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Atrial fibrillation (AF) is a common cardiac arrhythmia with serious health consequences if not detected and treated early. Detecting AF using wearable devices with photoplethysmography (PPG) sensors and deep neural networks has demonstrated some success using proprietary algorithms in commercial solutions. However, to improve continuous AF detection in ambulatory settings towards a population-wide screening use case, we face several challenges, one of which is the lack of large-scale labeled training data. To address this challenge, we propose to leverage AF alarms from bedside patient monitors to label concurrent PPG signals, resulting in the largest PPG-AF dataset so far (8.5 M 30-second records from 24,100 patients) and demonstrating a practical approach to build large labeled PPG datasets. Furthermore, we recognize that the AF labels thus obtained contain errors because of false AF alarms generated from imperfect built-in algorithms from bedside monitors. Dealing with label noise with unknown distribution characteristics in this case requires advanced algorithms. We, therefore, introduce and open-source a novel loss design, the cluster membership consistency (CMC) loss, to mitigate label errors. By comparing CMC with state-of-the-art methods selected from a noisy label competition, we demonstrate its superiority in handling label noise in PPG data, resilience to poor-quality signals, and computational efficiency.

High-power, short duration (HPSD) radiofrequency ablation (RFA) is a commonly used strategy for pulmonary vein isolation (PVI).

Transseptal puncture is a necessary component of many electrophysiology and structural heart procedures. Improving this technique has broad ramifications for the overall efficiency and safety of these interventions. A new technology uses a specialized introducer wire to cross the septum with radiofrequency (RF) energy, eliminating the need for a transseptal needle and wire/needle exchanges.

The difference between the right ventricular (RV) apical stimulus–atrial electrogram (SA) interval during resetting of supraventricular tachycardia (SVT) versus the ventriculoatrial (VA) interval during SVT (ΔSA-VAapex) is an established technique for discerning SVT mechanisms but is limited by a significant diagnostic overlap.

Photoplethysmography (PPG) is a ubiquitous physiological measurement that detects beat-to-beat pulsatile blood volume changes and hence has a potential for monitoring cardiovascular conditions, particularly in ambulatory settings. A PPG dataset that is created for a particular use case is often imbalanced, due to a low prevalence of the pathological condition it targets to predict and the paroxysmal nature of the condition as well. To tackle this problem, we propose log-spectral matching GAN (LSM-GAN), a generative model that can be used as a data augmentation technique to alleviate the class imbalance in a PPG dataset to train a classifier. LSM-GAN utilizes a novel generator that generates a synthetic signal without a up-sampling process of input white noises, as well as adds the mismatch between real and synthetic signals in frequency domain to the conventional adversarial loss. In this study, experiments are designed focusing on examining how the influence of LSM-GAN as a data augmentation technique on one specific classification task - atrial fibrillation (AF) detection using PPG. We show that by taking spectral information into consideration, LSM-GAN as a data augmentation solution can generate more realistic PPG signals.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jtcvs.2008.08.036 Byline: Jiashing Yu (a), Karen L. Christman (a), Eric Chin (c), Richard E. Sievers (c), Maythem Saeed (b), Randall J. Lee (a)(c) Abbreviations: ECM, extracellular matrix; LV, left ventricular; LVID, left ventricular internal dimension; MI, myocardial infarction; MRI, magnetic resonance imaging; PBS, phosphate-buffered saline; RGD, arginine-glycine-asparagine Abstract: Various approaches to myocardial reconstruction have been developed for the treatment of congestive heart failure resulting from ischemic cardiomyopathy. Author Affiliation: (a) University of California Berkeley and University of California San Francisco Joint Bioengineering Graduate Group, Berkeley/San Francisco, Calif (b) Department of Radiology, University of California, San Francisco, Calif (c) Cardiovascular Research Institute and Department of Medicine, University of California, San Francisco, Calif Article History: Received 21 April 2008; Revised 23 July 2008; Accepted 21 August 2008 Article Note: (footnote) Research was partially supported by grants from the Nora Eccles Treadwell Foundation and Symphony Medical, Inc.

Left atrial appendage (LAA) epicardial exclusion has been associated with addressing 2 potential deleterious consequences attributed to the LAA, namely, thrombus formation and an arrhythmogenic contributor in advanced forms of atrial fibrillation. With more than 60 years of history, the surgical exclusion of the LAA has been firmly established. Numerous approaches have been used for surgical LAA exclusion including surgical resections, suture ligation, cutting and non-cutting staples, and surgical clips. Additionally, a percutaneous epicardial LAA ligation approach has been developed. A discussion of the various epicardial LAA exclusion approaches and their efficacy will be discussed, along with the salient beneficial affects on LAA thrombus formation, LAA electrical isolation and neuroendocrine homeostasis.

A total of 8 patients with junctional tachycardia (JT) were included for study. Patients with JT had a supraventricular arrhythmia that was initiated by a junctional complex without PR prolongation and episodes of atrioventricular (AV) dissociation. JT could not be initiated by pacing and occurred either spontaneously (3 patients) or with isoproterenol (5 patients). Tachycardia could be consistently terminated by either carotid sinus massage (1 patient), intravenous adenosine (2 patients), or critically timed ventricular premature complexes (3 patients). In 6 of the 8 other patients, tachycardia foci (atrial or ventricular) or mechanisms (AV node reentry) were found. Two patients underwent complete AV junctional ablation and 2 had termination of tachycardia without change in the AV conduction by perinodal application of radiofrequency lesions. AVJT appears to be due to abnormal automaticity and may be successfully ablated by application of radiofrequency energy to perinodal areas. (Am J Cardiol 1994;74:565-572)

The aim of this study was to assess the safety and efficacy of a new subxiphoid hybrid epicardial-endocardial atrial fibrillation (AF) ablation and left atrial appendage (LAA) ligation approach for the treatment of persistent AF.

Lipid profile changes in heart muscle have been previously linked to cardiac ischemia and myocardial infarction, but the spatial distribution of lipids and metabolites in ischemic heart remains to be fully investigated. We performed desorption electrospray ionization mass spectrometry imaging of hearts from in vivomyocardial infarction mouse models. In these mice, myocardial ischemia was induced by blood supply restriction via a permanent ligation of left anterior descending coronary artery. We showed that applying the machine learning algorithm of gradient boosting tree ensemble to the ambient mass spectrometry imaging data allows us to distinguish segments of infarcted myocardium from normally perfused hearts on a pixel by pixel basis. The machine learning algorithm selected 62 molecular ion peaks important for classification of each 200 μm-diameter pixel of the cardiac tissue map as normally perfused or ischemic. This approach achieved very high average accuracy (97.4%), recall (95.8%), and precision (96.8%) at a spatial resolution of ∼200 μm. In addition, we determined the chemical identity of 27 species, mostly small metabolites and lipids, selected by the algorithm as the most significant for cardiac pathology classification. This molecular signature of myocardial infarction may provide new mechanistic insights into cardiac ischemia, assist with infarct size assessment, and point toward novel therapeutic interventions.

This study hypothesized that early coupled ventricular extrastimuli (V2) stimulation might yield a more robust differentiation between atrioventricular nodal re-entrant tachycardia (AVNRT) and atrioventricular re-entrant tachycardia (AVRT).

This study sought to determine how many patients with atrial fibrillation (AF) are not treated with oral anticoagulants (OAC) due to a high risk of bleeding and to characterize their risk of ischemic stroke in a real-world setting.

Inappropriate sinus tachycardia (IST) is defined as resting heart rate >100 bpm and average 24-h heart rate >90 bpm. It is associated with distressing symptoms and significant loss of quality of life. Drugs are not effective in symptom control of IST in up to 30% of patients. Catheter ablation of sinus node has a high recurrence rate and the complications are significant. Recently, a novel hybrid sinus node sparing ablation approach for IST was described.

Introduction:Transseptal puncture is a necessary component of many electrophysiology and structural heart procedures. A new technology utilizes a specialized introducer wire to cross the septum with radiofrequency (RF) energy, eliminating the need for a transseptal needle and wire/needle exchanges. The RF wire technique, however, has not been evaluated in a randomized trial.Methods:The Wire Instrumentation with Radiofrequency Energy to Impact Transseptal puncture (WIRE IT, NCT04645342) study was an investigator-initiated and designed trial that enrolled individuals ≥18 years of age undergoing double transseptal puncture for atrial fibrillation or left atrial flutter ablation. Participants were randomized to a transseptal approach with either a RF needle (NRG Transseptal Needle, Baylis Medical) or RF wire (Versacross RF Wire, Baylis Medical). The primary outcome was time to achieve first transseptal puncture. Timing was started at insertion of the guidewire into the short femoral vein sheath and was stopped once the transseptal sheath was positioned in the left atrium andthe dilator and guidewire were removed. Secondary outcomes included second and combined transseptal puncture time, fluoroscopy time, number of equipment exchanges, and complications.Results:A total of 75 participants were enrolled between November 30, 2020 and February 2, 2022 (36 RF needle, 39 RF wire). No crossovers occurred. Randomization to the RF wire resulted in a statistically significant reduction in first transseptal time compared to the RF needle (Figure). Second and combined transseptal times and number of equipment exchanges were also reduced with the RF wire. One participant in the RF needle group experienced transient AV block due to mechanical trauma. There were no complications in the RF wire group.Conclusions:The RF wire technique resulted in faster time to transseptal puncture and fewer equipment exchanges compared to an RF needle with no difference in complications.

This study sought to assess long-term clinical outcomes in adults with nonvalvular atrial fibrillation (AF) who are ineligible for oral anticoagulation therapy and underwent left atrial appendage (LAA) ligation with the Lariat device.

There is a great need for delivery strategies capable of efficiently localizing drugs to the damaged myocardium that do not require direct intramyocardial injection of therapeutic molecules. In the work discussed here, we exploited the myocardium-specific upregulation of matrix metalloproteinases (MMPs) that occurs during myocardium remodeling by designing a micellar vehicle containing an MMP-targeting peptide (MMP-TP). The binding of MMP-TP to MMP was evaluated with purified MMP-2 protein and U-937 cells induced to overexpress MMP. Inhibition of MMP-2 activity was not observed in the presence of unmodified micelles but was pronounced at a 5 mol % MMP-TP ligand density. In a FACS analysis, MMP-TP micelles containing 5 mol % of the MMP-targeting peptide showed ∼10-fold higher binding to activated U937 cells than plain micelles and micelles containing a control peptide with two amino acid replacements. MMP-TP-micelles and plain micelles were injected intravenously into C57BL/6 mice 1, 3, and 7 days after the induction of a myocardial infarction (MI). Immunohistochemistry performed on heart tissue sections revealed that MMP-TP-micelles colocalize with both MMP and infiltrating macrophages. MMP-TP micelles showed significantly enhanced accumulation to the necrotic area of the heart after MI on days 3 and 7 when compared to plain micelles and negative control peptide micelles. This is coincident with the measured temporal profile of MMP gene expression in the heart after MI. These results suggest that MMP-TP micelles are candidates for the development of targeted regenerative heart therapeutics because of their ability to target the infarcted myocardium in a MMP dependent manner.

The study tested the hypothesis that augmentation of the left ventricular (LV) wall thickness with direct intramyocardial injections of alginate hydrogel implants (AHI) reduces LV cavity size, restores LV shape, and improves LV function in dogs with heart failure (HF).

Heart failure continues to be a major health care concern with relatively few options for severely advanced heart failure patients. The hallmark of heart failure is the progressive dilatation of the left ventricle, thinning of the left ventricular wall leading to increased wall stress and increased myocardial oxygen consumption. Applying Laplace's law to the failing dilated ventricle, left ventricular augmentation utilizes a tissue engineering strategy to increase wall thickness and reduce chamber diameter, resulting in a decrease in wall stress and improved left ventricular function. A review of the rationale for an in situ tissue engineering approach for this treatment of heart failure and early clinical results of the Algisyl-LVR™program are presented.

Surgical ligation of the left atrial appendage (LAA) has been shown to be an effective alternative to warfarin therapy in patients with atrial fibrillation. A novel catheter-based approach for LAA ligation was evaluated for safety and effectiveness in a canine model.

Introduction:Electrical isolation of the left atrial appendage (LAA) using percutaneous epicardial ligation may improve catheter ablation outcomes for non-paroxysmal atrial fibrillation (AF) patients. Little is known regarding the cost effectiveness of this procedure.Hypothesis:We hypothesized that cost-effectiveness between pulmonary vein isolation (PVI) + LAA epicardial ligation using a percutaneous LARIAT®Suture Delivery Device would be cost effective (CE) compared to PVI alone over 5 years.Methods:A Markov model simulated outcomes for a population with annual stroke risk of 4.6% (CHA2DS2-VASc score 3). Model inputs for procedure efficacy, stroke and bleed events, health utility, and event costs were estimated from literature. Procedure costs from Medicare rates were used. The model had a 5-year time-horizon and US payer perspective. Univariate and probabilistic sensitivity analyses (PSA) were performed. Outcomes were health care costs and quality-adjusted life-years (QALYs). In the base case, PVI + LAA ligation efficacy from published studies was 67% after 1-year, with an estimated 25% oral anticoagulant (OAC) utilization in PVI + LAA ligation patients in normal sinus rhythm 13-60 months after the index procedure. Cost effectiveness thresholds were evaluated with alternative PVI + LAA ligation efficacy and OAC utilization rates, including 1-year PVI + LAA ligation efficacies of 67%, 70%, 75%, and 80% and OAC utilization of 20-60%.Results:In the base case, PVI + LAA ligation had a mean 5-year cost of $72,865 with 3.25 QALYs and PVI alone had mean cost of $69,936 with 3.19 QALYs. The incremental cost-effectiveness ratio was $46,716; PVI + LAA ligation was CE at $50,000 per QALY gained. In PSA, 64% and 82% of simulations were CE at $50,000 and $100,000 per QALY gained, respectively. In various scenarios, procedure efficacy of 75% combined with OAC utilization of 50% or below yielded CE at $50,000 per QALY gained. Reduction of OAC utilization to 30% yielded CE at $50,000 per QALY gained, regardless of efficacy.Conclusions:In the base case, PVI + LAA ligation was CE at $50,000 per QALY gained when compared to PVI alone. The CE threshold for efficacy was 75% and OAC utilization was 30%. Cost savings were driven by reductions in OAC use and increased efficacy.

We have developed a robust rat model of myocardial infarction (MI). Here we describe the step-by-step protocol for creating an ischemia-reperfusion rat model of MI. We also describe how to deliver therapeutic injections of mesenchymal stem cells (MSCs) together with fibrin, to show an application of this model. In addition, to confirm the presence of fibrin and cells in the infarct, visualization of MSCs and fibrin by histological techniques are also described. The ischemia-reperfusion MI model can be modified and generalized for use with various injectable polymers, cell types, drugs, DNA and combinations thereof. The model can be created in 7 days or less, depending on the timing of therapeutic intervention.

Novel strategies by which to repair ischemic myocardium after myocardial infarction include the use of three-dimensional polymer scaffolds. A comparative study was carried out to assess the therapeutic potential of fibrin, collagen I, and Matrigel as injectable biopolymers for repair after myocardial infarction. Using a rat model of left coronary artery occlusion followed by reperfusion, local injection of the biopolymers into the infarct zone yielded significantly higher levels of capillary formation, when compared with the saline control group, at 5 weeks posttreatment. However, the degree of angiogenesis was not significantly different among the biopolymers. In addition, the collagen biopolymer significantly enhanced infiltration of myofibroblasts into the infarct area when compared with the control group. The results of this study highlight the potential clinical benefit of these biopolymers as injectable scaffolds or cell delivery vehicles to the infarct zone after infarction.

Current efforts in cardiac tissue engineering center around the use of scaffolds that deliver cells to the epicardial surface. In this study, we examined the effects of fibrin glue as an injectable scaffold and wall support in ischemic myocardium. The left coronary artery of rats was occluded for 17 min, followed by reperfusion. Echocardiography was performed 8 days after infarction. One to 2 days later, either 0.5% bovine serum albumin (BSA) in phosphate-buffered saline, fibrin glue alone, skeletal myoblasts alone, or skeletal myoblasts in fibrin glue were injected into the ischemic left ventricle. Echocardiography was again performed 5 weeks after injection. The animals were then sacrificed and the hearts were fresh frozen and sectioned for histology and immunohistochemistry. Both the fractional shortening (FS) and infarct wall thickness of the BSA group decreased significantly after 5 weeks (p = 0.0005 and 0.02, respectively). In contrast, both measurements for the fibrin glue group, cells group, and cells in fibrin glue group did not change significantly (FS: p = 0.18, 0.89, and 0.19, respectively; wall thickness: p = 0.40, 0.44, 0.43, respectively). Fibrin glue is capable of preserving infarct wall thickness and cardiac function after a myocardial infarction in rats and may be useful as a biomaterial scaffold for myocardial cell transplantation.

Objective:Myocardial infarct expansion and subsequent left ventricular remodeling are associated with increased incidence of congestive failure and mortality. Collagen is known to denature and contract when heated above 65°C. We therefore tested the hypothesis that radio frequency heating of myocardial infarct tissue with application of a restraining patch causes a sustained reduction in myocardial infarct area and left ventricular volume. Methods:Thirteen male Dorset sheep underwent surgical coronary artery ligation. At least 14 weeks later, animals were randomized to either radio frequency infarct heating (95°C) with application of a restraining patch or a sham operation. Before treatment, after treatment, and 10 weeks later, left ventricular volume was measured with transdiaphragmatic echocardiography and myocardial infarct area was measured with an array of sonomicrometry crystals. Results:Radio frequency infarct heating causes an acute decrease of 34% (–215 ± 82 mm2; P= .0002) in infarct area at end-diastole that is maintained at 10 weeks (–144 ± 79 mm2; P= .0002). Radio frequency infarct heating causes a downward trend in end-diastolic left ventricular volume measured by echocardiography of 20% (–15.7 ± 6.3 mL; P= no significant difference) and end-systolic left ventricular volume of 32% (–17.1 ± 9.8 mL; P= .09), which are significantly decreased at 10 weeks (–13.6 ± 22.3 mL; P= .007 and –15.3 ± 21.9 mL; P= .008, respectively). Radio frequency infarct heating causes an acute improvement in systolic function (P< .001), a sustained increase in left ventricular ejection fraction (+0.11%; P= .06), and preserved stroke volume. Conclusion:Radio frequency heating of chronic left ventricular myocardial infarct causes a sustained reduction in infarct area and left ventricular volume. This technique may beneficially reverse infarct expansion and left ventricular remodeling after myocardial infarction. (J Thorac Cardiovasc Surg 2000;119:1194-204)

The actin-dependent ATPase activity of Dictyostelium myosin II filaments is regulated by phosphorylation of the regulatory light chain. Four deletion mutant myosins which lack different parts of subfragment 2 (S2) showed phosphorylation-independent elevations in their activities. Phosphorylation-independent elevation in the activity was also achieved by a double point mutation to replace conserved Glu932 and Glu933 in S2 with Lys. These results suggested that inhibitory interactions involving the head and S2 are required for efficient regulation. Regulation of wild-type myosin was not affected by copolymerization with a S2 deletion mutant myosin in the same filaments. Furthermore, the activity linearly correlated with the fraction of phosphorylated molecules in wild-type filaments. These latter two results suggest that the inhibitory head-tail interactions are primarily intramolecular.

OBJECTIVES

OBJECTIVES

Despite high efficacy, electrical defibrillation shocks can fail or ventricular fibrillation (VF) is reinitiated after the application of the initial shock. The goal of this study was to determine whether [Ca2+]ioverload, induced by VF itself, can cause failed electrical defibrillation and post-shock reinitiation of VF. For this purpose, we simultaneously measured [Ca2+]itransients (assessed by indo-1 fluorescence) and defibrillation energies (assessed by a modified implantable cardioverter defibrillator) in intact perfused rat hearts during pacing-induced sustained VF (10 min) in the absence of ischemia. We found that increasing [Ca2+]iduring VF (by increasing [Ca2+]ofrom 3 to 6 mm) increased the defibrillation threshold (DFT) from 1.9±0.6 to 3.5±0.5 J/g (P<0.05) and also increased the total defibrillation energy (TDE) required for stabilization of sinus rhythm from 15.6±7.7 to 48.6±7.42 J/g (P<0.05). In addition, both DFT and TDE correlated linearly with [Ca2+]i(r=0.69 and 0.83,P<0.05). Furthermore, shortening the duration of VF from 10 to 1.5 min tended to limit [Ca2+]ioverload and decreased TDE. Finally, all successful defibrillation shocks led to a sudden reduction of VF-induced [Ca2+]ioverload (−115±3%). In contrast, failed shocks did not alter [Ca2+]i. Incomplete reduction of [Ca2+]ioverload after initially successful shocks were often followed by synchronized spontaneous [Ca2+]ioscillations and subsequent reinitiation of VF. In conclusion, the present study showed for the first time that VF-induced [Ca2+]ioverload can cause failed electrical defibrillation and post-shock reinitiation of VF. Because VF inevitably causes [Ca2+]ioverload, this finding might be a crucial mechanism of failed defibrillation and spontaneous reinitiation of VF.

Vulnerability to ventricular fibrillation (VF) is frequently evaluated by VF threshold, a variable which may not be free of confounding factors and which may not be sensitive to all factors contributing to vulnerability. Therefore, we tested whether VF threshold determination affects intracellular free Ca2+([Ca2+]i) and whether VF thresholds are sensitive to changes in [Ca2+]i. For this purpose, we analysed [Ca2+]iby surface fluorometry and indo-1 in intact perfused rat hearts undergoing VF threshold determination by a single pulse method and tested whether such thresholds are lowered by increased [Ca2+]i. Additionally, we sought to determine the importance of Ca2+for the vulnerability to VF under nonischemic conditions. For this purpose, we measured VF thresholds by a new pulse number method which scanned the vulnerable period by an increasing number of sequential pulses at increasing prematurity but constant intensity. We found that VF threshold determination by a single pulse method led to a rise in systolic [Ca2+]i. However, this rise does not perturb VF threshold interpretation because such thresholds were insensitive to changes in [Ca2+]i. Nevertheless, [Ca2+]iis of importance for the vulnerability to VF under nonischemic conditions because the number of VF-free tolerated premature pulses was dependent on [Ca2+]i. This relationship may only be detectable if evaluated by sequential pulse methods. These findings suggest that the method of VF threshold determination may be crucial for the result of studies testing Ca2+antagonists or situations of altered [Ca2+]iand could explain controversial results of VF threshold studies testing Ca2+antagonists by varying methods.

Objectives. The purpose of this study was to evaluate the efficacy and safety of radiofrequency catheter ablation for the treatment of supraventricular tachycardias in an elderly (≥70 years of age) group of patients.

Objectives. The purpose of this study was 1) to investigate the efficacy and safely of radiofrequency energy catheter ablation as curative treatment for idiopathic tachycardia of both left and right ventricular origin, and 2) to compare the usefulness of different methods used to map the site of origin of idiopathic veotricular tachycardia.

Objectives. We sought to use intracardiac echocardiography (ICE) to identify the anatomic origin of focal right atrial tachycardias and to define their relation with the crista terminalis (CT).

This study sought to construct an algorithm to differentiate left atrial from right atrial tachycardia foci on the basis of surface electrocardiograms (ECGs).

The cycle length dependence of the action potential duration and the effective refractory period of the right ventricular endocardium were investigated in 24 patients undergoing electrophysiologic studies for suspected ventricular tachycardia. The action potential duration at 90% repolarization and the effective refractory period at twice diastolic threshold strength were measured at the same catheter site at steady state cycle lengths of 350 to 600 ms. Both measurements decreased linearly with decreasing cycle length, maintaining a parallel relation. When the relation between action potential duration and effective refractory period was expressed as the effective refractory period-action potential duration difference, nearly constant values (range −12 to −15 ms) were obtained at all cycle lengths.

Atrioventricular (AV) block is a useful substrate for the study of cardiac physiology. The objective of this investigation was to develop a straightforward and reproducible model of permanent AV block in rats. Working through a sternotomy, we used an epicardial fat pad between the aortic root and the right atrial wall of the rat as a landmark for the site for injection of 70% ethanol (5–10 μl) into the myocardium 3 mm below the epicardial surface. Stable, complete heart block was produced in 23 of 28 rats (82%) with a success rate of 100% in the last 16 rats of the series. Saline injection produced no heart block in 15 rats. A separate group of 14 animals was allowed to recover. Chronic heart block was achieved in all ethanol-injected animals for up to 7 days before death. The survival rate in the recovered rats was 90% in the ethanol-injected group and 100% in the saline-injected control group. Acute hemodynamic changes following the production of heart block consisted of an increase in central venous pressure, a decrease in systolic blood pressure, a decrease in left ventricular pressure, and a decrease in change in pressure over time. Chronic hemodynamic changes demonstrated a return to baseline of the central venous pressure, a persistent decrease in systolic blood pressure, and a decrease in left ventricular pressure. After the rats were killed and the hearts were dissected, discrete areas of myocardial damage were identified histologically in the atrial septum near the AV conduction axis tissue in the ethanol-injected hearts. Complete heart block was associated only with lesions extending into the specialized muscle of the AV node or His bundle. Focal mild hemorrhage, inflammation, and damaged myocardial fibers were observed in the acute stage, whereas healing lesions were characterized by granulation tissue and fibrosis replacing conduction tissue. The simple technique described provides a reproducible model for permanent, complete heart block and the study of cardiac function.

Objectives. In this study, we propose a new algorithm for accessory atrioventricalar pathway localization using a 12-lead electrocardiogram (ECG).

Objectives. Using a standardized induction protocol, we investigated the mechanism of initiation of atrial flutter, before ablation, to determine the site of initiating unidirectional block and to test the hypothesis that the direction of rotation of atrial flutter depends on the pacing site from which it initiates.

Conventional myosin (‘myosin II’) is a major component of the cytoskeleton in a wide variety of eukaryotic cells, ranging from lower amoebae to mammalian fibroblasts and neutrophils. Gene targeting technologies available in the Dictyostelium discoideum system have provided the first genetic proof that this molecular motor protein is essential for normal cytokinesis, capping of cell surface receptors, normal chemotactic cell locomotion and morphogenetic shape changes during development. Although the roles of myosin in a variety of cell functions are becoming clear, the mechanisms that regulate myosin assembly into functional bipolar filaments within cells are poorly understood. Dic-tyostelium is currently the only system where mutant forms of myosin can be engineered in vitro, then expressed in their native context in cells that are devoid of the wild-type isoform. We have utilized this technology in combination with nested truncation and deletion analysis to map domains of the myosin tail necessary for in vivo and in vitro filament assembly, and for normal myosin heavy chain (MHC) phosphorylation. This analysis defines a region of 35 amino acids within the tail that is critical for filament formation both for purified myosin molecules and for myosin within the in vivo setting. Phosphorylation analysis of these mutants in intact cytoskeletons demonstrates that the carboxy-terminal tip of the myosin heavy chain is required for complete phosphorylation of the myosin tail.

This study sought to identify acute changes in human atrial electrophysiology during alcohol exposure.

Repairing cardiac tissue remains one of the most challenging goals in tissue engineering. Here, we discuss ways whereby we sought to treat myocardial infarctions using extracellular-matrix derived peptides. Using an ischemia/reperfusion myocardial infarction rodent model, we targeted these extracellular matrix-derived peptides to the myocardial infarct site and were able to induce angiogenesis and alter the negative remodeling seen after an acute myocardial infarction. Our results indicate a potentially new strategy for repairing damaged tissue.

Ischemic heart disease represents the leading cause of death worldwide. Heart failure following myocardial infarction (MI) is associated with severe fibrosis formation and cardiac remodeling. Recently, injectable hydrogels have emerged as a promising approach to repair the infarcted heart and improve heart function through minimally invasive administration. Here, a novel injectable human amniotic membrane (hAM) matrix is developed to enhance cardiac regeneration following MI. Human amniotic membrane is isolated from human placenta and engineered to be a thermoresponsive, injectable gel around body temperature. Ultrasound‐guided injection of hAM matrix into rat MI hearts significantly improves cardiac contractility, as measured by ejection fraction (EF), and decrease fibrosis. The results of this study demonstrate the feasibility of engineering as an injectable hAM matrix and its efficacy in attenuating degenerative changes in cardiac function following MI, which may have broad applications in tissue regeneration. Injectable hydrogels have emerged as a promising and attractive therapeutic strategy to halt progressive cardiac dysfunction following myocardial infarction (MI), through minimally invasive and localized administration. This study demonstrates that human placental tissue can be decellularized and engineered as the injectable thermoresponsive bioactive gel to significantly promote cardiac regeneration in a rat MI model.

Direct injection of marrow cells into injured myocardium improves cardiac function, however, repair may be limited by the number of stem cells that home and persist in the injured myocardium. Using nude rats that received a 17 min transient ligation of their left anterior descending artery, we tested whether anti-CD3 activated human T cells (ATC), G-CSF primed peripheral blood mononuclear cells (G-PBMC), or G-CSF primed purified CD34+ cells would target MI-specific injury antigens ICAM-1 or rat myosin light chain (MLC) when injected intra-jugularly 48 hrs after myocardial injury. ATC, G-PBMC, or CD34+ cells were armed (50 ng/106 cells) with anti-CD3 x anti-rat ICAM-1 or anti-CD45 x anti-MLC. Nude rats were euthanized at 24 hours or 5 weeks after treatment and hearts were frozen, sectioned, fixed, and stained accordingly. In a pilot experiment, ATC armed with OKT3 x anti-ICAM were detected at the MI sites by Cy3 staining but not in the adjacent normal myocardium 24 hrs after infusion; rats given unarmed ATC or ATC armed with anti-CD3 x anti-CD20 (irrelevant BiAb) did not stain. High numbers of cells in the MIs in rats given anti-human CD45 x anti-rat MLC-armed G-PBMC stained positive by tyramide-amplified IHC for the mouse IgG or human CD45 cells. Human cells stained for HLA-DR (>5000 cells/injured HPF) in MIs of rats treated with BiAb-armed cells compared to unarmed-treated rats (<500/injured HPF) by 24 hrs post-infusion. By 5 weeks, the persistent human marker was HLA-Class I in the MIs whereas only a few HLA-Class II cells remained; the number of Class I cells in the MIs of rats treated with BiAb-armed cells (45.3±4.9 Class I+ cells/HPF) was significantly greater compared to MIs of rats treated with unarmed cells (25.9±1.7 Class I+ cells/HPF). In order to determine whether Isolex column-purified CD34+ cells (99% CD34, 70% CD33, and negative for CD-4,-7,-10,-16,-19,-20, and -23) obtained from G-PBMC would lead to cells expressing Class I and troponin, actin, or VE-cadherin, the hearts from rats that received CD34+ cells alone (3 rats) or CD34+ cells armed with anti-CD45 x anti-MLC (6 rats) were harvested 5 weeks after the infusion, fresh frozen, and double stained for each antigen-pair. These double stains as well as confocal images on the same slides show evidence for myocytes staining for human Class I and the respective cardiac antigens. After 5 weeks, ECHOS showed that the fractional shortening of the armed group was significantly improved compared to the unarmed group (0.33 ± 0.06 vs 0.19 ± 0.03; P = 0.02). Additionally, average LV size of the armed group was significantly less dilated compared to the unarmed group (0.47 ± 0.12 vs 0.67 ± 0.04; p = 0.04). Our studies show that arming CD34+ cells with BiAbs can target SC to MIs. The targeted SC express surface markers for human Class I and the muscle proteins troponin, actin, and cadherin; ECHO data suggest improved cardiac function. Studies are underway to maximize BiAb-armed CD34+ cell delivery to provide optimal recovery of cardiac function and to further characterize the cells that develop from the CD34+ cells.