Biophysics and electrophysiology of pulsed field ablation in normal and infarcted porcine cardiac ventricular tissue.

Pulsed Field Ablation (PFA) is a new ablation method being rapidly adopted for treatment of atrial fibrillation, which shows advantages in safety and efficiency over radiofrequency and cryo-ablation. In this study, we used an in vivo swine model (10 healthy and 5 with chronic myocardial infarct) for ventricular PFA, collecting intracardiac electrograms, electro-anatomical maps, native T1-weighted and late gadolinium enhancement MRI, gross pathology, and histology. We used 1000-1500 V pulses, with 1-16 pulse trains to vary PFA dose.

The importance of electrode-tissue proximity in creating pulsed field ablation lesions: insights from a sub-acute preclinical model.

Background: We sought to evaluate the anatomic and functional lesion development over time at different atrial sites immediately following delivery of pulsed field ablation (PFA).

Methods: Using a porcine model, PFA ablations were performed in the superior vena cava (SVC), right atrial lateral wall (RA), left atrial appendage (LAA), and right superior pulmonary vein (RSPV) using four different PFA profiles. Mapping was done sequentially in 5-20-min increments up to 280-min post lesion delivery for low voltage area (LVA) assessment and conduction velocity.

Effects of envelopes on cardiac implantable electronic device pocket healing: A head-to-head preclinical evaluation.

Background: The healing response to cardiac implantable electronic device (CIED) implantation results in inflammation that can lead to fibrous pocket formation, which may disrupt pocket healing or complicate future interventions.

Objective: The purpose of this study was to assess CIED pocket healing with use of the second-generation TYRX absorbable antibacterial envelope (T2), the next-generation (NG) TYRX absorbable antibacterial envelope under development, and the CanGaroo® extracellular matrix envelope (ECM) compared to no envelope.

Methods: A total of 110 CIEDs were implanted in an ovine model, either with (T2, NG, or ECM) or without envelopes.

Swine models in translational research and medicine.

Swine are increasingly studied as animal models of human disease. The anatomy, size, longevity, physiology, immune system, and metabolism of swine are more like humans than traditional rodent models. In addition, the size of swine is preferred for surgical placement and testing of medical devices destined for humans.

Preclinical evaluation of a third-generation absorbable antibacterial envelope.

Background: The TYRX (Medtronic) absorbable antibacterial envelope has been shown to stabilize implantable cardiac devices and reduce infection. A third-generation envelope was developed to reduce surface roughness with a redesigned multifilament mesh and enhanced form factor but identical polymer coating and antibiotic concentrations as the currently available second-generation envelope.

Objective: The purpose of this study was to compare drug elution, bacterial challenge efficacy, stabilization, and absorption of second- vs third-generation envelopes.

Characterization of Phrenic Nerve Response to Pulsed Field Ablation.

Background: Phrenic nerve palsy is a well-known complication of cardiac ablation, resulting from the application of direct thermal energy. Emerging pulsed field ablation (PFA) may reduce the risk of phrenic nerve injury but has not been well characterized.

Methods: Accelerometers and continuous pacing were used during PFA deliveries in a porcine model.

Safety and chronic lesion characterization of pulsed field ablation in a Porcine model.

Background: Pulsed field ablation (PFA) has been identified as an alternative to thermal-based ablation systems for treatment of atrial fibrillation patients. The objective of this Good Laboratory Practice (GLP) study was to characterize the chronic effects and safety of overlapping lesions created by a PFA system at intracardiac locations in a porcine model.

Methods: A circular catheter with nine gold electrodes was used for overlapping low- or high-dose PFA deliveries in the superior vena cava (SVC), right atrial appendage (RAA), and right superior pulmonary vein (RSPV) in six pigs.

Reduction in Pulmonary Vein Stenosis and Collateral Damage With Pulsed Field Ablation Compared With Radiofrequency Ablation in a Canine Model.

Background: Pulmonary vein (PV) stenosis is a highly morbid condition that can result after catheter ablation for PV isolation. We hypothesized that pulsed field ablation (PFA) would reduce PV stenosis risk and collateral injury compared with irrigated radiofrequency ablation (IRF).

Methods: IRF and PFA deliveries were randomized in 8 dogs with 2 superior PVs ablated using one technology and 2 inferior PVs ablated using the other technology.

What Is "Preclinical Device Pathology": An Introduction of the Unfamiliar.

Medical device pathologists are involved in the preclinical evaluation of medical devices that will be temporarily inserted or permanently and often irreversibly implanted in the human body. The medical device industry is technology based, allowing for rapid device iterations; innovations occur at an accelerated rate compared to the innovations in the pharmaceutical industry. The device pathologist provides the pathology results and is, by training and experience, in an ideal position to help the medical engineer and innovator tackle biomedical problems and to comment on the possible and actual outcomes of preclinical studies.

Intracardiac pulsed field ablation: Proof of feasibility in a chronic porcine model.

Background: Radiofrequency (RF) has become an accepted energy source for myocardial ablation but may result in discontinuous lesions and nontargeted tissue injury. We examined the feasibility and safety of lesion formation using high-amplitude, bipolar pulsed electric fields delivered from a multielectrode array catheter.

Objective: The purpose of this study was to compare duty-cycled radiofrequency ablation (RFA) to pulsed field ablation (PFA) in terms of acute electrical effects, 2-week lesion formation, and injury to nontargeted tissues.

Dosing of the second-generation cryoballoon using acute time-to-pulmonary vein isolation as an indicator of durable ablation in a canine model.

Background: Rigid time-based dosing protocol(s) currently used in the clinic for cryoballoon ablation of atrial fibrillation may be inadequate to guide the circumferential and transmural cryothermal energy transfer across the pulmonary vein (PV) and may result in injury to collateral tissues or electrical gaps between the PV and left atrium (LA).

Objective: A physiologic endpoint (e.g.

Comparison of a Saline-coupled Bipolar Sealer Versus Traditional Electrosurgery in a Porcine Model of Chronic Wound Healing.

Objective: This study examines the healing dynamics of in vivo porcine muscle tissue wounds hemostatically treated with a saline-coupled bipolar tissue sealer (SCBS) compared with traditional electrosurgical (ES) coagulation.

Materials And Methods: Six cutaneous incisions were created on the dorsum of 28 adult male Yorkshire swine. The underlying muscle tissue was incised with a cold scalpel then treated with either SCBS (at 170 W) or traditional ES (at Coag 45 W).

Two-year extractability of novel left ventricular, active fixation leads in the sheep model.

Background: A cardiac lead with a side helix for active fixation to the coronary vein wall (Attain Stability , Model 20066, Medtronic, Minneapolis, MN, USA) recently received CE Mark. The lead is designed to improve left ventricular (LV) placement and reduce dislodgement rates. The extractability of this active fixation LV lead has not been studied extensively.

Predictability of lesion durability for AF ablation using phased radiofrequency: Power, temperature, and duration impact creation of transmural lesions.

Background: Long-term clinical outcomes for atrial fibrillation ablation depend on the creation of durable transmural lesions during pulmonary vein isolation and on substrate modification. Focal conventional radiofrequency (RF) ablation studies have demonstrated that tissue temperature and power are important factors for lesion formation. However, the impact and predictability of temperature and power on contiguous, transmural lesion formation with a phased RF system has not been described.

The Biophysics of Passive Convective Cooling During Catheter Ablation with Gold versus Platinum Electrodes and Multielectrode Phased Radiofrequency Energy Delivery.

Introduction: During radiofrequency (RF) catheter ablation, convective cooling of the ablated tissue by circulating blood allows higher power delivery and deeper penetration of volume heating without excess surface heating. The study aim was to characterize ablation lesions using electrode materials with differing thermal conductivities and magnitudes of passive convective cooling utilizing duty-cycled RF energy.

Methods And Results: RF ablations using a linear array of 4 3-mm platinum electrodes (n = 228) were compared to an array with gold electrodes (n = 244).

Effect of Steroid Elution on Electrical Performance and Tissue Responses in Quadripolar Left Ventricular Cardiac Vein Leads.

Introduction: The use of steroid elution (SE) electrode in a cardiac pacing lead is known to suppress myocardial inflammation to lower pacing thresholds (PTs). SE has been widely utilized on the distal electrode of left ventricular cardiac vein (LVCV) leads used in cardiac resynchronization therapy (CRT). However, no paired comparison in effect of SE has been studied in proximal electrodes of quadripolar LVCV leads.

Microembolism and catheter ablation I: a comparison of irrigated radiofrequency and multielectrode-phased radiofrequency catheter ablation of pulmonary vein ostia.

Background: Cerebral diffusion-weighted MRI lesions have been observed after catheter ablation of atrial fibrillation. We hypothesized that conditions predisposing to microembolization could be identified using a porcine model of pulmonary vein ablation and an extracorporeal circulation loop.

Methods And Results: Ablations of the pulmonary veins were performed in 18 swine with echo monitoring.

Microembolism and catheter ablation II: effects of cerebral microemboli injection in a canine model.

Background: Asymptomatic cerebral lesions have been observed on diffusion weighted MRI (DWI) scans shortly after catheter ablation of atrial fibrillation, but the pathogenesis of these lesions is incompletely understood.

Methods And Results: Twelve dogs underwent selective catheterization of the internal carotid or vertebral arteries. Either a microbubbled mixture of air (1.

Opsonizing properties of rat ficolin-A in the defence against Cryptococcus neoformans.

Cryptococcus neoformans is a pathogenic fungus causing life threatening infections in humans. The present in vitro study aimed to investigate the opsonizing properties of a well characterized serum ficolin (rat ficolin-A), a member of carbohydrate-recognition molecules of the innate immune system, in the defence against this fungal pathogen. Using flow cytometric analysis we have been able to demonstrate that ficolin-A readily binds to two different acapsular C.

Targeted overexpression of an activated N-ras gene results in B-cell and plasma cell lymphoproliferation and cooperates with c-myc to induce fatal B-cell neoplasia.

Multiple myeloma is an incurable malignant expansion of plasma cells in the bone marrow. Although there is no pathognomonic genetic lesion among multiple myeloma patients, activation of the ras gene has been identified as a common mutation. We have previously described the use of the 3' κ immunoglobulin light chain enhancer (3'KE) to target transgenic expression in murine B and plasma cells, resulting in bcl-X(L) and c-myc-driven murine models of multiple myeloma.

Transmural atrial fibrosis after epicardial and endocardial argon-powered CryoMaze ablation.

Background: The CryoMaze procedure is usually limited to endocardial ablation under cardio-pulmonary bypass. Epicardial ablation is considered inferior as endocardial islets of atrial tissue could theoretically remain viable, protected from cryoinjury by epicardial fat and endocardial circulating warm blood. Novel argon-powered cryoprobes with lower ablation temperatures have recently become available.

Cardiac ablation via electroporation.

Thermal-based ablation for the treatment of arrhythmias is known to cause issues (e.g. heat loss due to blood perfusion, mechanical damage of the tissue from excessive heat, etc.

Quadrupole magnetic sorting of porcine islets of Langerhans.

Islet transplantation is emerging as a treatment option for selected patients with type 1 diabetes. Inconsistent isolation, purification, and recovery of large numbers of high-quality islets remain substantial impediments to progress in the field. Removing islets as soon as they are liberated from the pancreas during digestion and circumventing the need for density gradient purification is likely to result in substantially increased viable islet yields by minimizing exposure to proteolytic enzymes, reactive oxygen intermediates, and mechanical stress associated with centrifugation.

A murine Mll-AF4 knock-in model results in lymphoid and myeloid deregulation and hematologic malignancy.

The 2 most frequent human MLL hematopoietic malignancies involve either AF4 or AF9 as fusion partners; each has distinct biology but the role of the fusion partner is not clear. We produced Mll-AF4 knock-in (KI) mice by homologous recombination in embryonic stem cells and compared them with Mll-AF9 KI mice. Young Mll-AF4 mice had lymphoid and myeloid deregulation manifest by increased lymphoid and myeloid cells in hematopoietic organs.

Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates.

Cell-based diabetes therapy requires an abundant cell source. Here, we report reversal of diabetes for more than 100 d in cynomolgus macaques after intraportal transplantation of cultured islets from genetically unmodified pigs without Gal-specific antibody manipulation. Immunotherapy with CD25-specific and CD154-specific monoclonal antibodies, FTY720 (or tacrolimus), everolimus and leflunomide suppressed indirect activation of T cells, elicitation of non-Gal pig-specific IgG antibody, intragraft expression of proinflammatory cytokines and invasion of infiltrating mononuclear cells into islets.