bluuebunny/crossref_metadata_2025 huggingface dataset:
In situ hybridization and immunohistochemistry of versican, aggrecan and link protein, and histochemistry of hyaluronan in the developing mouse limb bud cartilage
Authors: Shibata S. , Fukada K. , Imai H. , Abe T. , Yamashita Y.
Published: October 2003

We investigated the expression pattern of versican, aggrecan, link protein and hyaluronan in the developing limb bud cartilage of the fetal mouse using in situ hybridization and/or immunohistochemistry. Versican mRNA and immunostaining were detected in the mesenchymal cell condensation of the future digital bone at E13. Versican mRNA expression rapidly disappeared from the tibial cartilage, as cartilage formation progressed during E13–15, but the immunostaining was gradually replaced by aggrecan immunostaining from the diaphysis. Immunostaining for both molecules thus had a ‘nega‐posi’ pattern and consequently versican immunostaining was still detected at the epiphyseal end at E15. This result indicated that versican functions as a temporary framework in newly formed cartilage matrix. An aggrecan‐positive region within the cartilage invariably had intense hyaluronan staining, whereas a versican‐positive region also had affinity for hyaluronan within the cartilage, but not in the mesenchymal cell condensation. Therefore, the presence of versican aggregates was not confirmed in the developing limb bud cartilage. Furthermore, although link protein was more closely related with aggrecan than versican during limb bud cartilage formation, there was a discrepancy between the expression of aggrecan and link protein in tibial cartilage at E15. In particular, only a link protein‐positive region was present in the marginal area of the metaphysis and the epiphysis at this stage. This finding may indicate a novel role for link protein.
How to measure the increase in elastic system fibres in the lamina propria of the uterine cervix of pregnant rats
Authors: Battlehner C. N. , Caldini E. G. , Pereira J. C. R. , Luque E. H. , Montes G. S.
Published: October 2003

As the uterus enlarges to accommodate the growing fetus during pregnancy, the cervix behaves essentially as a barrier. During ripening and delivery, it needs to become soft and distensible to allow dilation and the passage of the conceptus. As the transformations of the collagen‐containing fibres are known to be essential for ripening and delivery, it has been hypothesized that the elastic system fibres, owing to their intrinsic mechanical properties (reversible extensibility), could be involved in the shape‐recovering process immediately after delivery. In sections stained by Weigert's resorcin–fuchsin (with previous oxidation), we describe the elastic system fibres in the lamina propria of the rat uterine cervix. They are distributed following different patterns when in the endocervix or in the ectocervical–vaginal region. A third distinctive pattern (named the ‘elastic tendon’) is described here for the first time in the uterine–cervical transition. A special morphometrical protocol has been designed in order to overcome problems during the quantification process. Using the so‐called intercept counting method, it was possible to demonstrate that the elastic system fibres are increased in the cervix at the end of pregnancy. They may be involved in the immediate shape‐recovering of the cervix after delivery as well as in helping to strengthen the anchoring of the epithelium to the lamina propria, thus minimizing birth trauma.
Postnatal changes in caldesmon expression and localization in cardiac myocytes
Authors: McMartin Gail A. , Wirch Erwin , Abraham Natalia , Kargacin Gary J.
Published: October 2003

Caldesmon is a heat‐stable protein found in both muscle and non‐muscle tissue. It binds to a number of contractile and cytoskeletal proteins and may be involved in regulating acto‐myosin interaction in smooth muscle cells and/or the assembly of microfilaments in muscle and non‐muscle cells. We have shown previously that caldesmon is localized at the Z‐lines in adult cardiac myocytes and that both the low‐ and high‐molecular‐weight forms (l‐caldesmon and h‐caldesmon, respectively) are present in atrial and ventricular myocytes. Here we examined the expression of caldesmon and its localization in freshly isolated cardiac myocytes during postnatal development and when these myocytes were grown in culture. We found that l‐caldesmon is expressed in both neonatal and adult rat ventricular myocytes. The expression of h‐caldesmon, however, was not detected in myocytes from newborn animals but increased during the first 2 weeks of postnatal development. Caldesmon was generally not co‐localized with α‐actinin at the Z‐lines in neonatal myocytes but became increasingly more so during the first 2 weeks of postnatal development. When myocytes from 5‐ and 10‐day‐old rats were grown in primary culture, h‐caldesmon expression decreased and caldesmon could not be detected at the Z‐lines in the cultured cells. These results indicate that caldesmon plays a role at the Z‐lines in adult cardiac myocytes; however, its localization at the Z‐lines is not necessary for the prenatal development that occurs at these sites or for the establishment of a contractile phenotype in cultured cardiac myocytes.
The role of retinoic acid in the morphogenesis of the neural tube
Authors: Wilson L. , Gale E. , Maden M.
Published: October 2003

We have examined the role of the signalling molecule, retinoic acid, in the process of neurulation and the subsequent growth and differentiation of the central nervous system using quail embryos that have developed in the absence of retinoic acid. Such retinoic acid‐free embryos undergo abnormal neural tube formation in terms of its shape and structure, but the embryos do not display spina bifida or exencephaly. The neural tubes have a wider floor plate, a thicker roof plate and a different dorsoventral shape. Phalloidin staining and electron microscopy revealed alterations in the actin filaments and the junctional complexes of the cell layer lining the lumen. Initially the neural tubes proliferated at the same rate as normal, but later the proliferation rate declined drastically and neuronal differentiation was highly deficient. There were very few motoneurons extending neurites into the periphery, and within the neural tube axon trajectories were chaotic. These results reveal several functions for retinoic acid in the morphogenesis and growth of the neural tube, many of which can be explained by defective notochord signalling, but they do not suggest that this molecule plays a role in neural tube closure.
Morphological analysis of leucocyte transmigration in the pleural cavity
Authors: Teng R. , Johkura K. , Ogiwara N. , Zhao X. , Cui L. , Iida I. , Okouchi Y. , Asanuma K. , Sasaki K.
Published: October 2003

The role that pleural mesothelial cells play in leucocyte transmigration into the pleural cavity was investigated in lipopolysaccharide‐stimulated mice. Changes in mesothelial cell morphology and changes in expression of adhesion molecules on mesothelial cells and leucocytes were analysed by light microscopy, immunohistochemistry, transmission electron microscopy (TEM) and immuno‐scanning electron microscopy (immuno‐SEM). After stimulation, the mesothelial cells separated completely from one another before leucocyte penetration across the mesothelial layer occurred. These changes occurred primarily in the immediate vicinity of ribs, where a large number of leucocytes accumulated. Immuno‐SEM showed that the expression of intercellular adhesion molecule‐1 (ICAM‐1) on the parietal pleural mesothelial cells was significantly up‐regulated by lipopolysaccharide stimulation, and that of vascular cell adhesion molecule‐1 (VCAM‐1) was induced. Both were restricted to the microvilli of the mesothelial cells. By contrast, expression of intercellular adhesion molecule‐2 (ICAM‐2), platelet/endothelial cell adhesion molecule‐1 (PECAM‐1), mucosal addressin cell adhesion molecule‐1 (MAdCAM‐1), endothelial leucocyte adhesion molecule‐1 (ELAM‐1), peripheral node addressin (PNAd) and fibronectin were not detected. Lymphocyte function associated antigen‐1 (LFA‐1), macrophage‐1 molecule (Mac‐1) and very late appearing antigen‐4 (VLA‐4), all ligands of ICAM‐1 and VCAM‐1, were present on the transmigrated neutrophils and macrophages. These findings demonstrate that the immediate vicinity of ribs is a source of leucocyte migration into the pleural space.
Recent Developments in the Quest for Myoclonic Epilepsy Genes
Authors: Delgado‐Escueta Antonio V. , Perez‐Gosiengfiao Katerina B. , Bai Dongsheng , Bailey Julia , Medina Marco T. , Morita Ryoji , Suzuki Toshimitsu , Ganesh Subramaniam , Sugimoto Toshihisa , Yamakawa Kazuhiro , Ochoa Adriana , Jara‐Prado A. , Rasmussen Astrid , Ramos‐Peek J. , Cordova Sergio , Rubio‐Donnadieu Francisco , Alonso Maria Elisa
Published: October 2003

Summary:  Understanding the latest advances in the molecular genetics of the epilepsies is important, as it provides a basis for comprehending the new practice of epileptology. Epilepsies have traditionally been classified and subtyped on the basis of clinical and neurophysiologic concepts. However, the complexity and variability of phenotypes and overlapping clinical features limit the resolution of phenotype‐based classification and confound epilepsy nosology. Identification of tightly linked epilepsy DNA markers and discovery of epilepsy‐causing mutations provide a basis for refining the classification of epilepsies. Recent discoveries regarding the genetics surrounding certain epilepsy types (including Lafora's progressive myoclonic epilepsy, the severe myoclonic epilepsy of infancy of Dravet, and idiopathic generalized epilepsies) may be the beginning of a better understanding of how rare Mendelian epilepsy genes and their genetic architecture can explain some complexities of the common epilepsies.
Clinical Presentations and Phenomenology of Myoclonus
Authors: Faught Edward
Published: October 2003

Summary:  The term “myoclonus” has been used to describe heterogeneous phenomena involving sudden movements, but there is no generally accepted, precise definition of myoclonus. Myoclonus can often be classified based on electroencephalographic (EEG) and/or electromyographic (EMG) data. Some myoclonic epilepsy syndromes, including juvenile myoclonic epilepsy, may frequently be misdiagnosed because of failure to obtain a complete patient history and/or failure to appreciate characteristic EEG changes. A good understanding of the features associated with myoclonic disorders (particularly the myoclonic epilepsies) and of features associated with other neurologic disorders that are often confused with myoclonic disorders is an invaluable aid in obtaining an accurate diagnosis and will ultimately help in determining the best course of treatment for patients.
Classification of the Myoclonic Epilepsies
Authors: Leppik Ilo E.
Published: October 2003

Summary:  The myoclonic epilepsies are a collection of syndromes in which myoclonic seizures are a prominent feature. Proper classification of a patient's syndrome is critical for appropriate treatment and prognosis. However, classification of such syndromes is often difficult because the terminology used to describe seizures can be confusing and inconsistent. Myoclonic epilepsy syndromes can be epileptic or nonepileptic and can also be divided into inherited and acquired forms. Progressive myoclonic epilepsy (PME) syndromes are the most severe of the myoclonic epilepsies. Diagnosis of PME syndromes on clinical grounds can be difficult, but advances in genetic testing have made diagnoses more accurate. Some other benign myoclonic epilepsy syndromes also have identified gene markers, which can aid in diagnosis. To accurately classify a patient's epilepsy syndrome, clinicians should use all available clinical laboratory tools appropriately. Improved accuracy of diagnosis for patients with myoclonic epilepsies should lead to more dependable prognoses and more effective treatment.
Treatment Strategies for Myoclonic Seizures and Epilepsy Syndromes with Myoclonic Seizures
Authors: Wheless James W. , Sankar Raman
Published: October 2003

Summary: Despite the availability of numerous treatment options, the diagnosis and treatment of myoclonic seizures continue to be challenging. Based on clinical experience, valproate and benzodiazepines have historically been used to treat myoclonic seizures. However, many more treatment options exist today, and the clinician must match the appropriate treatment with the patient's epilepsy syndrome and its underlying etiology. Comorbidities and other medications must also be considered when making decisions regarding treatment. Rarely, some antiepileptic drugs may exacerbate myoclonic seizures. Most epileptic myoclonus can be treated pharmacologically, but some cases respond better to surgery, the ketogenic diet, or vagus nerve stimulation. Because myoclonic seizures can be difficult to treat, clinicians should be flexible in their approach and tailor therapy to each patient.
ICD Nocardiosis
Authors: O'ROURKE SEAN , KAPOOR SHALINI , CARTER‐ADKINS DANIELLE , PACHULSKI ROMAN T.
Published: October 2003

We present an initial report of Nocardia asteroides implantable cardioverter defibrillator infection. Systemic infection persisted despite pulse generator explant and several years of appropriate antibiotic therapy. Without epicardial lead system removal, chronic pleuropericardial disease developed. (J Interven Cardiol 2003;16:375–376)
The Role of Enoxaparin in Interventional Management of Patients with Acute Coronary Syndromes
Authors: GRINES CINDY L. , O'NEILL WILLIAM
Published: October 2003

Interventional management strategies involving early angiography and percutaneous coronary intervention (PCI) are increasingly widespread in the management of patients with acute coronary syndromes (ACS). Notwithstanding the benefits of early intervention, there is a significant risk of postprocedural thrombotic complications and a need to optimize antithrombotic regimens for use before and during PCI. It is clear that the current standard therapy with unfractionated heparin (UFH) and aspirin can be improved upon, in terms of both efficacy and safety. The low‐molecular‐weight heparin(s) (LMWHs) offer pharmacologic and practical advantages over UFH. The LMWH enoxaparin has recently emerged as the anticoagulant of choice for the acute management of ACS. Enoxaparin has also demonstrated sustained benefits over UFH in patients proceeding to PCI, and as a procedural anticoagulant. Combination therapy with enoxaparin and a glycoprotein IIb/IIIa inhibitor may further improve the efficacy and safety of antithrombotic treatment during coronary interventions, as a result of the drugs' complementary mechanisms of action. Early clinical evidence supports the use of enoxaparin in combination with glycoprotein IIb/IIIa inhibitors in high‐risk patients with ACS. Ongoing, large‐scale, randomized controlled studies will help to clarify the role of enoxaparin in interventional cardiology, either as the primary anticoagulant or as part of a combination regimen, and to define optimal regimens for treatment. (J Interven Cardiol 2003;16:357–366)
Transluminal Angioplasty in a Patient with a Single Coronary Artery During the Acute Phase of a Myocardial Infarction
Authors: BOULET VINCENT , LIPIECKI JANUSZ , PHILIPPOT FRANÇOIS , DUREL NICOLAS , TAURIAC OLIVIER de , AMONCHOT AIMÉ , CITRON BERNARD , PONSONNAILLE JEAN
Published: October 2003

The prevalence of coronary artery abnormalities, in particular the single vessel form, is low among the general population. We report a case of a transluminal angioplasty of the left anterior descending artery arising from the right coronary artery during the acute phase of myocardial infarction. (J Interven Cardiol 2003;16:371–374)
Radiofrequency Catheter Ablation of Fast Pathway via Unconventional Right Subclavian Venous Access for Atrioventricular Nodal Reentrant Tachycardia
Authors: MACHADO CHRISTIAN , LIDDON VICKI , ROY DEBAJIT
Published: October 2003

We report the case of a patient with atrioventricular nodal reentry tachycardia (AVNRT), who was found to have obstruction of the inferior vena cava (IVC) by a calcified mass during an electrophysiologic study (EPS). Subsequently, complete EPS was performed via a combined right internal jugular and subclavian venous access. Successful radiofrequency catheter ablation of the fast pathway was performed via the unconventional right subclavian venous route. (J Interven Cardiol 2003;16:377–380)
Advances in Transcatheter Patch Occlusion of Heart Defects
Authors: SIDERIS E. B.
Published: October 2003

The transcatheter patch device consists of the following components: a sleeve type polyurethane patch, a double balloon support catheter and a retrieval thread. It has been applied in a variety of heart defects, including various types of atrial septal defects, ventricular septal defects and patent ductus arteriosus. New advances include an accelerated release time for many applications and better immobilization. Using accelerated fibrin formation principles, transcatheter path release time has been decreased to less than 24 hours for patent ductus arteriosus and some ventricular septal defects; in contrast 48 hours are required for patch release in large atrial septal defects. The device is also unlikely to move away from the septum using the new immobilization methods. Since the patch is inflatable, only three sizes are required for the occlusion of all defect types and sizes. Conclusion: In conclusion the transcatheter patch is applicable in a variety of heart defects; the procedure is safer and faster, becoming outpatient, for many applications. Furthermore, it is cost effective. (J Interven Cardiol 2003;16:419–424)
Stent Implantation for Coarctation in Adults
Authors: PIÉCHAUD JEAN‐FRANÇOIS
Published: October 2003

Transcatheter dilatation is considered the elective treatment of residual coarctation. In the presence of native coarctation, dilatation is often effective but in the first months of life, and the risk of aneurysm formation is not low. The use of stents in adolescents and adults provides excellent results and seems to reduce the complication and aneurysm rates. A perfect technique, now well codified, is necessary. (J Interven Cardiol 2003;16:413–418)
Device Closure of Patent Ductus Arteriosus
Authors: ARORA RAMESH , SENGUPTA PARTHO P. , THAKUR ASHISH K. , MEHTA VIMAL , TREHAN VIJAY
Published: October 2003

(J Interven Cardiol 2003;16:385–391)
ASD Closure with the Amplatzer Device
Authors: FAELLA HORACIO J. , SCIEGATA ALBERTO M. , ALONSO JOSÉ L. , JMELNITSKY LUIS
Published: October 2003

We report the safety and efficacy of the Amplatzer device for transcatheter closure of ASD and fenestrated Fontan in children and adults. One hundred and two patients underwent transcatheter occlusion of the defect. The median age of the patients was 18.2 years, the median size of the ASDs by TEE was 17.6 mm, the median balloon‐stretched diameter was 19.9 mm, and the median size of the device implanted was 20 mm. Immediately after the release of the device, color Doppler echocardiography revealed no residual shunt in 92 (90.19%) of 102 patients. At 24 hours all the patients 101/101 (100%) had complete closure. The minor complications encountered after the procedure were atrial arrhythmias in 4 patients. The only major complication we had was a baby who died. In conclusion, the ASO device is a safe and effective device for catheter closure of most secundum ASDs and fenestrated Fontan. (J Interven Cardiol 2003;16:393–397)
Catheter Closure of Congenital/Acquired Muscular VSDs and Perimembranous VSDs Using the Amplatzer Devices
Authors: D. THANOPOULOS BASIL (VASILIOS) , KARANASSIOS EVANGELOS , TSAOUSIS GEORGE , PAPADOPOULOS GEORGE S. , STEFANADIS CHRISTODOULOS
Published: October 2003

Over the past 10 years a variety of occluding devices has been used for transcatheter closure of ventricular septal defects (VSDs), but none has gained wide acceptance. This article presents the experience of transcatheter closure of muscular and perimembranous VSDs in 22 and 13 patients, respectively, with the new Amplatzer VSD occluders. Overall total occlusion was achieved in 95% and 92.3% of patients with muscular and perimembranous VSDs, respectively. The main complication was embolization of the device in 1/13 (7.6%) patients with perimembranous VSDs. Transcatheter closure of VSDs using the Amplatzer VSD occluders appears to be a safe and effective alternative to the standard surgical treatment. (J Interven Cardiol 2003;16:399–407)
Catheter Closure of Secundum ASD Using “Other” Devices
Authors: SCHRÄDER RAINER
Published: October 2003

The first nonoperative ASD closure was performed by Noel L. Mills and Terry D. King in a 17‐year old female patient on April 8, 1975. In the following years there was little interest in this clinical field after trials with the “Clamshell Device” had been discontinued because of arm fractures. From the late 1980s until the mid 1990s E. B. Sideris (“Buttoned Device”) and U.U. Babic (“ASDOS”) kept the ideas of King&Mills alive while G.S. Das developed the first self‐centering device (“AngelWings”). Clinical trials with ASDOS and AngelWings have been stopped because of complicated technology and risk of perforation. The Buttoned Device and its modifications are still used with high success rates even in defects >20 mm and low long‐term risk of perforation. Since the pioneering works of King & Mills marked improvements in devices and delivery systems have been achieved. After almost three decades of ongoing research and development, transcatheter ASD closure has become a clinical routine procedure. (J Interven Cardiol 2003;16:409–412)
Techniques and Applications of Transcatheter Embolization Procedures in Pediatric Cardiology
Authors: SIM JAMES Y. , ALEJOS JUAN C. , MOORE JOHN W.
Published: October 2003

Transcatheter embolization of congenital or acquired superfluous vascular structure has become routine procedures performed by interventional pediatric cardiologists. Embolization procedure is often part of a collaborative effort with cardiac surgeons to palliate complex congenital heart defect, such as in embolizing aortopulmonary collateral arteries in patient with single ventricle physiology. In other cases, the procedure is the definitive treatment as in embolizing coronary artery fistula. Pediatric cardiologists performing embolization procedures should be familiar with available technologies as well as understand the underlying cardiac anatomy and pathophysiology. This article provides a comprehensive review of presently available embolization agents and technologies. Some of the technologies are used only by interventional radiologists but may be useful to pediatric cardiologists. Specific clinical applications in pediatric cardiology are also discussed with summary of current literature. With continue advancement in transcatheter technology and operator expertise, all unwanted vascular communication should be amenable to transcatheter embolization. (J Interven Cardiol 2003;16:425–448)
Pulmonary Venous Wedge Pressure Provides an Accurate Assessment of Pulmonary Artery Pressure in Children with a Bidirectional Glenn Shunt
Authors: GRUENSTEIN DANIEL H. , SPICER ROBERT L. , SHIM DAVID , BEEKMAN ROBERT H.
Published: October 2003

Purpose: In circulations with pulsatile pulmonary artery flow the pulmonary venous wedge pressure (PVWp) has been validated as a good estimate of pulmonary artery pressure (PAp), when PAp is low. The purpose of this study was to validate PVWp estimates of PAp in the less‐pulsatile pulmonary circulation of children after bidirectional Glenn shunts. Methods: A retrospective study was performed of 22 simultaneous measurements of PVWp and PAp made during 20 catheterizations in 19 children who had undergone bidirectional Glenn procedures. The PAp was measured directly from the branch PA ipsilateral to the side of the PVWp, or in the SVC. Pulmonary resistance (Rp) was calculated with both PAp and PVWp, to assess the impact of PAp estimates on Rp determinations. Results: Patients ranged in age from 5 months to 10.7 years. There were a variety of univentricular cardiac malformations in the study group. Two children had antegrade pulmonary blood flow in addition to a bidirectional Glenn shunt. The mean PAp ranged from 4 to 14 mmHg, while mean PVWp ranged from 3 to 15 mmHg. Mean PVWp never differed from mean PAp by more than 3 mmHg. There was a significant linear relation between mean PAp and PVWp: PAp = 0.86 (PVWp) + 2.0 (R2= 0.89; P < 0.0001). PVWp provided a good approximation of PAp regardless of the presence (n = 2) or absence (n = 19) of antegrade pulmonary flow. There was a good linear correlation between the Rp calculated by both methods (RpPAp = 0.9 (RpVWp) + 0.5; R2= 0.74; P < 0.0001). Conclusion: The mean PVWp provides a close approximation of mean PAp in children with a bidirectional Glenn shunt and provides valuable hemodynamic information in cases where direct PAp measurements are unavailable. (J Interven Cardiol 2003;16:367–370)
Left Ventricular Wall Hematoma and Cardiac Tamponade Complicating Percutaneous Coronary Intervention Using IIb/IIIa Receptor Antagonists
Authors: MIEGHEM CARLOS VAN , DENS JO , HERREGODS MARIE‐CHRISTINE , DESMET WALTER
Published: October 2003

A case of intramyocardial hematoma and cardiac tamponade after complicated percutaneous coronary intervention is reported. Hemorrhage as a result of the antiplatelet effect of IIb/IIIa receptor antagonists is the considered underlying mechanism. (J Interven Cardiol 2003;16:381–384)
Successful Direct Stenting Guided by Intravascular Ultrasound without Contrast in a Patient with Renal Dysfunction
Authors: REZKALLA SHEREIF H.
Published: October 2003

We report a 60‐year‐old male with significant renal dysfunction who had a recent coronary angiography with mid coronary stenosis. To avoid worsening of his kidney failure, we performed primary stenting with a combination of intravascular ultrasound and a marker wire. No dye was used during the stenting procedure. Whereas this new technique needs to be validated in studies, it represents new hope for such patients. (J Interven Cardiol 2003;16:449–453)
One‐Dimensional Rabbit Sinoatrial Node Models:
Authors: GARNY ALAN , KOHL PETER , HUNTER PETER J. , BOYETT MARK R. , NOBLE DENIS
Published: October 2003

Introduction: Cardiac multicellular modeling has traditionally focused on ventricular electromechanics. More recently, models of the atria have started to emerge, and there is much interest in addressing sinoatrial node structure and function.

Methods and Results: We implemented a variety of one‐dimensional sinoatrial models consisting of descriptions of central, transitional, and peripheral sinoatrial node cells, as well as rabbit or human atrial cells. These one‐dimensional models were implemented using CMISS on an SGI® Origin® 2000 supercomputer. Intercellular coupling parameters recorded in experimental studies on sinoatrial node and atrial cell‐pairs under‐represent the electrotonic interactions that any cardiomyocyte would have in a multidimensional setting. Unsurprisingly, cell‐to‐cell coupling had to be scaled‐up (by a factor of 5) in order to obtain a stable leading pacemaker site in the sinoatrial node center. Further critical parameters include the gradual increase in intercellular coupling from sinoatrial node center to periphery, and the presence of electrotonic interaction with atrial cells. Interestingly, the electrotonic effect of the atrium on sinoatrial node periphery is best described as opposing depolarization, rather than necessarily hyperpolarizing, as often assumed.

Conclusion: Multicellular one‐dimensional models of sinoatrial node and atrium can provide useful insight into the origin and spread of normal cardiac excitation. They require larger than “physiologic” intercellular conductivities in order to make up for a lack of “anatomical” spatial scaling. Multicellular models for more in‐depth quantitative studies will require more realistic anatomico‐physiologic properties. (J Cardiovasc Electrophysiol, Vol. 14, pp. S121‐S132, October 2003, Suppl.)
Mechanisms of Termination of Atrial Fibrillation by Class I Antiarrhythmic Drugs:
Authors: NATTEL STANLEY , KNELLER JAMES , ZOU RENQIANG , LEON L. JOSHUA
Published: October 2003

Sodium channel blocking drugs (Class I antiarrhythmic agents) have been used for the termination of atrial fibrillation (AF) and for sinus rhythm maintenance for almost 100 years. Despite this long history, the mechanisms that underlie their efficacy in AF remain poorly understood. Classic notions about the determinants of cardiac reentry, as embodied in leading circle theory, and of AF, as reflected in the multiple wavelet hypothesis, suggest that cardiac conduction slowing should promote, rather than prevent, AF. This article reviews the evidence (both clinical and experimental) for the efficacy and mechanisms of action of Class I antiarrhythmic agents in AF. Application of mathematical models of AF to the evaluation of Class I mechanisms is discussed, and recent insights into the latter are presented. A better understanding of the ways in which Na+ channel blockers affect AF will be useful, not only for new antiarrhythmic drug development but also for gaining insight into the mechanisms of the arrhythmia. (J Cardiovasc Electrophysiol, Vol. 14, pp. S133‐S139, October 2003, Suppl.)
The Electrical Restitution Curve Revisited:
Authors: FRANZ MICHAEL R.
Published: October 2003

The electrical restitution curve (ERC) traditionally describes the recovery of action potential duration (APD) as a function of the interbeat interval or, more correctly, the diastolic interval (DI). Often overlooked in modeling studies, the normal ventricular ERC is triphasic, starting with a steep initial recovery at the shortest DIs, a transient decline, and a final asymptotic rise to a plateau phase reached at long DIs. Recent studies have proposed that it would be advantageous to lower the slope of the ERC by drug intervention, as this might reduce the potential for electrical alternans and ventricular fibrillation. This review discusses the pros and cons of a flat versus steep slope of the ERC and draws attention to mechanisms that justify the (physiologically) steep slope, rather than a flat slope, as a better design against arrhythmias. Five potential mechanisms are discussed, which allows for a different interpretation of the effect of the slope on arrhythmogenicity. The most important appears to be the physiologic rate adaptive shortening of APD that, by reciprocal lengthening of the DI, allows the subsequent APD to move more quickly from the steep initial ERC phase onto the flat phase. A less steep initial ERC phase would protract the transition toward more fully recovered APD and, in fact, may perpetuate electrical alternans. The triphasic ERC time course in normal myocardium cannot be explained by or fitted to single exponentials or single ion channel recovery kinetics. A simple tri‐ionic model is suggested that may help explain the shape of the ERC at various repolarization levels and place APD recovery into perspective with intracellular calcium recycling and recovery of contractile force. (J Cardiovasc Electrophysiol, Vol. 14, pp. S140‐S147, October 2003, Suppl.)
Left Atrial Conduction Along the Coronary Sinus During Ectopic Atrial Tachycardia and Atrial Fibrillation:
Authors: CARLSON JONAS , SANTOS SUSANA , PLATONOV PYOTR G. , RASMUSSEN OLE KONGSTAD , JOHANSSON ROLF , OLSSON S. BERTIL
Published: October 2003

Introduction: Correlation function analysis was applied to endocardial electrograms to investigate conduction patterns along the coronary sinus (CS) during sinus rhythm (SR) and atrial tachycardias.

Methods and Results: Eighteen recordings were obtained from 14 patients with supraventricular tachycardias. Five atrial fibrillation (AF) recordings were compared to 10 SR recordings and 3 ectopic atrial tachycardia (EAT) recordings. The maximum correlation coefficient was used to assess similarity between signals, i.e., if they originate from the same wavefront. The cumulative time delay, calculated as pairwise summation of interelectrode time delays, was used as an indicator of activation sequence along the CS. Method validation using SR showed right‐to‐left conduction with high correlations in 8 of 10 recordings indicating one single wavefront. EAT recordings showed consistent left‐to‐right conduction with left atrial foci and right‐to‐left with right atrial focus and lower correlations than SR. All 5 AF recordings showed predominantly left‐to‐right conduction direction, also with correlations lower than SR.

Conclusion: (1) Correlation function analysis can be used to assess agreement between signals and direction of activation spread. (2) Due to the position of CS, the results can be used to derive mechanisms of interatrial conduction. (3) Consistency in electrical activity propagation along CS is common in AF. (J Cardiovasc Electrophysiol, Vol. 14, pp. S148‐S153, October 2003, Suppl.)
Frequency Measures Obtained from the Surface Electrocardiogram in Atrial Fibrillation Research and Clinical Decision‐Making
Authors: BOLLMANN ANDREAS , HUSSER DANIELA , STRIDH MARTIN , SOERNMO LEIF , MAJIC MONICA , KLEIN HELMUT U. , OLSSON S. BERTIL
Published: October 2003

Introduction: Frequency analysis of fibrillation (FAF) and time‐frequency analysis (TFA) were developed recently in order to quantify atrial electrical remodeling in atrial fibrillation (AF) from the surface ECG. This article describes the experience with these two different frequency analysis techniques in consecutive AF patients and discusses possible applications in AF research and clinical decision‐making.

Methods and Results: Baseline 2‐minute, high‐gain, high‐resolution ECG recordings using three bipolar leads were obtained from 80 consecutive patients with AF lasting >24 hours. A power spectrum was obtained using Fourier analysis following spatiotemporal QRST cancellation. The dominant fibrillatory rate (in fibrillations per minute [fpm]) was derived (FAF). Stability of the instantaneous fibrillatory rate measured in overlapping 1‐second segments was expressed as the segment proportion with consecutive rate differences <6 fpm (TFA). An adequate power spectrum that could be submitted for determination of fibrillatory rate was obtained in all patients. Dominant atrial rates ranged between 288 and 534 fpm and showed a high correlation (R = 0. 878–0.911, P < 0.001) when assessed from the three different leads. The average instantaneous fibrillatory rate was inversely related with its stability (R =−0.417, P < 0.001). It was closely related with the dominant fibrillatory rate obtained from FAF (R = 0.948, P < 0.001). A literature review revealed that pharmacologic or electrical cardioversion and AF pace termination success rates were highly dependent on fibrillatory rate.

Conclusion: Atrial fibrillatory rate and its variability can be reliable obtained from the surface ECG in AF patients. These parameters exhibit a significant interindividual variability allowing individual quantification of the atrial electrical remodeling process and might prove useful for predicting therapy efficacy. (J Cardiovasc Electrophysiol, Vol. 14, pp. S154‐S161, October 2003, Suppl.)
Echocardiographic and Electrocardiographic Predictors for Atrial Fibrillation Recurrence Following Cardioversion
Authors: BOLLMANN ANDREAS , HUSSER DANIELA , STEINERT REIKO , STRIDH MARTIN , SOERNMO LEIF , OLSSON S. BERTIL , POLYWKA DANIELA , MOLLING JOCHEN , GELLER CHRISTOPH , KLEIN HELMUT U.
Published: October 2003

Introduction: Identification of suitable candidates for cardioversion currently is not based on individual electrical and mechanical atrial remodeling. Therefore, this study analyzed the meaning of atrial fibrillatory rate obtained from the surface ECG (as a measure of electrical remodeling) and left atrial size (as measure of mechanical remodeling) for prediction of early atrial fibrillation (AF) recurrence following cardioversion.

Methods and Results: Forty‐four consecutive patients (26 men and 18 women, mean age 62 ± 11 years, no antiarrhythmic medication at baseline) with persistent AF were studied. Fibrillatory rate was obtained from high‐gain, high‐resolution surface ECG using digital signal processing (filtering, QRST subtraction, Fourier analysis) before electrical cardioversion. Univariate and multivariate regression analysis revealed larger systolic left atrial area (Beta = 0.176, P = 0.031) obtained by precardioversion echocardiogram from the apical four‐chamber view and higher atrial fibrillatory rate (Beta = 0.029, P = 0.021) to be independent predictors for AF recurrence (n = 13). Stratification based on the regression equation (electromechanical index [EMI]= 0.176 systolic left atrial area + 0.029 fibrillatory rate − 17.674) allowed identification of groups at low, intermediate, or high risk. No patient with an EMI < −1.85 had early AF recurrence, as opposed to 78% with an EMI > −0.25. Intermediate results (40% recurrence rate) were obtained when the calculated EMI ranged between −1.85 and −0.25 (P < 0.001).

Conclusion: Fibrillatory rate obtained from the surface ECG and systolic left atrial area obtained by echocardiography may predict early AF recurrence in patients with persistent AF. These parameters might be useful in identifying candidates with a high likelihood of remaining in sinus rhythm after cardioversion. (J Cardiovasc Electrophysiol, Vol. 14, pp. S162‐S165, October 2003, Suppl.)
Atrial Excitation Assuming Uniform Propagation
Authors: DAM PETER M. van , OOSTEROM ADRIAAN van
Published: October 2003

Introduction: We investigated the spread of the excitation wave over the atria following initiation in a given focus in an atrial model containing its overall geometry only, i.e., without atrial bundles.

Methods and Results: The propagation velocity of the excitation wave was taken to be uniform, and the wall thickness was discarded. The timing of excitation of any point on the atrium thus becomes directly proportional to its shortest distance over the atrial wall to the focus. Despite these gross simplifications, the general nature of the excitation sequence found corresponded closely to clinical data reported in the literature. This suggests that the complex overall geometry of the atria dominates the timing of the excitation. A highly intriguing observation from this study was that, when looking at the pathways from the sinus node to all other points on the atrium, prominent routes became visible even though no such pathways formed part of the model of the atrial geometry used. The locations of these prominent routes coincide with those of various distinct bundles in the atria. Possible inferences of these observations are discussed.

Conclusion: Based upon comparison with data from other studies, it is concluded that, during stable heart rhythms, propagation of the atrial excitation wave is well approximated by an assumption of uniform velocity, even though no atrial bundles were included in the model. The overall geometry seems to be the dominant factor in the spread of excitation. (J Cardiovasc Electrophysiol, Vol. 14, pp. S166‐S171, October 2003, Suppl.)
Study of Unipolar Electrogram Morphology in a Computer Model of Atrial Fibrillation
Authors: JACQUEMET VINCENT , VIRAG NATHALIE , IHARA ZENICHI , DANG LAM , BLANC OLIVIER , ZOZOR STEEVE , VESIN JEAN‐MARC , KAPPENBERGER LUKAS , HENRIQUEZ CRAIG
Published: October 2003

Introduction: Electrograms exhibit a wide variety of morphologies during atrial fibrillation (AF). The basis of these time courses, however, is not completely understood. In this study, data from computer models were studied to relate features of the signals to the underlying dynamics and tissue substrate.

Methods and Results: A computer model of entire human atria with a gross fiber architecture based on histology and membrane kinetics based on the Courtemanche et al. atrial model was developed to simulate paced activation and simulated AF. Unipolar electrograms were computed using a current source approximation at 256 sites in right atrium, to simulate a mapping array. The results show the following: (1) In a homogeneous and isotropic tissue, the presence of highly asymmetric electrograms is rare (<2%), although there is a marked variability in amplitude and symmetry. (2) The introduction of anisotropy increases this variability in symmetry and amplitude of the, electrograms especially for propagation across fibers. The percentage of highly asymmetric electrograms increases to 12% to 15% for anisotropy ratios greater than 3:1. (3) Multiphasic and fractionated electrograms are rarely seen in the model with uniform properties but are more common (15%–17%) in a model including regions with abrupt changes in conductivity. Beat‐to‐beat variations in the occurrence of multiphasic signals are possible with fixed anatomic heterogeneity, due to beat‐to‐beat variations in the direction of the wavefront relative to the heterogeneity.

Conclusion: Analysis of the amplitude and symmetry of unipolar atrial electrograms can provide information about the electrophysiologic substrate maintaining AF. (J Cardiovasc Electrophysiol, Vol. 14, pp. S172‐S179, October 2003, Suppl.)
The Dominant T Wave and Its Significance
Authors: OOSTEROM ADRIAAN van
Published: October 2003

Introduction: The shapes of the T waves as observed in different leads placed on the thorax are very similar. The dominant T wave is introduced as a means to characterize this general signal shape. Its relationship to the transmembrane potentials of cardiac myocytes is discussed.

Methods and Results: The source description of a biophysical model that previously was shown to yield realistic T waveforms was analyzed in order to exploit its relation to the transmembrane potentials of the cardiac myocytes at the surface bounding the myocardium. The product of this analysis is the dominant T wave: a waveform that describes the slope of the transmembrane potential. It is shown that the dominant T wave can be estimated easily from the matrix of sampled lead potentials. The timing of its peak reveals the mean of the repolarization times of the involved transmembrane potentials. The amplitude of the peak is the maximum downward slope of the transmembrane potential. This amplitude is independent of the volume conductor effects of the tissues surrounding the heart. The estimate of the dominant T wave retains this property.

Conclusion: The dominant T wave reflects the derivative of the recovery phase of a generalized transmembrane potential. Its amplitude is independent of the volume conductor properties of the tissues surrounding the heart. This is a unique feature that greatly facilitates the interpretation and application of the other signal features of the dominant T wave. (J Cardiovasc Electrophysiol, Vol. 14, pp. S180‐S187, October 2003, Suppl.)
Timing of Depolarization and Contraction in the Paced Canine Left Ventricle:
Authors: KERCKHOFFS ROY C.P. , FARIS OWEN P. , BOVENDEERD PETER H.M. , PRINZEN FRITS W. , SMITS KAREL , McVEIGH ELLIOT R. , ARTS THEO
Published: October 2003

Introduction: For efficient pump function, contraction of the heart should be as synchronous as possible. Ventricular pacing induces asynchrony of depolarization and contraction. The degree of asynchrony depends on the position of the pacing electrode. The aim of this study was to extend an existing numerical model of electromechanics in the left ventricle (LV) to the application of ventricular pacing. With the model, the relation between pacing site and patterns of depolarization and contraction was investigated.

Methods and Results: The LV was approximated by a thick‐walled ellipsoid with a realistic myofiber orientation. Propagation of the depolarization wave was described by the eikonal‐diffusion equation, in which five parameters play a role: myocardial and subendocardial velocity of wave propagation along the myofiber cm and ce; myocardial and subendocardial anisotropy am and ae; and parameter k, describing the influence of wave curvature on wave velocity. Parameters cm, ae, and k were taken from literature. Parameters am and ce were estimated by fitting the model to experimental data, obtained by pacing the canine left ventricular free wall (LVFW). The best fit was found with cm= 0.75 m/s, ce= 1.3 m/s, am= 2.5, ae= 1.5, and k= 2.1 × 10−4 m2/s. With these parameter settings, for right ventricular apex (RVA) pacing, the depolarization times were realistically simulated as also shown by the wavefronts and the time needed to activate the LVFW. The moment of depolarization was used to initiate myofiber contraction in a model of LV mechanics. For both pacing situations, mid‐wall circumferential strains and onset of myofiber shortening were obtained.

Conclusion: With a relatively simple model setup, simulated depolarization timing patterns agreed with measurements for pacing at the LVFW and RVA in an LV. Myocardial cross‐fiber wave velocity is estimated to be 0.40 times the velocity along the myofiber direction (0.75 m/s). Subendocardial wave velocity is about 1.7 times faster than in the rest of the myocardium, but about 3 times slower than as found in Purkinje fibers. Furthermore, model and experiment agreed in the following respects. (1) Ventricular pacing decreased both systolic pressure and ejection fraction relative to natural sinus rhythm. (2) In early depolarized regions, early shortening was observed in the isovolumic contraction phase; in late depolarized regions, myofibers were stretched in this phase. Maps showing timing of onset of shortening were similar to previously measured maps in which wave velocity of contraction appeared similar to that of depolarization. (J Cardiovasc Electrophysiol, Vol. 14, pp. S188‐S195, October 2003, Suppl.)
Relationship Between Regional Shortening and Asynchronous Electrical Activation in a Three‐Dimensional Model of Ventricular Electromechanics
Authors: USYK TARAS P. , McCULLOCH ANDREW D.
Published: October 2003

Introduction: Asynchronous electrical activation can cause abnormalities in perfusion and pump function. An electromechanical model was used to investigate the mechanical effects of altered cardiac activation sequence.

Methods and Results: We used an anatomically detailed three‐dimensional computational model of the canine ventricular walls to investigate the relationship between regional electrical activation and the timing of fiber shortening during normal and ventricular paced beats. By including a simplified Purkinje fiber network and anisotropic impulse conduction in the model, computed electrical activation sequences were consistent with experimentally observed patterns. Asynchronous time courses of regional strains during beats stimulated from the left or right ventricular epicardium showed good agreement with published experimental measurements in dogs using magnetic resonance imaging tagging methods. When electrical depolarization in the model was coupled to the onset of local contractile tension development by a constant time delay of 8 msec, the mean delay from depolarization to the onset of systolic fiber shortening was 14 msec. However, the delay between the onset of fiber tension and initial shortening varied significantly; it was as late as 60 msec in some regions but was also as early as −50 msec (i.e., 42 msec before depolarization) in other regions, particularly the interventricular septum during free‐wall pacing.

Conclusion: The large variation in delay times was attributable to several factors including local anatomic variations, the location of the site relative to the activation wavefront, and regional end‐diastolic strain. Therefore, we conclude that these factors, which are intrinsic to three‐dimensional ventricular function, make the regional sequence of fiber shortening an unreliable surrogate for regional depolarization or electromechanical activation in the intact ventricles. (J Cardiovasc Electrophysiol, Vol. 14, pp. S196‐S202, October 2003, Suppl.)