Changes in attachment and metabolic activity of rat neonatal cardiomyocytes and nonmyocytes caused by Macrovipera lebetina obtusa venom.

The Caucasian viper Macrovipera lebetina obtusa (MLO) is one of the most prevalent and venomous snakes in the Caucasus and the surrounding regions, yet the effects of MLO venom on cardiac function remain largely unknown. We examined the influence of MLO venom (crude and with inhibited metalloproteinases and phospholipase A) on attachment and metabolic activity of rat neonatal cardiomyocytes (CM) and nonmyocytes (nCM), assessed at 1 and 24 h. After exposing both CM and nCM to varying concentrations of MLO venom, we observed immediate cytotoxic effects at a concentration of 100 μg/ml, causing detachment from the culture substrate.

The essential role of arterial pulse in venous return.

The close proximity of arteries and veins is a well-known anatomical finding documented in the extremities of all vertebrates. However, the physiological consequences of this arrangement are rarely given proper consideration nor are they covered in the textbook list of mechanisms that aid blood flow. We hypothesized that arterial pressure pulsations can significantly increase blood flow in the adjacent valve-containing vein segments.

Building Valveless Impedance Pumps From Biological Components: Progress and Challenges.

Valveless pumping based on Liebau mechanism entails asymmetrical positioning of the compression site relative to the attachment sites of the pump's elastic segment to the rest of the circuit. Liebau pumping is believed to play a key role during heart development and be involved in several other physiological processes. Until now studies of Liebau pump have been limited to numerical analyses, modeling, experiments using non-biological elements, and a few indirect measurements.

Output of a valveless Liebau pump with biologically relevant vessel properties and compression frequencies.

Liebau pump is a tubular, non-peristaltic, pulsatile pump capable of creating unidirectional flow in the absence of valves. It requires asymmetrical positioning of the pincher relative to the attachment sites of its elastic segment to the rest of the circuit. Biological feasibility of such valveless pumps remains a hotly debated topic.

Autofluorescence properties of balloon polymers used in medical applications.

Significance: For use in medical balloons and related clinical applications, polymers are usually designed for transparency under illumination with white-light sources. However, when illuminated with ultraviolet (UV) or blue light, most of these materials autofluoresce in the visible range, which can be a concern for modalities that rely on tissue autofluorescence for diagnostic or therapeutic purposes.

Aim: A search for published information on spectral properties of polymers that can be used for medical balloon manufacturing revealed a scarcity of published information on this subject.

Optical mapping of human embryonic stem cell-derived cardiomyocyte graft electrical activity in injured hearts.

Background: Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) show tremendous promise for cardiac regeneration, but the successful development of hESC-CM-based therapies requires improved tools to investigate their electrical behavior in recipient hearts. While optical voltage mapping is a powerful technique for studying myocardial electrical activity ex vivo, we have previously shown that intra-cardiac hESC-CM grafts are not labeled by conventional voltage-sensitive fluorescent dyes. We hypothesized that the water-soluble voltage-sensitive dye di-2-ANEPEQ would label engrafted hESC-CMs and thereby facilitate characterization of graft electrical function and integration.

Key factors behind autofluorescence changes caused by ablation of cardiac tissue.

Radiofrequency ablation is a commonly used clinical procedure that destroys arrhythmogenic sources in patients suffering from atrial fibrillation and other types of cardiac arrhythmias. To improve the success of this procedure, new approaches for real-time visualization of ablation sites are being developed. One of these promising methods is hyperspectral imaging, an approach that detects lesions based on changes in the endogenous tissue autofluorescence profile.

A Percutaneous Catheter for In Vivo Hyperspectral Imaging of Cardiac Tissue: Challenges, Solutions and Future Directions.

Purpose: Multiple studies have shown that spectral analysis of tissue autofluorescence can be used as a live indicator for various pathophysiological states of cardiac tissue, including ischemia, ablation-induced damage, or scar formation. Yet today there are no percutaneous devices that can detect autofluorescence signals from inside a beating heart. Our aim was to develop a prototype catheter to demonstrate the feasibility of doing so.

Agarose Slurry as a Support Medium for Bioprinting and Culturing Freestanding Cell-Laden Hydrogel Constructs.

We present a modified method of embedded bioprinting, which allows maintaining freestanding three-dimensional (3D) printed structures in cell culture conditions for extended periods of time. This method, termed CLASS (constructs laid in agarose slurry suspension), was tested using cell-laden alginate and gelatin methacrylate (GelMa)-based bioinks. A direct comparison of 3D printed constructs, supported by gelatin and agarose hydrogel slurries, revealed several advantages, including slurry stability across different print temperatures and blending times, increased slurry homogeneity, and the ability of CLASS to support freestanding constructs for an extended time in cell culture.

Use of GelMA for 3D printing of cardiac myocytes and fibroblasts.

Aim: To 3D print heart tissue, one must understand how the main two types of cardiac cells are affected by the printing process.

Materials & Methods: Effects of gelatin methacryloyl (GelMA) concentration, extruder pressure and duration of UV exposure on survival of cardiac myocytes and fibroblasts were examined using lactate dehydrogenase and LIVE/DEAD assays, bioluminescence imaging and morphological assessment.

Results & Conclusion: Cell survival within 3D printed cardiomyocyte-laden GelMA constructs was more sensitive to extruder pressure and GelMA concentrations than within 3D fibroblast-laden GelMA constructs.

Application of unsupervised learning to hyperspectral imaging of cardiac ablation lesions.

Atrial fibrillation is the most common cardiac arrhythmia. It is being effectively treated using the radiofrequency ablation (RFA) procedure, which destroys culprit tissue and creates scars that prevent the spread of abnormal electrical activity. Long-term success of RFA could be improved further if ablation lesions can be directly visualized during the surgery.

Optimization of wavelength selection for multispectral image acquisition: a case study of atrial ablation lesions.

In vivo autofluorescence hyperspectral imaging of moving objects can be challenging due to motion artifacts and to the limited amount of acquired photons. To address both limitations, we selectively reduced the number of spectral bands while maintaining accurate target identification. Several downsampling approaches were applied to data obtained from the atrial tissue of adult pigs with sites of radiofrequency ablation lesions.

Hyperspectral imaging for label-free in vivo identification of myocardial scars and sites of radiofrequency ablation lesions.

Background: Treatment of cardiac arrhythmias often involves ablating viable muscle tissue within or near islands of scarred myocardium. Yet, today there are limited means by which the boundaries of such scars can be visualized during surgery and distinguished from the sites of acute injury caused by radiofrequency (RF) ablation.

Objective: We sought to explore a hyperspectral imaging (HSI) methodology to delineate and distinguish scar tissue from tissue injury caused by RF ablation.

Anatomical and Optical Properties of Atrial Tissue: Search for a Suitable Animal Model.

The purpose of this study was to evaluate structural and optical properties of atrial tissue from common animal models and to compare it with human atria. We aimed to do this in a format that will be useful for development of better ablation tools and/or new means for visualizing atrial lesions. Human atrial tissue from clinically relevant age group was compared and contrasted with atrial tissue of large animal models commonly available for research purposes.

Seeing the Invisible: Revealing Atrial Ablation Lesions Using Hyperspectral Imaging Approach.

Background: Currently, there are limited means for high-resolution monitoring of tissue injury during radiofrequency ablation procedures.

Objective: To develop the next generation of visualization catheters that can reveal irreversible atrial muscle damage caused by ablation and identify viability gaps between the lesions.

Methods: Radiofrequency lesions were placed on the endocardial surfaces of excised human and bovine atria and left ventricles of blood perfused rat hearts.

Autofluorescence hyperspectral imaging of radiofrequency ablation lesions in porcine cardiac tissue.

Radiofrequency ablation (RFA) is a widely used treatment for atrial fibrillation, the most common cardiac arrhythmia. Here, we explore autofluorescence hyperspectral imaging (aHSI) as a method to visualize RFA lesions and interlesional gaps in the highly collagenous left atrium. RFA lesions made on the endocardial surface of freshly excised porcine left atrial tissue were illuminated by UV light (365 nm), and hyperspectral datacubes were acquired over the visible range (420-720 nm).

HLA Class I Depleted hESC as a Source of Hypoimmunogenic Cells for Tissue Engineering Applications.

Background: Rapidly improving protocols for the derivation of autologous cells from stem cell sources is a welcome development. However, there are many circumstances when off-the-shelf universally immunocompatible cells may be needed. Embryonic stem cells (ESCs) provide a unique opportunity to modify the original source of differentiated cells to minimize their rejection by nonautologous hosts.

Physiological response of cardiac tissue to bisphenol A: alterations in ventricular pressure and contractility.

Biomonitoring studies have indicated that humans are routinely exposed to bisphenol A (BPA), a chemical that is commonly used in the production of polycarbonate plastics and epoxy resins. Epidemiological studies have shown that BPA exposure in humans is associated with cardiovascular disease; however, the direct effects of BPA on cardiac physiology are largely unknown. Previously, we have shown that BPA exposure slows atrioventricular electrical conduction, decreases epicardial conduction velocity, and prolongs action potential duration in excised rat hearts.

Exposure to phthalates affects calcium handling and intercellular connectivity of human stem cell-derived cardiomyocytes.

Background: The pervasive nature of plastics has raised concerns about the impact of continuous exposure to plastic additives on human health. Of particular concern is the use of phthalates in the production of flexible polyvinyl chloride (PVC) products. Di-2-ethylhexyl-phthalate (DEHP) is a commonly used phthalate ester plasticizer that imparts flexibility and elasticity to PVC products.

Downregulation of beta-microglobulin to diminish T-lymphocyte lysis of non-syngeneic cell sources of engineered heart tissue constructs.

The presence of non-autologous major histocompatibility complex class I (MHC-I) molecules on the surface of the grafted cells is one of the main reasons for their rejection in non-syngeneic hosts. We present a straightforward strategy to decrease the presence of MHC-I by shRNA inhibition of beta-2-microglobulin (B2M), a conservative light chain of MHC-I, on the surface of two main cell types that are used to engineer heart tissue constructs. Engineered heart tissue constructs can be generated by combining mouse WT19 fibroblasts and mouse embryonic stem cell-derived cardiac myocytes (mESC-CM).

Visualization of epicardial cryoablation lesions using endogenous tissue fluorescence.

Background: Percutaneous cryoballoon ablation is a commonly used procedure to treat atrial fibrillation. One of the major limitations of the procedure is the inability to directly visualize tissue damage and functional gaps between the lesions. We seek to develop an approach that will enable real-time visualization of tissue necrosis during cryo- or radiofrequency ablation procedures.

Thinking Outside the Heart: Use of Engineered Cardiac Tissue for the Treatment of Chronic Deep Venous Insufficiency.

This article considers the use of autologous stem cell-derived cardiomyocytes as a novel means to aid venous return. The approach consists of creating external cuffs of engineered heart tissue around vein segments with incompetent or poorly competent valves. The engineered heart tissue cuff prevents distention of the impaired vein segments and aids unidirectional flow by its rhythmic contractions.

Bisphenol A exposure and cardiac electrical conduction in excised rat hearts.

Background: Bisphenol A (BPA) is used to produce polycarbonate plastics and epoxy resins that are widely used in everyday products, such as food and beverage containers, toys, and medical devices. Human biomonitoring studies have suggested that a large proportion of the population may be exposed to BPA. Recent epidemiological studies have reported correlations between increased urinary BPA concentrations and cardiovascular disease, yet the direct effects of BPA on the heart are unknown.

Properties of blebbistatin for cardiac optical mapping and other imaging applications.

Blebbistatin is a recently discovered myosin II inhibitor. It is rapidly becoming a compound of choice to reduce motion artifacts during cardiac optical mapping, as well as to study cell motility and cell invasion. Although blebbistatin has a number of advantages over other electromechanical uncouplers, many of its properties have yet to be addressed.