Effect of Left Ventricular Hypertrophy Secondary to Chronic Pressure Overload on Transmural Myocardial 2-Deoxyglucose Uptake

Zhang, Jianyi; Duncker, Dirk J.; Xu, Yawei; Zhang, Yi; Pavek, Todd; Wei, Horan; Merkle, Hellmut; Uğurbil, Kâmil; From, Arthur H. L.; Bache, Robert J.

doi:10.1161/01.cir.92.5.1274

Cited by 74 publications

(48 citation statements)

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“…In hearts with cardiac hypertrophy, we have previously reported that myocardial PCr/ATP is significantly decreased, which is linearly related to the severity of hypertrophy and LV dysfunction and is independent from a persistent myocardial ischemia (35)(36)(37)39). These LVH hearts are also associated with a significant lower myocardial total creatine level (36 -39), which, in principle, can cause the reduction of the myocardial creatine phosphate level.…”

Section: Discussionmentioning

confidence: 94%

Long-term functional improvement and gene expression changes after bone marrow-derived multipotent progenitor cell transplantation in myocardial infarction

Jameel

Mansoor

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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. Long-term functional improvement and gene expression changes after bone marrow-derived multipotent progenitor cell transplantation in myocardial infarction. Am J Physiol Heart Circ Physiol 298: H1348 -H1356, 2010. First published February 19, 2010 doi:10.1152/ajpheart.01100.2009The study examined the longterm outcome of cardiac stem cell transplantation in hearts with postinfarction left ventricular (LV) remodeling. Myocardial infarction (MI) was created by ligating the first and second diagonal branches of the left anterior descending coronary artery in miniature swines. Intramyocardial injections of 50 million LacZ-labeled bone marrowderived multipotent progenitor cells (MPC) were performed in the periscar region (Cell, n ϭ 7) immediately after MI, whereas, in control animals (Cont, n ϭ 7), saline was injected. Functional outcome was assessed monthly for 4 mo with MRI and 31 P-magnetic resonance spectroscopy. Engraftment was studied on histology, and gene chip (Affymetrix) array analysis was used to study differential expression of genes in the two groups. MPC treatment resulted in improvement of ejection fraction as early as 10 days after MI (Cell, 43.4 Ϯ 5.1% vs. Cont, 32.2 Ϯ 5.5%; P Ͻ 0.05). This improvement was seen each month and persisted to 4 mo (Cell, 51.2 Ϯ 4.8% vs. Cont, 35.7 Ϯ 5.0%; P Ͻ 0.05). PCr-to-ATP ratio (PCr/ATP) improved with MPC transplantation, which was most pronounced at high cardiac work states (subendocardial PCr/ATP was 1.70 Ϯ 0.10 vs. 1.34 Ϯ 0.14, P Ͻ 0.05). There was no significant difference in scar size (scar/LV area ‫ء‬ 100) at 10 days postinfarction. However, at 4 mo, there was a significant decrease in scar size in the Cell group (Cell, 4.6 Ϯ 1.0% vs. Cont, 8.6 Ϯ 2.4%; P Ͻ 0.05). No significant engraftment of MPC was observed. MPC transplantation was associated with a downregulation of mitochondrial oxidative enzymes and increased levels of myocyte enhancer factor 2a and zinc finger protein 91. In conclusion, MPC transplantation leads to long-term functional and bioenergetic improvement in a porcine model of postinfarction LV remodeling, despite no significant engraftment of stem cells in the heart. MPC transplantation reduces regional wall stresses and infarct size and mitigates the adverse effects of LV remodeling, as seen by a reduction in LV hypertrophy and LV dilatation, and is associated with differential expression of genes relating to metabolism and apoptosis.energetics; metabolism; heart failure; scar size STEM CELL TRANSPLANTATION has emerged as a potential therapy for limiting postinfarction left ventricular (LV) remodeling and the consequent development of congestive heart failure in both animal (1,13,15,33) and clinical (2, 3, 12, 24, 31) studies.Clinical studies have shown mixed results on LV function with stem cell therapy, with some showing benefit (3, 24, 31) and some no difference in LV ejection fraction (12,14). In the bone marrow transfer to enhance ST-elevation infarct regeneration study, the treated group showed significant short-term increase of LV eje...

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Section: Discussionmentioning

confidence: 94%

Long-term functional improvement and gene expression changes after bone marrow-derived multipotent progenitor cell transplantation in myocardial infarction

Jameel

Mansoor

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…One of the primary functions of AMPK activation is to induce glucose uptake, which has been observed in hypertrophied hearts of animal models ( 165 ) and humans ( 166 ), suggesting a functional role of AMPK in cardiac hypertrophy ( 162,167 ) and ischemia ( 168,169 ). Further evidence of AMPK in cardiac function comes from AMPK mutation that leads to myocardial metabolic storage disease with coexistence of hypertrophy and defects in conduction system ( 167 ).…”

Section: Role Of Ampk In Cardiac Functionmentioning

confidence: 99%

AMP-activated protein kinase: an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases

Srivastava

Pinkosky

Filippov

et al. 2012

Journal of Lipid Research

253

179

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This article is available online at http://www.jlr.org termed as metabolic syndrome (MetS) ( 1 ), characterized by a clustering of major risk factors for developing cardiovascular disease. Obesity, representing derangement in energy balances, is tightly linked with the development of type-2 diabetes through its ability to engender insulin resistance, leading to glucose intolerance and development of type-2 diabetes and dyslipidemia. Thus, insulin resistance The pathophysiology of diabetes and obesity is a very complex process involving many pathways. Deregulation of these pathways gives rise to metabolic abnormalities

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“…50 It is now widely accepted that glucose uptake and utilization increase in hypertrophied and mildly failing heart. [51][52][53][54] It is not yet clear how long this is sustained.…”

Section: On the Failure Of Atp Synthesis Pathways To Prevent The Decrmentioning

confidence: 99%

Is the Failing Heart Energy Starved?

Ingwall

Weiss

2004

Circulation Research

546

281

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Abstract-The requirement of chemical energy in the form of ATP to support systolic and diastolic work of the heart is absolute. Because of its central role in cardiac metabolism and performance, the subject of this review on energetics in the failing heart is ATP. We briefly review the basics of myocardial ATP metabolism and describe how this changes in the failing heart. We present an analysis of what is now known about the causes and consequences of these energetic changes and conclude by commenting on unsolved problems and opportunities for future basic and clinical research. Key Words: adenosine triphosphate Ⅲ phosphocreatine Ⅲ creatine kinase Ⅲ familial hypertrophic cardiomyopathy Ⅲ heart failure T he energy starvation hypothesis suggesting that the failing heart is energy-starved is decades old. 1,2 Because ATP is required for normal systolic and diastolic contractile performance, the idea that the failing heart is unable to meet the hemodynamic requirements of the body because there is not enough chemical energy available is logical. The hypothesis was initially set aside for several reasons. First, it was unclear whether the concentration of ATP ([ATP]) decreased. Second, it was reasoned that even if there were decreases in [ATP] in the failing heart, the remaining ATP should be sufficient to supply the ATP-requiring reactions in the myocyte. Third, our understanding of how ATP synthesis and use are regulated was remarkably incomplete. A good example of our ignorance about cardiac energetics was the use of inotropic agents to increase performance of the failing human heart. While increasing performance, these agents did so at great energetic cost and often resulted in increased, rather than decreased, heart failure mortality.There is now renewed interest in the energy-starvation hypothesis. 3,4 New biophysical tools such as nuclear magnetic resonance (NMR) spectroscopy, positron emission tomography (PET), and transgenesis using the mouse have allowed old questions to be revisited and new ones to be formulated. Combining old and new strategies to address the "energy starvation" hypothesis, we have learned much. We now know when and by how much [ATP] decreases in the hypertrophied and failing heart. We now know that despite increases in some ATP synthesizing pathways such as glycolysis, other pathways such as the creatine kinase (CK)-phosphocreatine (PCr) system decrease. Finally, we now have a better understanding of how the myocyte accomplishes the tasks of maintaining (near) normal ATP supply Original

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Effect of Left Ventricular Hypertrophy Secondary to Chronic Pressure Overload on Transmural Myocardial 2-Deoxyglucose Uptake

Abstract: The pressure-overloaded hypertrophied left ventricle demonstrated increased accumulation of 2DGP detected with 31P NMR spectroscopy. Accumulation of 2DGP was positively correlated with the degree of hypertrophy and was most marked in the subendocardium.

Cited by 74 publications

References 35 publications

Long-term functional improvement and gene expression changes after bone marrow-derived multipotent progenitor cell transplantation in myocardial infarction

Long-term functional improvement and gene expression changes after bone marrow-derived multipotent progenitor cell transplantation in myocardial infarction

AMP-activated protein kinase: an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases

Is the Failing Heart Energy Starved?

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