Preparation of Human Atrial Trabeculae for Ex Vivo Analysis of Human Myocardial Function.

Human myocardial function can be investigated in the laboratory using human atrial trabeculae. These multicellular preparations provide a translatable model for assessing the ex vivo contractility, electrophysiology, and ionic and metabolic underpinnings of human cardiac muscle. Here, we detail the materials and methods required to determine the baseline function of a human atrial trabecula, from dissection to stimulation.

Association of epicardial adipose tissue volume with heart weight in post-mortem cases.

Epicardial adipose tissue (EAT) deposition has been long associated with heart weight. However, recent research has failed to replicate this association. We aimed to determine the association of EAT volume with heart weight in post-mortem cases and identify potential confounding variables.

Cardiac effects of myoregulin in ischemia-reperfusion.

Myoregulin is a recently discovered micropeptide that controls calcium levels by inhibiting the intracellular calcium pump sarco-endoplasmic reticulum Ca-ATPase (SERCA). Keeping calcium levels balanced in the heart is essential for normal heart functioning, thus myoregulin has the potential to be a crucial regulator of cardiac muscle performance by reducing the rate of intracellular Ca uptake. We provide the first report of myoregulin mRNA expression in human heart tissue, absence of expression in human plasma, and the effects of myoregulin on cardiac hemodynamics in an ex vivo Langendorff isolated rat heart model of ischemia/reperfusion.

An arrhythmogenic metabolite in atrial fibrillation.

Background: Long-chain acyl-carnitines (ACs) are potential arrhythmogenic metabolites. Their role in atrial fibrillation (AF) remains incompletely understood. Using a systems medicine approach, we assessed the contribution of C18:1AC to AF by analysing its in vitro effects on cardiac electrophysiology and metabolism, and translated our findings into the human setting.

Depressed HCN4 function in the type 2 diabetic sinoatrial node.

Diabetic patients often have impaired heart rate (HR) control. HR is regulated both intrinsically within the sinoatrial node (SAN) and via neuronal input. Previously, we found lower ex vivo HR in type 2 diabetic rat hearts, suggesting impaired HR generation within the SAN.

Sarco/endoplasmic reticulum calcium ATPase activity is unchanged despite increased myofilament calcium sensitivity in Zucker type 2 diabetic fatty rat heart.

Systolic and diastolic dysfunction in diabetes have frequently been associated with abnormal calcium (Ca) regulation. However, there is emerging evidence that Ca mishandling alone is insufficient to fully explain diabetic heart dysfunction, with focus shifting to the properties of the myofilament proteins. Our aim was to examine the effects of diabetes on myofilament Ca sensitivity and Ca handling in left ventricular tissues isolated from the same type 2 diabetic rat hearts.

Identifying sex differences in predictors of epicardial fat cell morphology.

Predictors of overall epicardial adipose tissue deposition have been found to vary between males and females. Whether similar sex differences exist in epicardial fat cell morphology is currently unknown. This study aimed to determine whether epicardial fat cell size is associated with different clinical measurements in males and females.

Stage-specific regulation of signalling pathways to differentiate pluripotent stem cells to cardiomyocytes with ventricular lineage.

Background: Pluripotent stem cells (PSCs) can be an ideal source of differentiation of cardiomyocytes in vitro and during transplantation to induce cardiac regeneration. However, differentiation of PSCs into a heterogeneous population is associated with an increased incidence of arrhythmia following transplantation. We aimed to design a protocol to drive PSCs to a ventricular lineage by regulating Wnt and retinoic acid (RA) signalling pathways.

Estimating heart mass from heart volume as measured from post-mortem computed tomography.

Heart mass can be predicted from heart volume as measured from post-mortem computed tomography (PMCT), but with limited accuracy. Although related to heart mass, age, sex, and body dimensions have not been included in previous studies using heart volume to estimate heart mass. This study aimed to determine whether heart mass estimation can be improved when age, sex, and body dimensions are used as well as heart volume.

Regulation of cardiac ryanodine receptor function by the cyclic-GMP dependent protein kinase G.

Background: The cGMP-dependent protein kinase G (PKG) phosphorylates the cardiac ryanodine receptor (RyR2) . We aimed to determine whether modulation of endogenous PKG alters RyR2-mediated spontaneous Ca release and whether this effect is linked to a change in RyR2 phosphorylation.

Methods: & Results: Human embryonic kidney (HEK293) cells with inducible RyR2 expression were treated with the cGMP analogue 8-Br-cGMP (100 μM) to activate endogenous PKG.

Thiamine increases resident endoglin positive cardiac progenitor cells and atrial contractile force in humans: A randomised controlled trial.

Background: The heart has an intrinsic ability to regenerate, orchestrated by progenitor or stem cells. However, the relative complexity of non-resident cardiac progenitor cell (CPC) therapy makes modulation of resident CPCs a more attractive treatment target. Thiamine analogues improve resident CPC function in pre-clinical models.

Increased neuronal activation in sympathoregulatory regions of the brain and spinal cord in type 2 diabetic rats.

Increased cardiac sympathetic nerve activity in type 2 diabetes mellitus (DM) suggests impaired autonomic control of the heart. However, the central regions that contribute to the autonomic cardiac pathologies in type 2 DM are unknown. Therefore, we tested the hypothesis that neuronal activation would be increased in central sympathoregulatory areas in a pre-clinical type 2 DM animal model.

Long-chain acylcarnitine 18:1 acutely increases human atrial myocardial contractility and arrhythmia susceptibility.

Long-chain acylcarnitines (LCACs) are known to directly alter cardiac contractility and electrophysiology. However, the acute effect of LCACs on human cardiac function is unknown. We aimed to determine the effect of LCAC 18:1, which has been associated with cardiovascular disease, on the contractility and arrhythmia susceptibility of human atrial myocardium.

Human Atrial Fibrillation Is Not Associated With Remodeling of Ryanodine Receptor Clusters.

The release of Ca by ryanodine receptor (RyR2) channels is critical for cardiac function. However, abnormal RyR2 activity has been linked to the development of arrhythmias, including increased spontaneous Ca release in human atrial fibrillation (AF). Clustering properties of RyR2 have been suggested to alter the activity of the channel, with remodeling of RyR2 clusters identified in pre-clinical models of AF and heart failure.

Elevated myocardial fructose and sorbitol levels are associated with diastolic dysfunction in diabetic patients, and cardiomyocyte lipid inclusions in vitro.

Diabetes is associated with cardiac metabolic disturbances and increased heart failure risk. Plasma fructose levels are elevated in diabetic patients. A direct role for fructose involvement in diabetic heart pathology has not been investigated.

Long-Chain Acylcarnitines and Cardiac Excitation-Contraction Coupling: Links to Arrhythmias.

A growing number of metabolomic studies have associated high circulating levels of the amphiphilic fatty acid metabolites, long-chain acylcarnitines (LCACs), with cardiovascular disease (CVD) risk. These studies show that plasma LCAC levels can be correlated with the stage and severity of CVD and with indices of cardiac hypertrophy and ventricular function. Complementing these recent clinical associations is an extensive body of basic research that stems mostly from the twentieth century.

Inotropic and lusitropic, but not arrhythmogenic, effects of adipocytokine resistin on human atrial myocardium.

The adipocytokine resistin is released from epicardial adipose tissue (EAT). Plasma resistin and EAT deposition are independently associated with atrial fibrillation. The EAT secretome enhances arrhythmia susceptibility and inotropy of human myocardium.

Correlation between epicardial adipose tissue and body mass index in New Zealand ethnic populations.

Aim: We aimed to investigate the correlation between epicardial adipose tissue (EAT) and body mass index (BMI) in different ethnic groups in New Zealand.

Methods: The study included 205 individuals undergoing open heart surgery. Māori and Pacific groups were combined to increase statistical power.

Ventricular Weight Increases Proportionally With Total Heart Weight in Postmortem Population.

Heart weight is routinely measured at postmortem examination and is critical to determine whether the heart is enlarged (ie, cardiomegaly). Cardiomegaly has the potential to cause sudden death by being electrically unstable, resulting in fatal arrhythmias. The majority of fatal cardiac arrhythmias is ventricular in origin and is assumed that ventricular size is disproportionately larger in cardiomegaly.

Carvedilol and metoprolol are both able to preserve myocardial function in type 2 diabetes.

Purpose: Increasing cohorts of patients present with diabetic cardiomyopathy, and with no targeted options, treatment often rely on generic pharmaceuticals such as β-blockers. β-blocker efficacy is heterogenous, with second generation β-blocker metoprolol selectively inhibiting β -AR, while third generation β-blocker carvedilol has α -AR inhibition, antioxidant, and anti-apoptotic actions alongside nonselective β-AR inhibition. These additional properties have led to the hypothesis that carvedilol may improve cardiac contractility in the diabetic heart to a greater extent than metoprolol.

Relationship between epicardial adipose tissue thickness and epicardial adipocyte size with increasing body mass index.

Macroscopic deposition of epicardial adipose tissue (EAT) has been strongly associated with numerous indices of obesity and cardiovascular disease risk. In contrast, the morphology of EAT adipocytes has rarely been investigated. We aimed to determine whether obesity-driven adipocyte hypertrophy, which is characteristic of other visceral fat depots, is found within EAT adipocytes.

Acute interaction between human epicardial adipose tissue and human atrial myocardium induces arrhythmic susceptibility.

Epicardial adipose tissue (EAT) deposition has a strong clinical association with atrial arrhythmias; however, whether a direct functional interaction exists between EAT and the myocardium to induce atrial arrhythmias is unknown. Therefore, we aimed to determine whether human EAT can be an acute trigger for arrhythmias in human atrial myocardium. Human trabeculae were obtained from right atrial appendages of patients who have had cardiac surgery ( = 89).

Myocardial tissue characterisation using echocardiographic deformation imaging.

Myocardial pathology results in significant morbidity and mortality, whether due to primary cardiomyopathic processes or secondary to other conditions such as ischemic heart disease. Cardiac imaging techniques characterise the underlying tissue directly, by assessing a signal from the tissue itself, or indirectly, by inferring tissue characteristics from global or regional function. Cardiac magnetic resonance imaging is currently the most investigated imaging modality for tissue characterisation, but, due to its accessibility, advanced echocardiography represents an attractive alternative.

Epicardial adipocyte size does not correlate with body mass index.

Background: Epicardial adipose tissue (EAT) deposition has a strong association with aspects of metabolic dysfunction, including obesity. The size of the EAT adipocytes in relation to obesity, however, has rarely been researched. Therefore, to contextualise EAT within the broader framework of pathophysiological adipocyte size changes in obesity, we aimed to determine whether EAT adipocyte size is associated with body mass index (BMI).