In vivo assessment of cardiac metabolism and function in the abdominal aortic banding model of compensated cardiac hypertrophy.

Aims: Left ventricular hypertrophy is an adaptive response of the heart to chronic mechanical overload and can lead to functional deterioration and heart failure. Changes in cardiac energy metabolism are considered as key to the hypertrophic remodelling process. The concurrence of obesity and hypertrophy has been associated with contractile dysfunction, and this work therefore aimed to investigate the in vivo structural, functional, and metabolic remodelling that occurs in the hypertrophied heart in the setting of a high-fat, high-sucrose, Western diet (WD).

Mitochondrial dysfunction in uremic cardiomyopathy.

Uremic cardiomyopathy (UCM) is characterized by metabolic remodelling, compromised energetics, and loss of insulin-mediated cardioprotection, which result in unsustainable adaptations and heart failure. However, the role of mitochondria and the susceptibility of mitochondrial permeability transition pore (mPTP) formation in ischemia-reperfusion injury (IRI) in UCM are unknown. Using a rat model of chronic uremia, we investigated the oxidative capacity of mitochondria in UCM and their sensitivity to ischemia-reperfusion mimetic oxidant and calcium stressors to assess the susceptibility to mPTP formation.

Uremic cardiomyopathy is characterized by loss of the cardioprotective effects of insulin.

Chronic kidney disease is associated with a unique cardiomyopathy, characterized by a combination of structural and cellular remodeling, and an enhanced susceptibility to ischemia-reperfusion injury. This may represent dysfunction of the reperfusion injury salvage kinase pathway due to insulin resistance. The susceptibility of the uremic heart to ischemia-reperfusion injury and the cardioprotective effects of insulin and rosiglitazone were investigated.

Differential induction of cellular proliferation, hypertrophy and apoptosis in H9c2 cardiomyocytes by exogenous tissue factor.

Recent evidence has shown that prolonged exposure to exogenous tissue factor (TF) can alter the cellular functions of cardiomyocytes resulting in cardiac dysfunction. The effect of TF may arise from local inflammation within or in the vicinity of the heart. The aim of this study was to investigate the effect of TF on cardiomyocyte proliferation and growth.

Microfluidic perfusion system for maintaining viable heart tissue with real-time electrochemical monitoring of reactive oxygen species.

A microfluidic device has been developed to maintain viable heart tissue samples in a biomimetic microenvironment. This device allows rat or human heart tissue to be studied under pseudo in vivo conditions. Effluent levels of lactate dehydrogenase and hydrogen peroxide were used as markers of damaged tissue in combination with in situ electrochemical measurement of the release of reactive oxygen species (ROS).

Uremic cardiomyopathy and insulin resistance: a critical role for akt?

Uremic cardiomyopathy is a classic complication of chronic renal failure whose cause is unclear and treatment remains disappointing. Insulin resistance is an independent predictor of cardiovascular mortality in chronic renal failure. Underlying insulin resistance are defects in insulin signaling through the protein kinase, Akt.

Functional and metabolic adaptation in uraemic cardiomyopathy.

Cardiovascular complications are the leading cause of death in patients with chronic kidney disease (CKD). The uraemic heart undergoes substantial remodelling, including left ventricular hypertrophy (LVH), an important determinant of heart failure. LVH results in a shift in myocardial substrate oxidation from fatty acids towards carbohydrates however, whether this metabolic adaptation occurs in the uraemic heart is unknown.

Cellular basis of uraemic cardiomyopathy: a role for erythropoietin?

The use of erythropoietin (EPO) has revolutionized the treatment of anaemia associated with many conditions including chronic kidney disease (CKD). However, little is known of the cellular impact of EPO on the uraemic heart. The discovery that the EPO receptor (EPOR) is also expressed on non-haematopoietic cells including cardiomyocytes highlights a role of EPO beyond haematopoiesis.

Insulin resistance and altered glucose transporter 4 expression in experimental uremia.

Progressive ventricular hypertrophy can lead to the development of insulin resistance, a feature of both chronic kidney disease and heart failure. Here we induced uremia in adult male Sprague-Dawley rats using a remnant kidney model and studied the expression of glucose transporters. As expected, the reduction of nephron mass resulted in impaired renal function, cardiac hypertrophy, glucose intolerance, hyperinsulinemia, anemia, and hypertension.

Western diet impairs metabolic remodelling and contractile efficiency in cardiac hypertrophy.

Aims: Metabolic remodelling in cardiac hypertrophy is underscored by a reduction in fatty acid (FA) oxidation. We tested whether this decline in FA oxidation in the presence of enhanced FA supply may predispose the hypertrophied myocardium to lipid accumulation, functional deterioration, and eventually heart failure.

Methods: and results Left ventricular hypertrophy was induced surgically in Sprague-Dawley rats by inter-renal aortic constriction.

Compensated cardiac hypertrophy is characterised by a decline in palmitate oxidation.

Cardiac hypertrophy is an independent risk factor in the development of heart failure. However, the cellular mechanisms underlying the transition from compensated hypertrophy to heart failure are incompletely understood. The aim of this study was to investigate changes in myocardial substrate utilisation and function in pressure-overload hypertrophy (using 13C NMR spectroscopy) in parallel with alterations in the expression pattern of genes involved in cardiac fatty acid and glucose uptake and oxidation.

Myocardial function, energy provision, and carnitine deficiency in experimental uremia.

Cardiac complications are the leading cause of mortality in patients with chronic renal failure. Secondary carnitine deficiency, which is frequently observed in hemodialysis patients, has been associated with cardiac hypertrophy and heart failure and may impair myocardial fatty acid oxidation. In chronic kidney disease, impaired carnitine homeostasis also may affect myocardial metabolism.

Imaging cardiac metabolism in heart failure: the potential of NMR spectroscopy in the era of metabolism revisited.

Nuclear magnetic resonance (NMR) spectroscopy remains an extremely powerful technique for investigating abnormalities in the failing heart. The nondestructive nature of the technique allows the response to physiological, pathophysiological and pharmacological interventions to be studied within the same heart. Phosphorus-31 NMR has provided a gold standard over the past two decades for assessing the myocardial energy status both in vitro and in vivo.

Metabolic remodeling in the aging heart.

The aim of this study was to investigate the effects of aging on the profile of myocardial substrate utilization and cardiac function using a physiological profile of substrates. Hearts from 6-, 15- and 24-month male Wistar rats were perfused in the isovolumic Langendorff mode, with physiological concentrations of 13C labeled palmitate, and either 13C labeled lactate or 13C glucose. 13C-NMR glutamate isotopomer analysis was performed to determine the contribution of the different substrates to oxidative metabolism.

Clinical trials update from the European Society of Cardiology Heart Failure meeting: COMET, COMPANION, Tezosentan and SHAPE.

This article continues a series of reports on recent research developments in the field of heart failure. Key presentations made at the European Society of Cardiology Heart Failure Update meeting, held in Strasbourg, France are described. The COMET study showed a 17% relative risk reduction in all-cause mortality with carvedilol compared with metoprolol tartrate.

Cardiac carbohydrate metabolism in Zucker diabetic fatty rats.

Objective: The aim of this study was to test the hypothesis that, shortly after the development of Type-2 diabetes, alterations in cardiac carbohydrate metabolism precede the onset of abnormalities in systolic function.

Methods: Hearts from 11-week-old Zucker diabetic fatty (ZDF) rats and age matched controls were perfused in the isovolumic Langendorff mode with 13C-labeled glucose, lactate and pyruvate and unlabeled fatty acids. 13C-Nuclear magnetic resonance glutamate isotopomer analysis was carried out to determine the contributions of substrates to energy production.

Attenuation of cardiac fibrosis by pirfenidone and amiloride in DOCA-salt hypertensive rats.

1. This study has administered pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) or amiloride to attenuate the remodelling and associated functional changes, especially an increased cardiac stiffness, in DOCA-salt hypertensive rats. 2.