Hyperpolarized 13 C and 31 P MRS detects differences in cardiac energetics, metabolism, and function in obesity, and responses following treatment

Obesity is associated with important changes in cardiac energetics and function, and an increased risk of adverse cardiovascular outcomes. Multi‐nuclear MRS and MRI techniques have the potential to provide a comprehensive non‐invasive assessment of cardiac metabolic perturbation in obesity. A rat model of obesity was created by high‐fat diet feeding. This model was characterized using in vivo hyperpolarized [1‐13C]pyruvate and [2‐13C]pyruvate MRS, echocardiography and perfused heart 31P MRS. Two groups of obese rats were subsequently treated with either caloric restriction or the glucagon‐like peptide‐1 analogue/agonist liraglutide, prior to reassessment. The model recapitulated cardiovascular consequences of human obesity, including mild left ventricular hypertrophy, and diastolic, but not systolic, dysfunction. Hyperpolarized 13C and 31P MRS demonstrated that obesity was associated with reduced myocardial pyruvate dehydrogenase flux, altered cardiac tricarboxylic acid (TCA) cycle metabolism, and impaired myocardial energetic status (lower phosphocreatine to adenosine triphosphate ratio and impaired cardiac ΔG~ATP). Both caloric restriction and liraglutide treatment were associated with normalization of metabolic changes, alongside improvement in cardiac diastolic function. In this model of obesity, hyperpolarized 13C and 31P MRS demonstrated abnormalities in cardiac metabolism at multiple levels, including myocardial substrate selection, TCA cycle, and high‐energy phosphorus metabolism. Metabolic changes were linked with impairment of diastolic function and were reversed in concert following either caloric restriction or liraglutide treatment. With hyperpolarized 13C and 31P techniques now available for human use, the findings support a role for multi‐nuclear MRS in the development of new therapies for obesity

Hyperpolarized 13C and 31P magnetic resonance spectroscopy detect differences in cardiac energetics, metabolism and function in obesity, and responses following treatment

BackgroundObesity is associated with important changes in cardiac energetics and function, and an increased risk of adverse cardiovascular outcomes. Multi-nuclear magnetic resonance spectroscopy and imaging techniques have the potential to provide a comprehensive non-invasive assessment of cardiac metabolic perturbation in obesity.Methods A rat model of obesity was created by high fat diet (HFD) feeding. This model was characterised using in vivo hyperpolarized [1-13C]pyruvate and [2-13C]pyruvate magnetic resonance spectroscopy (MRS), echocardiography, and perfused heart 31P MRS. Two groups of obese rats were subsequently treated with either caloric restriction or the glucagon like-peptide (GLP)-1 analog/agonist Liraglutide, prior to reassessment. ResultsThe model recapitulated cardiovascular consequences of human obesity, including mild left ventricular (LV) hypertrophy and diastolic, but not systolic, dysfunction. Hyperpolarized 13C and 31P MRS demonstrated that obesity was associated with reduced myocardial pyruvate dehydrogenase (PDH) flux, altered cardiac tricarboxylic acid cycle (TCA) metabolism, and impaired myocardial energetic status (lower phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio and impaired cardiac ΔG~ATP). Both caloric restriction and Liraglutide treatment were associated with normalisation of metabolic changes, alongside improvement in cardiac diastolic function.ConclusionsIn this model of obesity, hyperpolarized 13C and 31P MRS demonstrated abnormalities in cardiac metabolism at multiple levels, including myocardial substrate selection, TCA cycle, and high energy phosphorus metabolism. Metabolic changes were linked with impairment of diastolic function, and were reversed in concert following either caloric restriction or Liraglutide treatment. With hyperpolarized 13C and 31P techniques now available for human use, the findings support a role for multi-nuclear MRS in the development of new therapies for obesity. <br/

Relationship of cardiac remodeling and perfusion alteration with hepatic lipid metabolism in a prediabetic high fat high sucrose diet female rat model

Background and Aims: Cardiovascular disease (CVD) is known to be linked with metabolic associated fatty liver disease and type 2 diabetes, but few studies assessed this relationship in prediabetes, especially among women, who are at greater risk of CVD. We aimed to evaluate cardiac alterations and its relationship with hepatic lipid metabolism in prediabetic female rats submitted to high-fat-high-sucrose diet (HFS). Methods and Results: Wistar female rats were divided into 2 groups fed for 5 months with standard or HFS diet. We analyzed cardiac morphology, function, perfusion and fibrosis by Magnetic Resonance Imaging. Hepatic lipid contents along with inflammation and lipid metabolism gene expression were assessed. Five months of HFS diet induced glucose intolerance (p<0.05), cardiac remodeling characterized by increased left-ventricular volume, wall thickness and mass (p<0.05). No significant differences were found in left-ventricular ejection fraction and cardiac fibrosis but increased myocardial perfusion (p<0.01) and reduced cardiac index (p<0.05) were shown. HFS diet induced hepatic lipid accumulation with increased total lipid mass (p<0.001) and triglyceride contents (p<0.05), but also increased mitochondrial (CPT1a, MCAD; (p<0.001; p<0.05) and peroxisomal (ACO, LCAD; (p<0.05; p<0.001) β-oxidation gene expression. Myocardial wall thickness and perfusion were correlated with hepatic β-oxidation genes expression. Furthermore, myocardial perfusion was also correlated with hepatic lipid content and glucose intolerance. Conclusion: This study brings new insights on the relationship between cardiac su

Heart transplantation with donation after circulatory determination of death.

The constant shortage of available organs is a major obstacle and limiting factor in heart transplantation; the discrepancy between the number of donors and potential recipients leads to waiting-list mortality of 10-12% per year in Europe and the USA. If adopted for heart transplantation, donation after circulatory determination of death (DCDD) would be expected to improve the availability of organs substantially for both adults and children. With DCDD, however, hearts to be transplanted undergo a period of warm ischaemia before procurement, which is of particular concern because tissue damage occurs rapidly and might be sufficient to preclude transplantation. Nonetheless, the heart is able to withstand limited periods of warm ischaemia, which could provide a window of opportunity for DCDD. Development of clinical approaches specifically for DCDD is critical for the exploitation of these organs, because current practices for donor heart procurement, evaluation, and storage have been optimized for conventional donation after brain death, without consideration of warm ischaemia before organ procurement. Establishment of clinical protocols and ethical and legal frameworks for DCDD of other organs is underway. This Review provides a timely evaluation of the potential for DCDD in heart transplantation