successful puncture site in the last 96 patients varied substantially: 2 o'clock in 13 patients (13 %); 3 o'clock in 43 patients (45 %); and 4 o'clock in 40 patients (42 %). CONCLUSION: The use of electrode catheters as anatomical landmarks and biplane fluoroscopy facilitates transseptal catheterization. This approach can be used safely during catheter ablation procedures.


Subject(s)
Cardiac Catheterization/methods , Catheter Ablation , Heart Conduction System/surgery , Adolescent , Adult , Aged , Child , Electrocardiography , Electrodes , Female , Humans , Male , Middle Aged , Prospective Studies
6.
Circulation ; 103(5): 699-709, 2001 Feb 06.
Article in English | MEDLINE | ID: mdl-11156882

ABSTRACT

BACKGROUND: The purpose of this study was to characterize the circuit of macroreentrant right atrial tachycardia (MacroAT) in patients after surgical repair of congenital heart disease (SR-CHD). METHODS AND RESULTS: Sixteen patients with atrial tachycardia (AT) after SR-CHD were studied (atrial septal defect in 6, tetralogy of Fallot in 4, and Fontan procedure in 6). Electroanatomic right atrial maps were obtained during 15 MacroATs in 13 patients, focal AT in 1 patient, and atrial pacing in 2 patients without stable AT. A large area of low bipolar voltage (/=2 scars forming narrow channels. Ablation within the channels eliminates MacroAT.


Subject(s)
Heart Septal Defects, Atrial/surgery , Tachycardia/etiology , Adult , Atrial Flutter , Atrial Function, Right , Catheter Ablation , Electrophysiology , Female , Follow-Up Studies , Fontan Procedure , Heart Septal Defects, Atrial/complications , Heart Septal Defects, Atrial/physiopathology , Humans , Male , Middle Aged , Tachycardia/physiopathology , Tachycardia/surgery
7.
Pacing Clin Electrophysiol ; 24(12): 1765-73, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11817810

ABSTRACT

The 7 Fr "split-tip electrode" (2.5-mm tip electrode divided longitudinally into four electrodes with an adjacent 2-mm ring electrode) improves mapping resolution due to its small recording electrodes and narrow interelectrode distances (0.1 mm). The purpose of this study was to examine the temperature-controlled ablation properties of this electrode. In seven anesthetized dogs, the thigh muscles were exposed and superfused with canine blood. A split-tip catheter electrode (with a thermocouple in each of the five electrodes) and a conventional 4-mm catheter electrode were positioned at constant pressure perpendicular or parallel to the surface of the thigh muscle. Impedance measured between each split electrode and a skin patch correlated with the degree of contact with blood and tissue. In the parallel catheter to tissue orientation, split electrodes not in contact with tissue had a low impedance (mean 210-224 ohms), and the split electrode almost entirely in contact with tissue had the highest impedance (380 +/- 56 ohms). In the perpendicular catheter to tissue orientation all split electrodes had a similar impedance (mean 279-286 ohms). A total of 75 radiofrequency (RF) lesions were produced in the temperature-controlled mode with the 4-mm electrode (target 60 degrees C) or the split-tip electrode (power limited by the hottest electrode reaching 70 degrees C) with current delivered to all five electrodes simultaneously, or only to electrodes in contact with tissue. Lesion depth was not significantly different between electrodes in the parallel orientation (5.2 +/- 0.9 vs 5.1 +/- 1.4 vs 5.3 +/- 1.1 mm), but significantly deeper with the conventional 4-mm tip electrode in the perpendicular orientation (6.7 +/- 1.2 vs 5.3 +/- 1.3 vs 5.6 +/- 0.9 mm, P < 0.05). This was due to higher power delivered to the conventional 4-mm electrode (27 +/- 9 vs 17 +/- 7 vs 15 +/- 7 W, P < 0.05) because convective cooling by the blood flow was less effective for the split-tip electrode due to a reduced heat conduction across the interelectrode space from the hottest electrode to cooler areas of the group of five electrodes (mean temperature difference between the hottest split electrodes and the ring electrode: 24 degrees C). Electrode cooling or heat conduction was not effected by the elimination of current delivery to non-contact electrodes. Steam pops occurred in 36% of applications with the conventional 4-mm electrode in the perpendicular orientation but never with the split-tip electrode in spite of the higher target temperature. Measurement of impedance from the split electrodes allow the determination of electrode tissue contact and RF lesions produced with the split-tip electrode in the temperature-controlled mode using a target of 70 degrees C were of reasonable size and not associated with steam pops.


Subject(s)
Catheter Ablation , Animals , Catheter Ablation/instrumentation , Dogs , Electric Impedance , Electrodes , Equipment Design , Muscle, Skeletal , Temperature
8.
Circulation ; 102(22): 2774-80, 2000 Nov 28.
Article in English | MEDLINE | ID: mdl-11094046

ABSTRACT

BACKGROUND: Vagal stimulation shortens the atrial effective refractory period (AERP) and maintains atrial fibrillation (AF). This study investigated whether the parasympathetic pathways that innervate the atria can be identified and ablated by use of transvenous catheter stimulation and radiofrequency current catheter ablation (RFCA) techniques. METHODS AND RESULTS: In 11 dogs, AERPs were determined at 7 atrial sites during bilateral cervical vagal nerve stimulation (VNS) and electrical stimulation of the third fat pad (20 Hz) in the right pulmonary artery (RPA). VNS shortened the AERP at all sites (from 123+/-4 to 39+/-4 ms, P<0.001) and increased the covariance of AERP (COV-AERP) (from 9+/-3% to 27+/-13%, P<0.001). RPA stimulation shortened the AERP at all sites from 123+/-4 to 66+/-13 ms (P<0.001) and increased the COV-AERP from 9+/-3% to 30+/-12% (P<0.001). In 7 dogs, transvascular RFCA of the parasympathetic pathways along the RPA was performed, and in 3 dogs, additional RFCA of parasympathetic fibers along the inferior (n=2) or superior (n=1) vena cava was performed. RFCA blunted the AERP shortening at all sites during VNS (114+/-4 ms after RFCA), abolished the increase of COV-AERP during VNS (12+/-7% after RFCA), and led to an increase of the baseline AERP (123+/-4 ms before versus 127+/-3 ms after RFCA, P=0.002). Before RFCA, AF could be induced and maintained as long as VNS was continued, whereas after RFCA, AF was no longer inducible during VNS. CONCLUSIONS: -Transvascular atrial parasympathetic nerve system modification by RFCA abolishes vagally mediated AF. This antifibrillatory procedure may provide a foundation for investigating the usefulness of neural ablation in chronic animal models of AF and eventually in patients with AF and high vagal tone.


Subject(s)
Atrial Fibrillation/physiopathology , Autonomic Nervous System/physiopathology , Catheter Ablation , Heart/innervation , Vagus Nerve/physiopathology , Animals , Atrial Fibrillation/surgery , Atrioventricular Node/physiopathology , Dogs , Electric Stimulation , Heart/physiopathology , Heart Atria/pathology , Heart Atria/physiopathology , Heart Conduction System/physiopathology , Parasympathetic Nervous System/physiopathology , Sinoatrial Node/physiopathology
9.
J Cardiovasc Electrophysiol ; 11(1): 64-9, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10695464

ABSTRACT

INTRODUCTION: In previous reports, we demonstrated a technique for parasympathetic nerve stimulation (PNS) within the superior vena cava, pulmonary artery, and coronary sinus to control rapid ventricular rates during atrial fibrillation (AF). In this report, we describe another vascular site, the inferior vena cava (IVC), at which negative dromotropic effects during AF could consistently be obtained. Moreover, stimulation at this site also induced dual AV nodal electrophysiology. METHODS AND RESULTS: PNS was performed in ten dogs using rectangular stimuli (0.1 msec/20 Hz) delivered through a catheter with an expandable electrode basket at its tip. Within 3 minutes and without using fluoroscopy, the catheter was positioned at an effective PNS site in the IVC at the junction of the right atrium. AF was induced and maintained by rapid atrial pacing. During stepwise increase of the PNS voltage from 2 to 34 V, a graded response of ventricular rate slowing during AF was observed (266 +/- 79 msec without PNS vs 1,539 +/- 2,460 msec with PNS at 34 V; P = 0.005 by analysis of variance), which was abolished by atropine and blunted by hexamethonium. In three animals, PNS was performed during sinus rhythm. Dual AV nodal electrophysiology was present in 1 of 3 dogs in control, whereas with PNS, dual AV nodal electrophysiology was observed in all three dogs. PNS did not significantly change sinus rate or arterial blood pressure during ventricular pacing. CONCLUSION: Stable and consistent transvenous electrical stimulation of parasympathetic nerves innervating the AV node can be achieved in the IVC, a transvenous site that is rapidly and readily accessible. The proposed catheter approach for PNS can be used to control ventricular rate during AF in this animal model.


Subject(s)
Atrioventricular Node/physiopathology , Parasympathetic Nervous System/physiopathology , Vena Cava, Inferior/physiopathology , Animals , Atrial Fibrillation/physiopathology , Blood Pressure , Cardiac Pacing, Artificial , Dogs , Electric Stimulation/methods , Electrocardiography , Heart Rate , Veins , Ventricular Function
10.
J Interv Card Electrophysiol ; 4(1): 219-24, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10729837

ABSTRACT

We previously showed that parasympathetic stimulation by a basket electrode catheter (BEC) positioned in the superior vena cava (SVC) can slow sinus rate (SR) or ventricular response (VR) during atrial fibrillation (AF). In 11 dogs, anesthetized with Na-pentobarbital, standard ECG leads II and aVR, blood pressure and right atrial electrograms were continuously monitored. Two different BEC configurations (B1, B2) were tested in the SVC. B1 consisted of five metal splines, each 3 cm in length. Stimulation was applied between adjacent splines. B2 consisted of 2 electrodes at opposite ends of each of 5 splines and a larger electrode at the middle of each spline. Stimulation was delivered between the two end electrodes and the middle electrode on the same arm. Stimulation consisted of square wave stimuli, each 0.1 msec duration, frequency 20 Hz at voltages from 1-40 V. Six dogs were studied with B1 and five were studied with the B2 configuration. The average voltage required to produce a 50% decrease in heart rate was 22+/- 12 V when stimulating between adjacent splines (B1) compared to 10+/- 5 V when stimulating along a single spline (B2), a 55% decrease (p

Subject(s)
Atrial Fibrillation/physiopathology , Catheterization , Electric Stimulation , Heart Rate , Heart/innervation , Parasympathetic Nervous System/physiology , Animals , Dogs , Equipment Design , Humans , Infant, Newborn , Vena Cava, Superior
11.
Dev Biol ; 220(1): 16-26, 2000 Apr 01.
Article in English | MEDLINE | ID: mdl-10720427

ABSTRACT

The vertebrate embryonic hindbrain is segmented into rhombomeres. Gene expression studies suggest that amphioxus, the closest invertebrate relative of vertebrates, has a hindbrain homolog. However, this region is not overtly segmented in amphioxus, raising the question of how hindbrain segmentation arose in chordate evolution. Vertebrate hindbrain segmentation includes the patterning of cranial motor neurons, which can be identified by their expression of the LIM-homeodomain transcription factor islet1. To learn if the amphioxus hindbrain homolog is cryptically segmented, we cloned an amphioxus gene closely related to islet1, which we named simply islet. We report that amphioxus islet expression includes a domain of segmentally arranged cells in the ventral hindbrain homolog. We hypothesize that these cells are developing motor neurons and reveal a form of hindbrain segmentation in amphioxus. Hence, vertebrate rhombomeres may derive from a cryptically segmented brain present in the amphioxus/vertebrate ancestor. Other islet expression domains provide evidence for amphioxus homologs of the pineal gland, adenohypophysis, and endocrine pancreas. Surprisingly, homologs of vertebrate islet1-expressing spinal motor neurons and Rohon-Beard sensory neurons appear to be absent.


Subject(s)
Chordata, Nonvertebrate/embryology , Chordata, Nonvertebrate/genetics , Homeodomain Proteins/genetics , Nerve Tissue Proteins/genetics , Rhombencephalon/embryology , Amino Acid Sequence , Animals , Base Sequence , Body Patterning/genetics , Chordata, Nonvertebrate/metabolism , DNA, Complementary/genetics , Evolution, Molecular , Female , Gene Expression Regulation, Developmental , In Situ Hybridization , LIM-Homeodomain Proteins , Male , Molecular Sequence Data , Motor Neurons/cytology , Phylogeny , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rhombencephalon/cytology , Rhombencephalon/metabolism , Tissue Distribution , Transcription Factors
12.
J Am Coll Cardiol ; 34(7): 2043-50, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10588222

ABSTRACT

OBJECTIVES: To identify intravascular sites for continuous, stable parasympathetic stimulation (PS) in order to control the ventricular rate during atrial fibrillation (AF). BACKGROUND: Ventricular rate control during AF in patients with congestive heart failure is a significant clinical problem because many drugs that slow the ventricular rate may depress ventricular function and cause hypotension. Parasympathetic stimulation can exert negative dromotropic effects without significantly affecting the ventricles. METHODS: In 22 dogs, PS was performed using rectangular stimuli (0.05 ms duration, 20 Hz) delivered through a catheter with an expandable electrode-basket at its end. The catheter was positioned either in the superior vena cava (SVC, n = 6), coronary sinus (CS, n = 10) or right pulmonary artery (RPA, n = 6). The basket was then expanded to obtain long-term catheter stability. Atrial fibrillation was induced and maintained by rapid atrial pacing. RESULTS: Nonfluoroscopic (SVC) and fluoroscopic (CS/RPA) identification of effective intravascular PS sites was achieved within 3 to 10 min. The ventricular rate slowing effect during AF started and ceased immediately after on-offset of PS, respectively, and could be maintained over 20 h. In the SVC, at least a 50% increase of ventricular rate (R-R) intervals occurred at 22 +/- 11 V (331 +/- 139 ms to 653 +/- 286 ms, p < 0.001), in the CS at 16 +/- 10 V (312 +/- 102 ms vs. 561 +/- 172 ms, p < 0.001) and in the RPA at 18 +/- 7 V (307 +/- 62 ms to 681 +/- 151 ms, p < 0.001). Parasympathetic stimulation did not change ventricular refractory periods. CONCLUSIONS: Intravascular PS results in a significant ventricular rate slowing during AF in dogs. This may be beneficial in patients with AF and rapid ventricular response since many drugs that decrease atrioventricular conduction have negative inotropic effects which could worsen concomitant congestive heart failure.


Subject(s)
Atrial Fibrillation/physiopathology , Ganglia, Parasympathetic/physiopathology , Heart Rate/physiology , Heart Ventricles/physiopathology , Animals , Atrial Fibrillation/diagnosis , Atropine , Catheterization, Central Venous , Catheterization, Peripheral , Cervical Plexus/drug effects , Cervical Plexus/surgery , Dogs , Electric Stimulation , Electrocardiography , Heart Ventricles/innervation , Parasympathectomy , Parasympatholytics , Pericardium/innervation , Pulmonary Artery , Vena Cava, Superior
13.
J Cardiovasc Electrophysiol ; 10(11): 1517-24, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10571371

ABSTRACT

INTRODUCTION: Epicardial electrical stimulation of parasympathetic nerves innervating the sinus node has been shown to decrease sinus rate. We investigated whether intravascular parasympathetic cardiac nerve stimulation (IPS) can be achieved over a relatively long-term period to slow the supraventricular rate. METHODS AND RESULTS: Fifteen dogs were investigated. IPS was performed with rectangular stimuli (0.05-msec duration, 20 Hz) using a catheter with an expandable electrode basket. The catheter was positioned in the superior vena cava (SVC; n = 9) or right pulmonary artery (RPA; n = 6). The basket then was expanded to hold the catheter in place. Nonfluoroscopic identification of effective IPS sites was achieved within 5 minutes in the SVC. Increasing IPS voltage resulted in a graded response of supraventricular rate slowing. A 50% prolongation of the baseline atrial cycle length was achieved with 28 V in the SVC (1,056 +/- 355 msec vs 489 +/- 154 msec; P < 0.001) and 25 V in the RPA (1,181 +/- 306 msec vs 518 +/- 138 msec; P < 0.01). The rate slowing started immediately after IPS onset, terminated abruptly after IPS cessation, and could be maintained over 10 hours. A rate slowing effect also was observed when the sinus rate was increased by isoproterenol (SVC: 304 +/- 8 msec/RPA: 341 +/- 9 msec with isoproterenol vs SVC: 635 +/- 12 msec with isoproterenol + IPS at 39 V/ RPA: 584 +/- 16 msec with isoproterenol + IPS at 38 V; n = 6). CONCLUSION: IPS results in a significant supraventricular rate slowing that is stable over a relatively long period and may be applied to slow undesirable sinus tachycardia in acute ischemic syndromes or to counteract undesirable chronotropic effects of catecholamines during treatment of cardiogenic or septic shock and acute congestive heart failure.


Subject(s)
Electric Stimulation Therapy , Electric Stimulation Therapy/methods , Heart Conduction System/physiology , Heart Rate/physiology , Parasympathetic Nervous System/physiology , Animals , Catheterization , Dogs , Electric Stimulation Therapy/instrumentation , Fluoroscopy , Jugular Veins , Pulmonary Artery/diagnostic imaging , Time Factors , Vena Cava, Superior/diagnostic imaging , Vena Cava, Superior/physiology
14.
Vaccine ; 17(7-8): 660-8, 1999 Feb 26.
Article in English | MEDLINE | ID: mdl-10067671

ABSTRACT

There is currently no commercially available vaccine for Epstein Barr virus (EBV)-related disease in humans. Since the EBV glycoprotein gp350/220 is the primary target for EBV-neutralizing antibodies following natural infection in humans and some forms of gp350/220 have been shown to protect against EBV-related disease in animal models, it is a likely candidate for an EBV subunit vaccine. We have made gp350/220 gene constructs that facilitate gp350 secretion from CHO cells and created splice site mutations in the gene that effectively prevent production of the gp220 species. Recombinant CHO cell gp350 (MSTOP gp350) is recognized by several different anti-gp350/220 monoclonal antibodies, and is also competent to bind to the cellular EBV receptor, CD21, suggesting that the recombinant protein is conformationally similar to wild-type EBV gp350/220. The MSTOP gp350 antigen raises high antibody titers in rabbits and these antibodies neutralize wild-type EBV. These properties make MSTOP gp350 a realistic candidate for a subunit vaccine against EBV-related disease.


Subject(s)
Herpesvirus 4, Human/immunology , Vaccines, DNA/genetics , Viral Matrix Proteins/genetics , Viral Matrix Proteins/immunology , Viral Vaccines/biosynthesis , Viral Vaccines/genetics , Animals , Antibodies, Viral/biosynthesis , Antibodies, Viral/blood , CHO Cells , Cricetinae , Genetic Vectors/immunology , Herpesvirus 4, Human/genetics , Humans , Neutralization Tests , Plasmids/genetics , Rabbits , Transfection , Vaccines, DNA/biosynthesis , Vaccines, DNA/immunology , Viral Matrix Proteins/biosynthesis , Viral Vaccines/immunology
15.
J Electrocardiol ; 32 Suppl: 16-21, 1999.
Article in English | MEDLINE | ID: mdl-10688298

ABSTRACT

The purpose of this study was to utilize a 3-dimensional (3D) electroanatomical mapping system (CARTO) to characterize the reentrant circuit in macroreentrant right atrial tachycardia (AT) following right atriotomy. Right atrial mapping was performed during incessant AT in a patient who had a right atriotomy for closure of an atrial septal defect. During AT, the right atrial free wall exhibited a large contiguous area of low bipolar voltage (< or =0.5 mV, 7.3 cm in length, and 6.3 cm in width). Two discrete scars, showing no electrical potential, were identified within the large low-voltage area. A larger vertical scar (thought to be from the atriotomy) and a smaller second scar (possible inferior vena cava cannulation scar) formed a narrow channel (1.5 cm in width) between these 2 scars. Right atrial activation propagated around the large upper scar, and then propagated through the channel between the 2 scars. A single application of radiofrequency current within the channel eliminated the macroreentrant AT. In conclusion, macroreentrant AT following right atriotomy was associated with 2 discrete scars and utilized the isolated channel between the 2 scars. Ablation within the channel effectively eliminated macroreentrant AT after atriotomy and eliminated the requirement for linear ablation between one or more of the scars and the tricuspid annulus.


Subject(s)
Body Surface Potential Mapping/instrumentation , Catheter Ablation/instrumentation , Electrocardiography/instrumentation , Heart Atria/surgery , Image Processing, Computer-Assisted/instrumentation , Postoperative Complications/surgery , Tachycardia, Atrioventricular Nodal Reentry/physiopathology , Tachycardia, Atrioventricular Nodal Reentry/surgery , Cardiac Pacing, Artificial , Cicatrix/physiopathology , Cicatrix/surgery , Heart Atria/physiopathology , Humans , Postoperative Complications/physiopathology , Signal Processing, Computer-Assisted/instrumentation
16.
Dev Genes Evol ; 208(10): 569-77, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9811975

ABSTRACT

Homologs of the Drosophila snail gene have been characterized in several vertebrates. In addition to being expressed in mesoderm during gastrulation, vertebrate snail genes are also expressed in presumptive neural crest and/or its derivatives. Given that neural crest is unique to vertebrates and is considered to be of fundamental importance in their evolution, we have cloned and characterized the expression of a snail gene from amphioxus, a cephalochordate widely accepted as the sister group of the vertebrates. We show that, at the amino acid sequence level, the amphioxus snail gene is a clear phylogenetic outgroup to all the characterized vertebrate snail genes. During embryogenesis snail expression initially becomes restricted to the paraxial or presomitic mesoderm of amphioxus. Later, snail is expressed at high levels in the lateral neural plate, where it persists during neurulation. Our results indicate that an ancestral function of snail genes in the lineage leading to vertebrates is to define the paraxial mesoderm. Furthermore, our results indicate that a cell population homologous to the vertebrate neural crest may be present in amphioxus, thus providing an important link in the evolution of this key vertebrate tissue.


Subject(s)
Chordata, Nonvertebrate/embryology , Chordata, Nonvertebrate/genetics , DNA-Binding Proteins/genetics , Transcription Factors/genetics , Amino Acid Sequence , Animals , DNA, Complementary/genetics , Evolution, Molecular , Gene Expression Regulation, Developmental , In Situ Hybridization , Mesoderm/metabolism , Molecular Sequence Data , Neural Crest/metabolism , Phylogeny , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Homology, Amino Acid , Snail Family Transcription Factors
17.
Circulation ; 98(17): 1790-5, 1998 Oct 27.
Article in English | MEDLINE | ID: mdl-9788835

ABSTRACT

BACKGROUND: The purpose of this study was to determine whether the coronary sinus (CS) musculature has electrical connections to the right atrium (RA) and left atrium (LA) and forms an RA-LA connection. METHODS AND RESULTS: Six excised dog hearts were perfused in a Langendorff preparation. A 20-electrode catheter (2-4-2-mm spacing center to center) was placed along the CS. Excision of the pulmonary veins provided access to the LA, and a second 20-electrode catheter was placed along the LA endocardium opposite the CS catheter. An incision opened the CS longitudinally, and microelectrodes were inserted into the CS musculature and adjacent LA myocardium. Continuous CS musculature was visible along a 35+/-9-mm length of the CS beginning at the ostium. During lateral LA pacing, CS electrodes recorded double potentials, a rounded, low-frequency potential followed by a sharp potential. The rounded initial potential propagated in the lateral-to-septal direction and represented "far-field" LA activation (timing coincided with adjacent LA potentials and with action potentials recorded from microelectrodes in adjacent LA cells). The sharp potential represented CS activation (timing coincided with action potentials recorded from CS musculature). A distal LA-CS connection (earliest sharp potential in the CS during lateral LA pacing) was located 26+/-7 mm from the ostium. During RA pacing posterior to the CS ostium, CS electrodes recorded septal-to-lateral activation of the high-frequency potential, with slightly later activation of the rounded potential (LA activation). Incisions surrounding the CS ostium isolating the ostium from the RA had no effect on the CS musculature and LA potentials during RA pacing within the isolated segment containing the CS ostium. RA pacing outside the isolated segment delayed activation of the CS musculature until after LA activation, confirming that the RA-CS connection was located in the region of the CS ostium as well as confirming the presence of the LA-CS connection. CONCLUSIONS: In canine hearts, the CS musculature is electrically connected to the RA and the LA and forms an RA-LA connection.


Subject(s)
Atrial Function , Heart Conduction System , Sinus of Valsalva/physiology , Animals , Cardiac Pacing, Artificial , Dogs , Electric Conductivity , Perfusion
19.
Circulation ; 98(5): 458-65, 1998 Aug 04.
Article in English | MEDLINE | ID: mdl-9714097

ABSTRACT

BACKGROUND: Clinical efficacy has driven the use of larger electrodes (7F, length > or =4 mm) for radiofrequency ablation, which reduces electrogram resolution and causes variability in tissue contact depending on electrode orientation. With active cooling, ablation electrode size may be reduced. The purpose of this study was to examine the effect of electrode length on tissue temperature and lesion size with saline irrigation used for active cooling. METHODS AND RESULTS: In 11 anesthetized dogs, the thigh muscle was exposed and bathed with heparinized canine blood. A 7F ablation catheter with a 2- or 5-mm irrigated tip electrode was positioned perpendicular or parallel to the thigh muscle. Radiofrequency current was delivered at constant voltage (50 V) for 30 seconds during saline irrigation (20 mL/min) to 148 sites. Tissue temperature at depths of 3.5 and 7 mm and lesion size were measured. In the perpendicular electrode-tissue orientation, radiofrequency applications at 50 V with the 2-mm electrode compared with the 5-mm electrode resulted in lower power at 50 V (26 versus 36 W) but higher tissue temperatures, larger lesion depth (8.0 versus 5.4 mm), and greater diameter (12.4 mm versus 8.4 mm). Also, in the parallel orientation, overall power was lower with the 2-mm electrode (25 versus 33 W), but tissue temperatures were higher and lesions were deeper (7.3 versus 6.9 mm). Lesion diameter was similar (11.1 versus 11.3 mm) for both electrodes. CONCLUSIONS: The smaller electrode resulted in transmission of a greater fraction of the radiofrequency power to the tissue and resulted in higher tissue temperature, larger lesions, and lower dependency of lesion size on the electrode orientation.


Subject(s)
Catheter Ablation/instrumentation , Animals , Catheter Ablation/methods , Catheter Ablation/statistics & numerical data , Chi-Square Distribution , Dogs , Electrodes/statistics & numerical data , Equipment Design , Evaluation Studies as Topic , Muscles/pathology , Muscles/surgery , Temperature , Thigh
20.
Pacing Clin Electrophysiol ; 21(6): 1279-86, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9633071

ABSTRACT

Recent studies have shown that typical atrial flutter (AFL) results from right atrial reentry around the tricuspid annulus (TA), constrained between the TA and crista terminalis (CT) on the free-wall and the TA and eustachian ridge (ER) on the septum. Creation of a complete line of conduction block across the subeustachian isthmus, between the TA and ER, eliminates AFL. The accuracy of fluoroscopy in localizing the anatomical boundaries and previous radiofrequency application sites is limited. This article describes an approach for utilizing a new three-dimensional nonfluoroscopic electroanatomical mapping system (CARTO) to examine the global right atrial activation pattern in patients during AFL, localize the anatomical boundaries, and create a complete line of conduction block by ablation across the subeustachian isthmus. During AFL, the locations of CT and ER are identified by double atrial potentials recorded along the intercaval region and between the inferior vena cava and coronary sinus ostium, respectively. Radiofrequency ablation across the subeustachian isthmus is performed during coronary sinus pacing. Beginning at TA, the ablation electrode is moved toward ER in 2-3 mm increments. Each movement is marked on the right atrial map to visualize the ablation line. In the event of residual conduction across the ablation line, defects in the ablation line are located by mapping along the previous ablation sites guided by CARTO system to locate the transition from the double atrial potentials (indicating block) to a single atrial potential (indicating conduction). Radiofrequency ablation to the site showing the single atrial potential along the ablation line produces complete conduction block across the subeustachian isthmus. In conclusion, the new electroanatomical mapping system allows precise 3-D localization of the anatomical boundaries of the AFL reentrant circuit, and facilitates ablation by accurately locating defects in the ablation line.


Subject(s)
Atrial Flutter/surgery , Catheter Ablation/methods , Image Processing, Computer-Assisted , Catheter Ablation/instrumentation , Electromagnetic Phenomena , Electrophysiology , Heart/anatomy & histology , Heart/physiology , Heart Block/etiology , Humans
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