Determinants of outcome impact of vein of Marshall ethanol infusion when added to catheter ablation of persistent atrial fibrillation: A secondary analysis of the VENUS randomized clinical trial.

Background: The Vein of Marshall Ethanol for Untreated Persistent AF (VENUS) trial demonstrated that adding vein of Marshall (VOM) ethanol infusion to catheter ablation (CA) improves ablation outcomes in persistent atrial fibrillation (AF). There was significant heterogeneity in the impact of VOM ethanol infusion on rhythm control.

Objective: The purpose of this study was to assess the association between outcomes and (1) achievement of bidirectional perimitral conduction block and (2) procedural volume.

Effect of Catheter Ablation With Vein of Marshall Ethanol Infusion vs Catheter Ablation Alone on Persistent Atrial Fibrillation: The VENUS Randomized Clinical Trial.

Importance: Catheter ablation of persistent atrial fibrillation (AF) has limited success. Procedural strategies beyond pulmonary vein isolation have failed to consistently improve results. The vein of Marshall contains innervation and AF triggers that can be ablated by retrograde ethanol infusion.

Vein of Marshall ethanol infusion for persistent atrial fibrillation: VENUS and MARS clinical trial design.

Background: Although pulmonary vein isolation (PVI) is effective in the treatment of paroxysmal atrial fibrillation (AF), its success rates in persistent AF are suboptimal. Ablation strategies to improve outcomes including additional lesions beyond PVI have not consistently shown benefit. Recurrence as perimitral flutter (PMF) is a common form of ablation failure.

Macrophage bone morphogenic protein receptor 2 depletion in idiopathic pulmonary fibrosis and Group III pulmonary hypertension.

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology. The development of pulmonary hypertension (PH) is considered the single most significant predictor of mortality in patients with chronic lung diseases. The processes that govern the progression and development of fibroproliferative and vascular lesions in IPF are not fully understood.

Altered Hypoxic-Adenosine Axis and Metabolism in Group III Pulmonary Hypertension.

Group III pulmonary hypertension (PH) is a highly prevalent and deadly lung disorder with limited treatment options other than transplantation. Group III PH affects patients with ongoing chronic lung injury, such as idiopathic pulmonary fibrosis (IPF). Between 30 and 40% of patients with IPF are diagnosed with PH.

Hypoxia-induced deoxycytidine kinase contributes to epithelial proliferation in pulmonary fibrosis.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a deadly lung disease with few therapeutic options. Apoptosis of alveolar epithelial cells, followed by abnormal tissue repair characterized by hyperplastic epithelial cell formation, is a pathogenic process that contributes to the progression of pulmonary fibrosis. However, the signaling pathways responsible for increased proliferation of epithelial cells remain poorly understood.

Large cardiac tumor managed with resection and two ventricular assist devices.

Symptomatic cardiac tumors can lead to a rapid clinical deterioration and death. Prompt surgical resection is ideal in this situation as it is the only proven treatment to date. We report the radical resection of a large malignant cardiac tumor that obstructed the right ventricular outflow tract.

Adenosine A2B receptor and hyaluronan modulate pulmonary hypertension associated with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide. The development of pulmonary hypertension (PH) in patients with COPD is strongly associated with increased mortality. Chronic inflammation and changes to the lung extracellular matrix (ECM) have been implicated in the pathogenesis of COPD, yet the mechanisms that lead to PH secondary to COPD remain unknown.

Hypoxia-induced deoxycytidine kinase expression contributes to apoptosis in chronic lung disease.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent inflammation and tissue remodeling and is a leading cause of death in the United States. Increased apoptosis of pulmonary epithelial cells is thought to play a role in COPD development and progression. Identification of signaling pathways resulting in increased apoptosis in COPD can be used in the development of novel therapeutic interventions.

Superior mesenteric artery mycotic aneurysm in patients with left ventricular assist device support and intravenous drug abuse.

Mycotic aneurysm of the superior mesenteric artery (SMA) is one of the complications associated with infective endocarditis. However, there are no previous case reports in the literature describing mycotic SMA aneurysm after left ventricular assist device (LVAD) implantation. We describe the case of a 31-year-old male diagnosed with congestive heart failure due to nonischemic dilated cardiomyopathy who underwent LVAD implantation for bridge to heart transplantation.

A guidance channel seeded with autologous Schwann cells for repair of cauda equina injury in a primate model.

Background/objective: To evaluate an implantable guidance channel (GC) seeded with autologous Schwann cells to promote regeneration of transected spinal nerve root axons in a primate model.

Methods: Schwann cells were obtained from sural nerve segments of monkeys (Macaca fascicularis; cynomolgus). Cells were cultured, purified, and seeded into a PAN/PVC GC.

Demyelination and Schwann cell responses adjacent to injury epicenter cavities following chronic human spinal cord injury.

The natural history of post-traumatic demyelination and myelin repair in the human spinal cord is largely unknown and has remained a matter of speculation. A wealth of experimental studies indicate that mild to moderate contusive injuries to the mammalian spinal cord evolve into a cavity with a preserved rim of white matter in which a population of segmentally demyelinated axons persists. It is believed that such injured axons have abnormal conduction properties.

The effect of surgically implanted bullet fragments on the spinal cord in a rabbit model.

Background: Whether or not to remove bullets or bullet fragments from the spinal column of a neurologically intact patient has been a subject of continual debate. The controversy is due in part to a lack of information about the long-term effects of bullet fragments on spinal cord tissue. Although many studies have demonstrated the toxic effects of metal fragments on brain tissue, to our knowledge no one has evaluated the effects of the metals contained in commercially available bullets on spinal cord tissue.

Embryonic cord transplants in peripheral nerve restore skeletal muscle function.

The rapid atrophy of skeletal muscle after denervation severely compromises efforts to restore muscle function. We have transplanted embryonic day 14-15 (E14-E15) ventral spinal cord cells into adult Fischer rat tibial nerve stump to provide neurons for reinnervation. Our aim was to evaluate medial gastrocnemius reinnervation physiologically because this transplant strategy will only be effective if the reinnervated muscle contracts, generates sufficient force to induce joint movement, and is fatigue resistant enough to shorten repeatedly.

Density dependent regulation of human Schwann cell proliferation.

Cessation of division is prerequisite for Schwann cell differentiation but regulation of this critical function is poorly understood. Heregulin/forskolin-induced growth of human Schwann cells (HSCs) in vitro was found to be strongly regulated by cell density and thus could model some aspects of negative growth-regulation in vivo. To better understand this phenomenon, the production of an autocrine growth-inhibitor and the role of contact-inhibition were investigated.

Long-Term Culture of Lobster Central Ganglia: Expression of Foreign Genes in Identified Neurons.

The ventral nerve cords of lobsters (Homarus americanus) can be cultured in vitro for at least 7 weeks. Over this period, neurons maintain their normal electrophysiological features and continue, among other measures of neuronal health, to synthesize RNA and proteins. One application of this culture system is demonstrated: the manipulation of gene expression in identified neurons.

The changes in human spinal sympathetic preganglionic neurons after spinal cord injury.

We have applied conventional histochemical, immunocytochemical and morphometric techniques to study the changes within the human spinal sympathetic preganglionic neurons (SPNs) after spinal cord injury. SPNs are localized within the intermediolateral nucleus (IML) of the lateral horn at the thoraco-lumbar level of the spinal cord and are the major contributors to central cardiovascular control. SPNs in different thoracic segments in the normal spinal cord were similar in soma size.

Schwann cells genetically modified to secrete human BDNF promote enhanced axonal regrowth across transected adult rat spinal cord.

The infusion of BDNF and NT-3 into Schwann cell (SC) grafts promotes regeneration of brainstem neurones into the grafts placed in adult rat spinal cord transected at T8 (Xu et al., 1995b). Here, we compared normal SCs with SCs genetically modified to secrete human BDNF, grafted as trails 5 mm long in the cord distal to a transection site and also deposited in the transection site, for their ability to stimulate supraspinal axonal regeneration beyond the injury.

Human sympathetic preganglionic neurons and motoneurons retrogradely labelled with DiI.

The retrograde tracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) was used to label sympathetic preganglionic neurons (SPN) and motoneurons (MN) in postmortem human spinal cord. Seven months after microinjection of DiI into the ventral part of spinal thoracic segments T4 and T8, DiI-labelled neurons were identified and analyzed. Cryostat sections of spinal cord were prepared for light microscopy, while vibratome sections were analyzed using confocal microscopy.

The ability of human Schwann cell grafts to promote regeneration in the transected nude rat spinal cord.

Advances in the purification and expansion of Schwann cells (SCs) from adult human peripheral nerve, together with biomaterials development, have made the construction of unique grafts with defined properties possible. We have utilized PAN/PVC guidance channels to form solid human SC grafts which can be transplanted either with or without the channel. We studied the ability of grafts placed with and without channels to support regeneration and to influence functional recovery; characteristics of the graft and host/graft interface were also compared.

The astroglial response to Wallerian degeneration after spinal cord injury in humans.

We describe the changes exhibited by astrocytes in areas of Wallerian degeneration after spinal cord injury in humans using glial fibrillary acidic protein immunohistochemistry correlated to standard histology at time points ranging from 8 days to 23 years after injury. Astrocytes were slow to react; a slight increase in immunoreactivity was observed at 4 months. Over time they began to lose immunoreactivity in both the somata and the processes as the debris from the degenerative process was cleared.

Influence of IN-1 antibody and acidic FGF-fibrin glue on the response of injured corticospinal tract axons to human Schwann cell grafts.

Two strategies have been shown by others to improve CST regeneration following thoracic spinal cord injury: 1) the administration of a monoclonal antibody, IN-1, raised against a myelin-associated, neurite growth inhibitory protein, and 2) the delivery of acidic fibroblast growth factor (aFGF) in fibrin glue in association with peripheral nerve grafts. Because autologous transplantation of human Schwann cells (SCs) is a potential strategy for CNS repair, we evaluated the ability of these two molecular agents to induce CST regeneration into human SC grafts placed to span a midthoracic spinal cord transection in the adult nude rat, a xenograft tolerant strain. IN-1 or control (HRP) antibodies were delivered to the injury/graft region by encapsulated hybridoma cells ("IN-1 ravioli") or daily infusion of hybridoma culture supernatant; aFGF-fibrin glue was placed in the same region in other animals.

High-resolution diffusion-weighted MR of fresh and fixed cat spinal cords: evaluation of diffusion coefficients and anisotropy.

Purpose: To use high-resolution diffusion-weighted and calculated apparent diffusion coefficient (ADC) MR imaging to determine whether fixation and storage influence diffusion anisotropy in white matter tracts of cat spinal cord specimens.

Methods: Four cat cord specimens were imaged using a diffusion-weighted spin-echo sequence. Diffusion encoding was applied in the section-select axis (parallel to white matter tracts) and in the read axis (perpendicular to white matter tracts).