Electrical Stimulation for Low-Energy Termination of Cardiac Arrhythmias: a Review.

Cardiac arrhythmias are a leading cause of morbidity and mortality in the developed world, estimated to be responsible for hundreds of thousands of deaths annually. Our understanding of the electrophysiological mechanisms of such arrhythmias has grown since they were formally characterized in the late nineteenth century, and this has led to the development of numerous devices and therapies that have markedly improved outcomes for patients affected by such conditions. Despite these advancements, the application of a single large shock remains the clinical standard for treating deadly tachyarrhythmias. Such defibrillating shocks are undoubtedly effective in terminating such arrhythmias; however, they are applied without forewarning, contributing to the patient's stress and anxiety; they can be intensely painful; and they can have adverse psychological and physiological effects on patients. In recent years, there has been interest in developing defibrillation protocols that can terminate arrhythmias without crossing the human pain threshold for energy delivery, generally estimated to be between 0.1 and 1 J. In this article, we review existing literature on the development of such low-energy defibrillation methods and their underlying mechanisms, in an attempt to broadly describe the current landscape of these technologies.

An initial ex vivo evaluation of temperature profile and thermal injury formation on the epiesophageal surface during radiofrequency ablation.

INTRODUCTION: Few studies have examined heat transfer and thermal injury on the epiesophageal surface during radiofrequency application, or compared the risk of esophageal thermal injury between standard and high-power, short-duration (HPSD) ablation. We studied the thermodynamics of HPSD and standard ablation at different tissue interfaces between the left atrium and esophagus, focusing on epiesophageal temperature changes and thermal injury. METHODS AND RESULTS: Fresh porcine heart and esophageal sections were secured to a custom holder and submerged in a temperature-controlled, circulating water bath. During ablation, thermistors recorded temperatures at the catheter tip-atrial interface, epiesophageal-atrial interface, and esophageal lumen. Samples were ablated in triplicate with the following parameters: contact force (15/25g), power (10/20/30 W standard; 40/45/50 W HPSD), and duration (10/20/30 s standard; 5/10/15 s HPSD). Epiesophageal and endoluminal temperature rises were greater in HPSD than in standard ablation (epiesophageal: 5.9 ± 5.6 vs. 2.2 ± 2.0°C, p < .01; endoluminal: 0.7 ± 0.5 vs. 0.4 ± 0.2°C, p < .01). Six of 30 HPSD ablations and 1 of 26 standard ablations caused esophageal injury. The delay between the peak epiesophageal and endoluminal temperatures was greater in HPSD than in standard ablation (24.2 ± 22.1 vs. 13.0 ± 11.0 s, p = .023). Likewise, the peak epiesophageal surface temperature differed more from the concurrent endoluminal temperature in HPSD ablation (5.1 ± 5.3 vs. 1.7 ± 2.0°C, p < .01). CONCLUSION: Endoluminal temperature underestimates epiesophageal surface temperature substantially during HPSD ablation. Visible epiesophageal injury was associated with a 2.2 ± 2.1°C rise in endoluminal temperature, corresponding to a 10.2 ± 6.5°C rise in epiesophageal temperature.

Trauma patients have reduced ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model of vessel injury.

Trauma is the leading cause of death in individuals up to 45 years of age. Alterations in platelet function are a critical component of trauma-induced coagulopathy (TIC), yet these changes and the potential resulting dysfunction is incompletely understood. The lack of clinical assays available to explore platelet function in this patient population has hindered detailed understanding of the role of platelets in TIC. The objective of this study was to assess trauma patient ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model. We hypothesized that trauma patients would have flow-regime dependent alterations in platelet function. Blood was collected from trauma patients with level I activations (N = 34) within 60 min of hospital arrival, as well as healthy volunteer controls (N = 10). Samples were perfused through a microfluidic model of injury at venous and arterial shear rates, and a subset of experiments were performed after incubation with fluorescent anti-CD41 to quantify platelets. Complete blood counts were performed as well as plasma-based assays to quantify coagulation times, fibrinogen, and von Willebrand factor (VWF). Exploratory correlation analyses were employed to identify relationships with microfluidic hemostatic parameters. Trauma patients had increased microfluidic bleeding times compared to healthy controls. While trauma patient samples were able to deposit a substantial amount of clot in the model injury site, the platelet contribution to microfluidic hemostasis was attenuated. Trauma patients had largely normal hematology and plasma-based coagulation times, yet had elevated D-Dimer and VWF. Venous microfluidic bleeding time negatively correlated with VWF, D-Dimer, and mean platelet volume (MPV), while arterial microfluidic bleeding time positively correlated with oxygenation. Arterial clot growth rate negatively correlated with red cell count, and positively with mean corpuscular volume (MCV). We observed changes in clot composition in trauma patient samples reflected by significantly diminished platelet contribution, which resulted in reduced hemostatic function in a microfluidic model of vessel injury. We observed a reduction in platelet clot contribution under both venous and arterial flow ex vivo in trauma patient samples. While our population was heterogenous and had relatively mild injury severity, microfluidic hemostatic parameters correlated with different patient-specific data depending on the flow setting, indicating potentially differential mechanistic pathways contributing to platelet hemostatic capacity in the context of TIC. These data were generated with the goal of identifying key features of platelet dysfunction in bleeding trauma patients under conditions of flow and to determine if these features correlate with clinically available metrics, thus providing preliminary surrogate markers of physiological platelet dysfunction to be further studied across larger cohorts. Future studies will continue to explore those relationships and further define mechanisms of TIC and their relationship with patient outcomes.

High porosity PEG-based hydrogel foams with self-tuning moisture balance as chronic wound dressings.

A major challenge in chronic wound treatment is maintaining an appropriate wound moisture balance throughout the healing process. Wound dehydration hinders wound healing due to impeded molecule transport and cell migration with associated tissue necrosis. In contrast, wounds that produce excess fluid contain high levels of reactive oxygen species and matrix metalloproteases that impede cell recruitment, extracellular matrix reconstruction, and angiogenesis. Dressings are currently selected based on the relative amount of wound exudate with no universal dressing available that can maintain appropriate wound moisture balance to enhance healing. This work aimed to develop a high porosity poly(ethylene glycol) diacrylate hydrogel foam that can both rapidly remove exudate and provide self-tuning moisture control to prevent wound dehydration. A custom foaming device was used to vary hydrogel foam porosity from 25% to 75% by adjusting the initial air-to-solution volume ratio. Hydrogel foams demonstrated substantial improvements in water uptake volume and rate as compared to bulk hydrogels while maintaining similar hydration benefits with slow dehydration rates. The hydrogel foam with the highest porosity (~75%) demonstrated the greatest water uptake and rate, which outperformed commercial dressing products, Curafoam® and Silvercel®, in water absorption, moisture retention, and exudate management. Investigation of the water vapor transmission rates of each dressing at varied hydration levels was characterized and demonstrated the dynamic moisture-controlling capability of the hydrogel foam dressing. Overall, the self-tuning moisture control of this hydrogel foam dressing holds great promise to improve healing outcomes for both dry and exudative chronic wounds.

Review of Integrin-Targeting Biomaterials in Tissue Engineering.

The ability to direct cell behavior has been central to the success of numerous therapeutics to regenerate tissue or facilitate device integration. Biomaterial scientists are challenged to understand and modulate the interactions of biomaterials with biological systems in order to achieve effective tissue repair. One key area of research investigates the use of extracellular matrix-derived ligands to target specific integrin interactions and induce cellular responses, such as increased cell migration, proliferation, and differentiation of mesenchymal stem cells. These integrin-targeting proteins and peptides have been implemented in a variety of different polymeric scaffolds and devices to enhance tissue regeneration and integration. This review first presents an overview of integrin-mediated cellular processes that have been identified in angiogenesis, wound healing, and bone regeneration. Then, research utilizing biomaterials are highlighted with integrin-targeting motifs as a means to direct these cellular processes to enhance tissue regeneration. In addition to providing improved materials for tissue repair and device integration, these innovative biomaterials provide new tools to probe the complex processes of tissue remodeling in order to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.