Precision sampling of discrete sites identified during in-vivo functional testing in the mammalian heart.

Ventricular arrhythmias after myocardial infarction (MI) originate from discrete areas within the MI border zone (BZ), identified during functional electrophysiology tests. Accurate sampling of arrhythmogenic sites for ex-vivo study remains challenging, yet is critical to identify their tissue, cellular and molecular signature. In this study, we developed, validated, and applied a targeted sampling methodology based on individualized 3D prints of the human-sized pig heart.

Slower Calcium Handling Balances Faster Cross-Bridge Cycling in Human HCM.

Background: The pathogenesis of -associated hypertrophic cardiomyopathy (HCM) is still unresolved. In our HCM patient cohort, a large and well-characterized population carrying the :c772G>A variant (p.Glu258Lys, E258K) provides the unique opportunity to study the basic mechanisms of -HCM with a comprehensive translational approach.

Quantification of Myocyte Disarray in Human Cardiac Tissue.

Proper three-dimensional (3D)-cardiomyocyte orientation is important for an effective tension production in cardiac muscle. Cardiac diseases can cause severe remodeling processes in the heart, such as cellular misalignment, that can affect both the electrical and mechanical functions of the organ. To date, a proven methodology to map and quantify myocytes disarray in massive samples is missing.

Mesoscopic Optical Imaging of Whole Mouse Heart.

Both genetic and non-genetic cardiac diseases can cause severe remodeling processes in the heart. Structural remodeling, such as collagen deposition (fibrosis) and cellular misalignment, can affect electrical conduction, introduce electromechanical dysfunctions and, eventually, lead to arrhythmia. Current predictive models of these functional alterations are based on non-integrated and low-resolution structural information.

Optical clearing in cardiac imaging: A comparative study.

The optical clearing of the cardiac tissue has always been a challenging goal to obtain successful three-dimensional reconstructions of entire hearts. Typically, the developed protocols are targeted at the clearing of the brain; cardiac tissue requires proper arrangements to the original protocols, which are usually tough and time-consuming to figure out. Here, we present the application of three different clearing methodologies on mouse hearts: uDISCO, CLARITY, and SHIELD.

Autofluorescence enhancement for label-free imaging of myelinated fibers in mammalian brains.

Analyzing the structure of neuronal fibers with single axon resolution in large volumes is a challenge in connectomics. Different technologies try to address this goal; however, they are limited either by the ineffective labeling of the fibers or in the achievable resolution. The possibility of discriminating between different adjacent myelinated axons gives the opportunity of providing more information about the fiber composition and architecture within a specific area.

3D imaging and morphometry of the heart capillary system in spontaneously hypertensive rats and normotensive controls.

Systemic arterial hypertension is a highly prevalent chronic disease associated with hypertensive cardiomyopathy. One important feature of this condition is remodelling of intramural small coronary arteries and arterioles. Here, we investigated the implications of this remodelling in the downstream vascular organization, in particular at the capillary level.

A Software Architecture to Mimic a Ventricular Tachycardia in Intact Murine Hearts by Means of an All-Optical Platform.

Optogenetics is an emerging method that uses light to manipulate electrical activity in excitable cells exploiting the interaction between light and light-sensitive depolarizing ion channels, such as channelrhodopsin-2 (ChR2). Initially used in the neuroscience, it has been adopted in cardiac research where the expression of ChR2 in cardiac preparations allows optical pacing, resynchronization and defibrillation. Recently, optogenetics has been leveraged to manipulate cardiac electrical activity in the intact heart in real-time.