Left Ventricular Energy Metabolism Research Articles

Effects of short-term manipulation of serum FFA concentrations on left ventricular energy metabolism and function in patients with heart failure: no association with circulating bio-markers of inflammation.

We wanted to assess the effects of short-term changes in serum free fatty acids (FFAs) on left ventricular (LV) energy metabolism and function in patients with heart failure and whether they correlated with circulating markers of inflammation. LV function and phosphocreatine (PCr)/ATP ratio were assessed using MR imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) in 11 men with chronic heart failure in two experimental conditions 7 days apart. Study 1: MRI and 31P-MRS were performed before and 3-4 h after i.v. bolus + continuous heparin infusion titrated to achieve a serum FFA concentration of 1.20 mM. Study 2: The same protocol was performed before and after the oral administration of acipimox titrated to achieve a serum FFA concentration of 0.20 mM. Serum concentrations of IL6, TNF-α, PAI-1, resistin, visfatin and leptin were simultaneously assessed. Serum glucose and insulin concentrations were not different between studies. The PCr/ATP ratio (percent change from baseline: +6.0 ± 16.9 and -16.6 ± 16.1 % in Study 1 and Study 2, respectively; p = 0.005) and the LV ejection fraction (-1.5 ± 4.0 and -6.9 ± 6.3 % in Study 1 and Study 2, respectively; p = 0.044) were reduced during low FFA when compared to high FFA. Serum resistin was higher during Study 1 than in Study 2 (p < 0.05 repeated measures ANOVA); meanwhile, the other adipocytokines were not different. FFA deprivation, but not excess, impaired LV energy metabolism and function within hours. Cautions should be used when sudden iatrogenic modulation of energy substrates may take place in vulnerable patients.

Endurance training or beta-blockade can partially block the energy metabolism remodeling taking place in experimental chronic left ventricle volume overload.

BackgroundPatients with chronic aortic valve regurgitation (AR) causing left ventricular (LV) volume overload can remain asymptomatic for many years despite having a severely dilated heart. The sudden development of heart failure is not well understood but alterations of myocardial energy metabolism may be contributive. We studied the evolution of LV energy metabolism in experimental AR.MethodsLV glucose utilization was evaluated in vivo by positron emission tomography (microPET) scanning of 6-month AR rats. Sham-operated or AR rats (n = 10-30 animals/group) were evaluated 3, 6 or 9 months post-surgery. We also tested treatment intervention in order to evaluate their impact on metabolism. AR rats (20 animals) were trained on a treadmill 5 times a week for 9 months and another group of rats received a beta-blockade treatment (carvedilol) for 6 months.ResultsMicroPET revealed an abnormal increase in glucose consumption in the LV free wall of AR rats at 6 months. On the other hand, fatty acid beta-oxidation was significantly reduced compared to sham control rats 6 months post AR induction. A significant decrease in citrate synthase and complex 1 activity suggested that mitochondrial oxidative phosphorylation was also affected maybe as soon as 3 months post-AR.Moderate intensity endurance training starting 2 weeks post-AR was able to partially normalize the activity of various myocardial enzymes implicated in energy metabolism. The same was true for the AR rats treated with carvedilol (30 mg/kg/d). Responses to these interventions were different at the level of gene expression. We measured mRNA levels of a number of genes implicated in the transport of energy substrates and we observed that training did not reverse the general down-regulation of these genes in AR rats whereas carvedilol normalized the expression of most of them.ConclusionThis study shows that myocardial energy metabolism remodeling taking place in the dilated left ventricle submitted to severe volume overload from AR can be partially avoided by exercise or beta-blockade in rats.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2261-14-190) contains supplementary material, which is available to authorized users.

Left ventricular function and energy metabolism in middle-aged men undergoing long-lasting sustained aerobic oxidative training

Objective: Ageing of the human heart is characterised by morphological, functional and metabolic changes. Short-term interventions and cross-sectional studies in older individuals questioned the possibility that physical exercise may reverse...

Impaired left ventricular energy metabolism in patients with hypertrophic cardiomyopathy is related to the extension of fibrosis at delayed gadolinium-enhanced magnetic resonance imaging

Objective:Areas of intramyocardial late enhancement (LE) at delayed enhanced magnetic resonance imaging (DE-MRI) and reduction of myocardial phosphocreatine (PCr)/ATP-ratio at phosphorus magnetic resonance spectroscopy (31P-MRS) are both reported in hypertrophic...

Effects of Exercise Training on Myocardial Energy Metabolism and Ventricular Function Assessed by Quantitative Phosphorus-31 Magnetic Resonance Spectroscopy and Magnetic Resonance Imaging in Dilated Cardiomyopathy

The present study investigated changes in cardiac energy metabolism and function in patients with dilated cardiomyopathy (DCM) before and after exercise training (ET) with phosphorus-31 magnetic resonance spectroscopy (MRS) in combination with magnetic resonance imaging (MRI). Exercise training might have a beneficial role on myocardial function and oxidative metabolism in DCM, but it is unclear whether the additional load on the failing heart leads to deterioration of cardiac energy metabolism. Twenty-four patients were randomized to an exercise (age 53 +/- 12 years) or a control (age 56 +/- 6 years) group. Supervised ET was performed for 2 months, followed by 6 months of self-regulated training. At baseline and 2 and 8 months, maximal exercise testing along with quantitative MRS and MRI studies were performed. The effectiveness of ET was demonstrated by a 17% increase in peak oxygen uptake (p < 0.05). Exercise training improved left ventricular (LV) end-systolic volume (p < 0.05) and LV ejection fraction (30 +/- 15% vs. 37 +/- 15%; p < 0.01) but not right ventricular parameters. The improvement in cardiac function was not accompanied by changes in cardiac high-energy phosphate concentrations; phosphocreatine, adenosine triphosphate, and the phosphocreatine/adenosine triphosphate ratio were all unchanged after training. The observation that LV function improved and LV energy metabolism remained unchanged suggests that the beneficial effect of ET on LV function is achieved without adversely affecting metabolism. These findings lend further support for the use of ET as an adjunct therapy in DCM.

Increased mediastinal fat and impaired left ventricular energy metabolism in young men with newly found fatty liver

Fatty liver is characterized by metabolic abnormalities at the liver, but also at skeletal muscle and adipose tissue sites. It is hypothesized that the heart may be suffering metabolic alterations, and this study was undertaken to ascertain whether individuals with fatty liver have left ventricular (LV) alterations of energy metabolism, structure, and function and abnormal amounts of epicardial fat as a specific marker of visceral fat accumulation. To this end we studied young, nondiabetic men matched for anthropometric features with (n = 21) or without (n = 21) fatty liver by means of (1) cardiac magnetic resonance imaging (MRI); (2) cardiac (31)P-MR spectroscopy (MRS); and (3) hepatic (1)H-MRS to assess quantitatively the intrahepatic fat (IHF) content. Insulin sensitivity was determined by the updated HOMA-2 computer model. Individuals with fatty liver showed reduced insulin sensitivity, increased serum free fatty acid (FFA), and E-selectin, abnormal adipokine concentrations, and higher blood pressure. LV morphology and systolic and diastolic functions were not different; however, in the scanned intrathoracic region, the intrapericardial (7.8 +/- 3.1 versus 5.9 +/- 2.5 cm(2); P < 0.05) and extrapericardial (11.7 +/- 6.1 versus 7.8 +/- 3.2 cm(2); P < 0.03) fat was increased in men with fatty liver compared with those without fatty liver. The phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio, a recognized in vivo marker of myocardial energy metabolism, was reduced in men with fatty liver in comparison with normals (1.85 +/- 0.35 versus 2.11 +/- 0.31; P < 0.016). In conclusion, in newly found individuals with fatty liver, fat was accumulated in the epicardial area and despite normal LV morphological features and systolic and diastolic functions, they had abnormal LV energy metabolism.

On substrate selection for ATP synthesis in the failing human myocardium

the heart is an omnivore, able to oxidize a variety of substrates to support ATP synthesis: fatty acids, glucose, lactate, and even some amino acids ([Fig. 1][1]). Substrate selection is a highly dynamic process. For example, the uptake and utilization of substrates change from being primarily

In Vivo Effects of Myocardial Creatine Depletion on Left Ventricular Function, Morphology, and Energy Metabolism—Consequences in Acute Myocardial Infarction

The failing heart is characterized by disturbed myocardial energy metabolism and creatine (Cr) depletion. The aims of this study were to in vivo evaluate the effects of Cr depletion on: a) left ventricular (LV) function and morphology during rest and stress, b) LV energy metabolism, c) catecholamine in LV and plasma content, and d) incidence of malignant ventricular arrhythmias (MVA) during acute myocardial infarction (MI). Male rats weighing approximately 200 g were used. Two groups were studied: the rats treated with Cr analogue beta-guanidinopropionic acid (BGP) (n = 25) and controls (n = 23). BGP (1 M) was administered by subcutaneously implanted osmotic minipumps over 4 weeks. The rats (BGP n = 9, control n = 12) were than examined with transthoracic echocardiography at basal and at stress conditions induced by transesophageal pacing. In vivo (31)P magnetic resonance spectroscopy (MRS) was used for evaluation of myocardial energy status (BGP n = 7, control n = 12). (31)P MRS, echocardiography and high-performance liquid chromatography analysis of myocardial Cr, total adenine nucleotides and catecholamines in myocardium and plasma were performed on noninfarcted hearts. Myocardial infarction was induced in a subgroup of animals (BGP n = 15, control n = 15) by ligation of the left coronary artery resulting in a large ( approximately 50%) anterolateral MI and acute HF. A computerized electrocardiogram tracing was obtained continuously before induction of MI and up to 60 minutes postinfarction. Qualitative and quantitative variables of ventricular arrhythmias were analyzed using arrhythmia score. Body weight (BW) was lower (P < .01), whereas LV/BW was higher (P < .01) in the BGP group. Total myocardial Cr pool was decreased for at least 50% (P < .01) compared with the controls. There was no difference in total nucleotide pool. Phosphocreatine/adenosine-3-phosphate ratio was lower in the BGP group (P < .01). LV systolic function was disturbed during rest and stress (P < .05). Similarly, LV dimensions were increased in the BGP group (P < .05). Induction of acute MI resulted in markedly increased incidence of MVA and higher mortality in the BGP group (P < .01). Myocardial Cr depletion results in functional and structural LV alterations associated with lower myocardial energy reserve. Intact myocardial Cr metabolism is important for normal LV function during basal and stress conditions. Acute MI in the setting of myocardial Cr depletion leads to excessive mortality from ventricular arrhythmias and progressive heart failure.

Abnormal Left Ventricular Energy Metabolism in Obese Men With Preserved Systolic and Diastolic Functions Is Associated With Insulin Resistance

Perturbations in cardiac energy metabolism might represent early alterations in diabetes preceding functional and pathological changes. We evaluated left ventricular (LV) structure/geometry and function in relation to energy metabolism and cardiovascular risk factors in overweight/obese men using magnetic resonance techniques. We studied 81 healthy men (aged 22-55 years, with BMI between 19 and 35 kg/m2) by means of cardiac magnetic resonance imaging and 31P-magnetic resonance spectroscopy in the resting and fasted conditions and stratified them in quartiles of BMI (cut offs: 23.2, 25.5 and 29.0 kg/m2). LV mass increased across quartiles of BMI; meanwhile, the volumes did not differ. Parameters of LV systolic and diastolic function were not different among quartiles. The phosphocreatine-to-ATP ratio was reduced across increasing quartiles of mean +/- SD BMI (2.25 +/- 0.52, 1.89 +/- 0.26, 1.99 +/- 0.38, and 1.79 +/- 0.29; P < 0.006) in association with insulin sensitivity (computer homeostasis model assessment 2 model); this relation was independent of age, BMI, blood pressure, wall mass, HDL cholesterol, triglycerides, smoking habits, and metabolic syndrome. Abnormal LV energy metabolism was detectable in obese men in the presence of normal function, supporting the hypothesis that metabolic remodeling in insulin resistant states precedes functional and structural/geometrical remodeling of the heart regardless of the onset of overt hyperglycemia.

Cross-Sectional Assessment of the Effect of Kidney and Kidney-Pancreas Transplantation on Resting Left Ventricular Energy Metabolism in Type 1 Diabetic-Uremic Patients: A Phosphorous-31 Magnetic Resonance Spectroscopy Study

To test whether left ventricular (LV) dysfunction affecting type 1 diabetic-uremic patients was associated with abnormal heart high-energy phosphates (HEPs) and to ascertain whether these alterations were also present in recipients of kidney or kidney-pancreas transplantation.Heart failure is the major determinant of mortality in patients with diabetic uremia. Both uremia and diabetes induce alterations of cardiac HEPs metabolism.Magnetic resonance imaging and phosphorous magnetic resonance spectroscopy of the LV were performed in the resting state by means of a 1.5-T clinical scanner. Eleven diabetic-uremic patients, 5 nondiabetic patients with uremia, 11 diabetic recipients of kidney transplantation, and 16 diabetic recipients of combined kidney-pancreas transplantation were studied in a cross-sectional fashion. Eleven nondiabetic recipients of kidney-only transplant and 13 healthy subjects served as control groups.Uremic patients had higher LV mass, diastolic dysfunction, and lower phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio in comparison with recipients of kidney-pancreas or nondiabetic recipients of kidney transplant. In diabetic recipients of kidney transplant the PCr/ATP ratio was higher than in uremic patients but was lower than in the controls. Recipients of combined kidney-pancreas transplant had a higher ratio than uremic patients but no difference was found in comparison with controls.Altered resting myocardial HEPs metabolism may contribute to LV dysfunction in diabetic-uremic patients. In diabetic recipients of kidney transplantation, a certain degree of LV metabolic and functional impairment was found. In combined kidney-pancreas recipients the resting LV metabolism and function were not different than in controls.