Sacubitril/valsartan preserves regional cardiac function following myocardial infarction in rats.

Aims: Sacubitril/valsartan (Sac/Val) is used for treatment of heart failure. The effect of Sac/Val on regional dysfunction following myocardial infarction (MI) remains uncertain. This study aimed at understanding the effects of Sac/Val on regional function after MI.

Inhibition of the extracellular enzyme A disintegrin and metalloprotease with thrombospondin motif 4 prevents cardiac fibrosis and dysfunction.

Aims: Heart failure is a condition with high mortality rates, and there is a lack of therapies that directly target maladaptive changes in the extracellular matrix (ECM), such as fibrosis. We investigated whether the ECM enzyme known as A disintegrin and metalloprotease with thrombospondin motif (ADAMTS) 4 might serve as a therapeutic target in treatment of heart failure and cardiac fibrosis.

Methods And Results: The effects of pharmacological ADAMTS4 inhibition on cardiac function and fibrosis were examined in rats exposed to cardiac pressure overload.

Prolonged β-adrenergic stimulation disperses ryanodine receptor clusters in cardiomyocytes and has implications for heart failure.

Ryanodine receptors (RyRs) exhibit dynamic arrangements in cardiomyocytes, and we previously showed that 'dispersion' of RyR clusters disrupts Ca homeostasis during heart failure (HF) (Kolstad et al., eLife, 2018). Here, we investigated whether prolonged β-adrenergic stimulation, a hallmark of HF, promotes RyR cluster dispersion and examined the underlying mechanisms.

The effects of geometry on stiffness measurements in high-field magnetic resonance elastography: A study on rodent cardiac phantoms.

Purpose: Cardiac magnetic resonance elastography (MRE) can be used to assess myocardial stiffness in vivo. Rodents play an important role in modern cardiovascular research, and small animal cardiac MRE may reveal important aspects of myocardial stiffness. The aim of this study was to explore the feasibility of small animal cardiac MRE through investigation of stiffness measurements of small cardiac phantoms that have known underlying stiffness.

Extreme altitude induces divergent mass reduction of right and left ventricle in mountain climbers.

Mountain climbing at high altitude implies exposure to low levels of oxygen, low temperature, wind, physical and psychological stress, and nutritional insufficiencies. We examined whether right ventricular (RV) and left ventricular (LV) myocardial masses were reversibly altered by exposure to extreme altitude. Magnetic resonance imaging and echocardiography of the heart, dual x-ray absorptiometry scan of body composition, and blood samples were obtained from ten mountain climbers before departure to Mount Everest or Dhaulagiri (baseline), 13.

Impact of delayed type hypersensitivity arthritis on development of heart failure by aortic constriction in mice.

Aims: Patients with rheumatoid arthritis (RA) have increased risk of heart failure (HF). The mechanisms and cardiac prerequisites explaining this association remain unresolved. In this study, we sought to determine the potential cardiac impact of an experimental model of RA in mice subjected to HF by constriction of the ascending aorta.

One step closer to myocardial physiology: From PV loop analysis to state-of-the-art myocardial imaging.

Recent advances in cardiac imaging have revitalized the assessment of fundamental physiological concepts. In the field of cardiac physiology, invasive measurements with pressure-volume (PV) loops have served as the gold standard methodology for the characterization of left ventricular (LV) function. From PV loop data, fundamental aspects of LV chamber function are derived such as work, efficiency, stiffness and contractility.

A 4D continuous representation of myocardial velocity fields from tissue phase mapping magnetic resonance imaging.

Myocardial velocities carry important diagnostic information in a range of cardiac diseases, and play an important role in diagnosing and grading left ventricular diastolic dysfunction. Tissue Phase Mapping (TPM) Magnetic Resonance Imaging (MRI) enables discrete sampling of the myocardium's underlying smooth and continuous velocity field. This paper presents a post-processing framework for constructing a spatially and temporally smooth and continuous representation of the myocardium's velocity field from TPM data.

Etiology-Dependent Impairment of Diastolic Cardiomyocyte Calcium Homeostasis in Heart Failure With Preserved Ejection Fraction.

Background: Whereas heart failure with reduced ejection fraction (HFrEF) is associated with ventricular dilation and markedly reduced systolic function, heart failure with preserved ejection fraction (HFpEF) patients exhibit concentric hypertrophy and diastolic dysfunction. Impaired cardiomyocyte Ca homeostasis in HFrEF has been linked to disruption of membrane invaginations called t-tubules, but it is unknown if such changes occur in HFpEF.

Objectives: This study examined whether distinct cardiomyocyte phenotypes underlie the heart failure entities of HFrEF and HFpEF.

Sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload.

Aims: Sacubitril/valsartan (sac/val) has shown superior effect compared with blockade of the renin-angiotensin-aldosterone system in heart failure with reduced ejection fraction. We aimed to investigate effects of sac/val compared with valsartan in a pressure overload model of heart failure with preserved ejection fraction (HFpEF).

Methods And Results: Sprague-Dawley rats underwent aortic banding or sham (n = 16) surgery and were randomized to sac/val (n = 28), valsartan (n = 29), or vehicle (n = 26) treatment for 8 weeks.

Analysis of right ventricular mass from magnetic resonance imaging data: a simple post-processing algorithm for correction of partial-volume effects.

Magnetic resonance imaging (MRI) of the right ventricle (RV) offers important diagnostic information, but the accuracy of this information is hampered by the complex geometry of the RV. Here, we propose a novel postprocessing algorithm that corrects for partial-volume effects in the analysis of standard MRI cine images of RV mass (RVm) and evaluate the method in clinical and preclinical data. Self-corrected RVm measurement was compared with conventionally measured RVm in 16 patients who showed different clinical indications for cardiac MRI and in 17 Wistar rats with different degrees of pulmonary congestion.

Quantifying left ventricular function in heart failure: What makes a clinically valuable parameter?

In heart failure (HF) management, noninvasive quantification of left ventricular (LV) function is rapidly evolving. Deformation parameters, such as strain, continue to challenge the central role of ejection fraction (EF) in diagnosis and prognostication of LV dysfunction in HF. The increasing recognition and use of deformation parameters motivates a conceptual discussion about what makes a parameter clinically valuable.

Regional right ventricular function in rats: a novel magnetic resonance imaging method for measurement of right ventricular strain.

The function of the right ventricle (RV) is linked to clinical outcome in many cardiovascular diseases, but its role in experimental heart failure remains largely unexplored due to difficulties in measuring RV function in vivo. We aimed to advance RV imaging by establishing phase-contrast MRI (PC-MRI) as a robust method for measuring RV function in rodents. A total of 46 Wistar-Hannover rats with left ventricular (LV) myocardial infarction and 10 control rats (sham) were examined 6 wk after surgery.

Cardiovascular rEmodelling in living kidNey donorS with reduced glomerular filtration rate: rationale and design of the CENS study.

Until recently, it has been believed that donating a kidney not represents any risk for development of cardiovascular disease. However, a recent Norwegian epidemiological study suggests that kidney donors have an increased long-term risk of cardiovascular mortality. The pathophysiological mechanisms linking reduced kidney function to cardiovascular disease are not known.

Accelerated magnetic resonance imaging tissue phase mapping of the rat myocardium using compressed sensing with iterative soft-thresholding.

Introduction: Tissue Phase Mapping (TPM) MRI can accurately measure regional myocardial velocities and strain. The lengthy data acquisition, however, renders TPM prone to errors due to variations in physiological parameters, and reduces data yield and experimental throughput. The purpose of the present study is to examine the quality of functional measures (velocity and strain) obtained by highly undersampled TPM data using compressed sensing reconstruction in infarcted and non-infarcted rat hearts.

Caspase-1 induces smooth muscle cell growth in hypoxia-induced pulmonary hypertension.

Lung diseases with hypoxia are complicated by pulmonary hypertension, leading to heart failure and death. No pharmacological treatment exists. Increased proinflammatory cytokines are found in hypoxic patients, suggesting an inflammatory pathogenesis.

Regional diastolic dysfunction in post-infarction heart failure: role of local mechanical load and SERCA expression.

Aims: Regional heterogeneities in contraction contribute to heart failure with reduced ejection fraction (HFrEF). We aimed to determine whether regional changes in myocardial relaxation similarly contribute to diastolic dysfunction in post-infarction HFrEF, and to elucidate the underlying mechanisms.

Methods And Results: Using the magnetic resonance imaging phase-contrast technique, we examined local diastolic function in a rat model of post-infarction HFrEF.

Regional Dysfunction After Myocardial Infarction in Rats.

Background: Detailed understanding of regional function after myocardial infarction (MI) is currently incomplete. We aimed at investigating regional myocardial strain and work in post-MI rats with and without heart failure.

Methods And Results: Six weeks after induction of MI, 62 male Wistar-Hannover rats with a range of infarct sizes, plus 14 sham-operated rats, were examined by cine and phase-contrast magnetic resonance imaging.

Noninvasive stratification of postinfarction rats based on the degree of cardiac dysfunction using magnetic resonance imaging and echocardiography.

The myocardial infarction (MI) rat model plays a crucial role in modern cardiovascular research, but the inherent heterogeneity of this model represents a challenge. We sought to identify subgroups among the post-MI rats and establish simple noninvasive stratification protocols for such subgroups. Six weeks after induction of MI, 49 rats underwent noninvasive examinations using magnetic resonance imaging (MRI) and echocardiography.

A semiautomatic method for rapid segmentation of velocity-encoded myocardial magnetic resonance imaging data.

Purpose: To develop a semiautomatic method for rapid segmentation of myocardial tissue phase mapping (TPM) data.

Methods: Manual segmentation of the myocardium was performed at end-diastole and end-systole. The points in both user-defined masks were then automatically tracked over the entire cardiac cycle using temporal integration of the velocity field.

Elevated ventricular wall stress disrupts cardiomyocyte t-tubule structure and calcium homeostasis.

Aims: Invaginations of the cellular membrane called t-tubules are essential for maintaining efficient excitation-contraction coupling in ventricular cardiomyocytes. Disruption of t-tubule structure during heart failure has been linked to dyssynchronous, slowed Ca(2+) release and reduced power of the heartbeat. The underlying mechanism is, however, unknown.

Three-Directional Evaluation of Mitral Flow in the Rat Heart by Phase-Contrast Cardiovascular Magnetic Resonance.

Purpose: Determination of mitral flow is an important aspect in assessment of cardiac function. Traditionally, mitral flow is measured by Doppler echocardiography which suffers from several challenges, particularly related to the direction and the spatial inhomogeneity of flow. These challenges are especially prominent in rodents.