Michael C. Fishbein

Mesenchymal Stem Cell Injection Induces Cardiac Nerve Sprouting and Increased Tenascin Expression in a Swine Model of Myocardial Infarction

Introduction: Mesenchymal stem cell (MSC) transplantation is a promising technique to improve cardiac function. Whether MSC can increase cardiac nerve density and contribute to the improved cardiac function is unclear.

New Perspectives on the Role of Autonomic Nervous System in the Genesis of Arrhythmias

Sudden cardiac death (SCD) is a major cause of morbidity and mortality in patients with coronary artery diseases and myocardial infarction (MI). There is a circadian variation of the frequency of SCD. Beta‐blocker therapy significantly reduces the incidence of SCD after MI. These clinical observations suggest a close association between ventricular arrhythmia and sympathetic activity in patients with MI. Following injury, peripheral nerves undergo Wallerian degeneration, which may be followed by neurilemma cell proliferation and axonal regeneration (nerve sprouting), resulting in sympathetic hyperinnervation. It is possible that the increased innervation after myocardial injury may result in increased sympathetic nerve density, which in turn increases the propensity for cardiac arrhythmia. While this Nerve Sprouting Hypothesis seemed to be intuitive, there was no experimental proof of a causal link between sympathetic nerve sprouting and arrhythmogenesis. We therefore performed several studies to determine the relationship between nerve sprouting and cardiac arrhythmia. We also performed direct sympathetic nerve recording in an animal model of SCD. We found that cardiac sympathetic nerves are highly plastic. In addition to MI and rapid pacing, nerve sprouting and heterogeneous sympathetic hyperinnervation may also be induced by radiofrequency ablation, hypercholesterolemia, and stem cells transplantation. The coexistence of denervated and hyperinnervated area in the diseased myocardium could result in increased electrophysiological heterogeneity during sympathetic activation, leading to ventricular arrhythmia and SCD.

Modulation of QT interval by cardiac sympathetic nerve sprouting and the mechanisms of ventricular arrhythmia in a canine model of sudden cardiac death

QT Interval and Sudden Cardiac Death. Introduction: We previously reported that there is a high incidence of sudden cardiac death (SCD) in dogs with myocardial infarction (MI), complete AV block (CAVB), and nerve growth factor (NGF) infusion to the left stellate ganglion (LSG). Whether or not QT interval prolongation underlines the mechanism of SCD was unclear.

Catheter Ablation of Right Ventricular Outflow Tract Tachycardia: Value of Defining Coronary Anatomy

Introduction: Thermal damage to coronary arteries during catheter ablation has been previously reported. Coronary artery damage during LV outflow tract ventricular tachycardia is well recognized. However, the relationship of the coronary arteries to the RV outflow tract during catheter ablation has not been delineated. The purpose of this study was to define the relationship between the RV outflow tract and the coronary arteries utilizing arteriography, echocardiography, CT angiography, and gross anatomic pathology.

The mechanisms of atrial fibrillation

In this article we have reviewed the mechanisms of atrial fibrillation (AF) with special emphasis on the thoracic veins. Based on a number of features, the thoracic veins are highly arrhythmogenic. The pulmonary vein (PV)‐left atrial (LA) junction has discontinuous myocardial fibers separated by fibrotic tissues. The PV muscle sleeve is highly anisotropic. The vein of Marshall (VOM) in humans has multiple small muscle bundles separated by fibrosis and fat. Insulated muscle fibers can promote reentrant excitation, automaticity, and triggered activity. The PV muscle sleeves contain periodic acid‐Schiff (PAS)‐positive large pale cells that are morphologically reminiscent of Purkinje cells. These special cells could be the sources of focal discharge. Antiarrhythmic drugs have significant effects on PV muscle sleeves both at baseline and during AF. Both class I and III drugs have effects on wavefront traveling from PV to LA and from LA to PV. Separating the thoracic veins and the LA with ablation techniques also prevents PV‐LA interaction. By reducing PV‐LA interaction, pharmacological therapy and PV isolation reduce the activation rate in PV, intracellular calcium accumulation, and triggered activity. Therefore, thoracic vein isolation is an important technique in AF control. We conclude that thoracic veins are important in the generation and maintenance of AF.

Heart Failure Decreases Nerve Activity in the Right Atrial Ganglionated Plexus

Reduced Vagal Control in Heart Failure.

Relation Between Cellular Repolarization Characteristics and Critical Mass for Human Ventricular Fibrillation

Critical Mass for Human Ventricular Fibrillation. Introduction: The critical mass for human ventricular fibrillation (VF) and its electrical determinants are unclear. The goal of this study was to evaluate the relationship between repolarization characteristics and critical mass for VF in diseased human cardiac tissues.

Demonstration of Electrical and Anatomic Connections Between Marshall Bundles and Left Atrium in Dogs: Implications on the Generation of P Waves on Surface Electrocardiogram

Marshall Bundle and P Wave. Introduction: The muscle bundles within the ligament of Marshall (LOM) are electrically active. The importance of these muscle bundles (Marshall bundle [MB]) to atrial activation and the generation of the ECG P wave is unclear.

Low-Affinity Nerve Growth Factor Receptor p75NTR Immunoreactivity in the Myocardium with Sympathetic Hyperinnervation

Introduction: We previously demonstrated the relationship between sympathetic nerve density in myocardium and the occurrences of ventricular arrhythmia. Nerve growth factor (NGF) regulates myocardial sympathetic innervation. However, it is unclear whether the NGF high‐affinity receptor tyrosine kinase A (TrkA) and the NGF low‐affinity receptor p75NTR are altered in the state of sympathetic hyperinnervation in the heart. The aim of this study was to determine the density and location of TrkA and p75NTR in canine ventricles with sympathetic hyperinnervation.

Spontaneous atrial fibrillation initiated by tyramine in canine atria with increased sympathetic nerve sprouting.

Sympathetic Activation and Atrial Fibrillation.