Mitochondrial Preference for Short Chain Fatty Acid Oxidation During Coronary Artery Constriction

Lewandowski, E. Douglas; Kudej, Raymond K.; White, Lawrence T.; O’Donnell, J. Michael; Vatner, Stephen F.

doi:10.1161/hc0302.102594

Cited by 40 publications

(29 citation statements)

References 38 publications

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“…112,113,117,119–124 Coronary artery infusion of saline solution containing 13 C-enriched fats or carbohydrates allows precise measurements of cardiac substrate utilization in the open-chest animal model, and more recently in the conscious, closed-chest pig model that is fully instrumented. 113,120 However, by definition, metabolic flux rates require multiple time points and therefore multiple sets of NMR spectra.…”

Section: C Mrs (Nmr)mentioning

confidence: 99%

Assessing Cardiac Metabolism

Taegtmeyer¹,

Young²,

Lopaschuk³

et al. 2016

Circulation Research

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237

147

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In a complex system of interrelated reactions, the heart converts chemical energy to mechanical energy. Energy transfer is achieved through coordinated activation of enzymes, ion channels, and contractile elements, as well as structural and membrane proteins. The heart’s needs for energy are difficult to overestimate. At a time when the cardiovascular research community is discovering a plethora of new molecular methods to assess cardiac metabolism, the methods remain scattered in the literature. The present statement on “Assessing Cardiac Metabolism” seeks to provide a collective and curated resource on methods and models used to investigate established and emerging aspects of cardiac metabolism. Some of those methods are refinements of classic biochemical tools, whereas most others are recent additions from the powerful tools of molecular biology. The aim of this statement is to be useful to many and to do justice to a dynamic field of great complexity.

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Section: C Mrs (Nmr)mentioning

confidence: 99%

Assessing Cardiac Metabolism

Taegtmeyer¹,

Young²,

Lopaschuk³

et al. 2016

Circulation Research

Self Cite

237

147

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“…They speculated that this represented a protective mechanism that minimizes energy demand during low-flow ischemia. Although the intracellular signaling pathway responsible for this change in calcium kinetics is unclear, Lewandowski et al (13) have reported that metabolic responses in the mitochondrial oxidative pathways also respond to signals other than changes in oxygen delivery and tissue blood flow. These authors reported that in open-chest swine, myocardium perfused with a coronary stenosis preferentially oxidized short-chain fatty acids over endogenous longchain fatty acids.…”

Section: Discussionmentioning

confidence: 99%

Myocardial oxygenation and high-energy phosphate levels during K_ATP channel blockade

Zhang

From

Uğurbil

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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.-Inhibition of ATP-sensitive K ϩ (KATP) channel activity has previously been demonstrated to result in coronary vasoconstriction with decreased myocardial blood flow and loss of phosphocreatine (PCr). This study was performed to determine whether the high-energy phosphate abnormality during KATP channel blockade can be ascribed to oxygen insufficiency. Myocardial blood flow and oxygen extraction were measured in open-chest dogs during KATP channel blockade with intracoronary glibenclamide, whereas high-energy phosphates were examined with 31 P magnetic resonance spectroscopy (MRS), and myocardial deoxymyoglobin (Mb-␦) was determined with 1 H MRS. Glibenclamide resulted in a 20 Ϯ 8% decrease of myocardial blood flow that was associated with a loss of phosphocreatine (PCr) and accumulation of inorganic phosphate. Mb-␦ was undetectable during basal conditions but increased to 58 Ϯ 5% of total myoglobin during glibenclamide administration. This degree of myoglobin desaturation during glibenclamide was far greater than we previously observed during a similar reduction of blood flow produced by a coronary stenosis (22% of myoglobin deoxygenated during stenosis). The findings suggest that reduction of coronary blood flow with an arterial stenosis was associated with a decrease of myocardial energy demands and that this response to hypoperfusion was inhibited by KATP channel blockade. blood flow; myoglobin; oxygen saturation ATP-SENSITIVE POTASSIUM (K ATP ) channels have the potential to influence energy metabolism in the heart. Opening of K ATP channels on vascular smooth muscle cells allows efflux of potassium; the resultant membrane hyperpolarization closes voltage-gated calcium channels to result in vasodilatation with an increase of blood flow (25). K ATP channels on coronary arterioles open in response to hypoxia and appear to be critical for metabolic vasoregulation by which coronary blood flow is regulated in response to myocardial metabolic requirements (11,20). We previously observed that in intact awake dogs, K ATP channel blockade with intracoronary glibenclamide resulted in vasoconstriction with a 17-20% decrease in coronary blood flow (4, 5).This decrease in coronary flow was associated with a parallel reduction of myocardial oxygen consumption (MV O 2 ) and a significant decrease of systolic wall thickening. These findings suggested that glibenclamide resulted in coronary vasoconstriction with a decrease in myocardial blood flow sufficient to result in ischemic contractile dysfunction. However, an alternative possibility is that glibenclamide caused a primary decrease of MV O 2 so that the reduction of coronary flow occurred secondary to the decreased oxygen uptake. This possibility is based on studies of K ATP channels located on the inner mitochondrial membrane where they have the potential to influence respiration and ATP synthesis (10, 15). If blockade of mitochondrial K ATP channels by glibenclamide caused a decrease of MV O 2 , then the consequent reduction of ATP synthesis could lead to decreased ...

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“…Several studies suggest that Akt may inhibit fatty acid oxidation through inhibition of PPAR-a/PCG-1-dependent transcription [98] [99]. Increased oxidation of glucose and lactate through activation of the pyruvate dehydrogenase complex (PDC) may, in turn, enhance contractile function in the setting of ischemia [100]. The anti-apoptotic effect of insulin therapy may also be explained through its effect on preserving the pro-apoptotic peptide BAD in an inactive form [91].…”

Section: Metabolic Features Of Programed Cell Survivalmentioning

confidence: 99%

Return to the fetal gene program protects the stressed heart: a strong hypothesis

et al. 2007

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A common feature of the hemodynamically or metabolically stressed heart is the return to a pattern of fetal metabolism. A hallmark of fetal metabolism is the predominance of carbohydrates as substrates for energy provision in a relatively hypoxic environment. When the normal heart is exposed to an oxygen rich environment after birth, energy substrate metabolism is rapidly switched to oxidation of fatty acids. This switch goes along with the expression of "adult" isoforms of metabolic enzymes and other proteins. However, the heart retains the ability to return to the "fetal" gene program. Specifically, the fetal gene program is predominant in a variety of pathophysiologic conditions including hypoxia, ischemia, hypertrophy, and atrophy. A common feature of all of these conditions is extensive remodeling, a decrease in the rate of aerobic metabolism in the cardiomyocyte, and an increase in cardiac efficiency. The adaptation is associated with a whole program of cell survival under stress. The adaptive mechanisms are prominently developed in hibernating myocardium, but they are also a feature of the failing heart muscle. We propose that in failing heart muscle at a certain point the fetal gene program is no longer sufficient to support cardiac structure and function. The exact mechanisms underlying the transition from adaptation to cardiomyocyte dysfunction are still not completely understood.

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Mitochondrial Preference for Short Chain Fatty Acid Oxidation During Coronary Artery Constriction

Cited by 40 publications

References 38 publications

Assessing Cardiac Metabolism

Assessing Cardiac Metabolism

Myocardial oxygenation and high-energy phosphate levels during K_ATP channel blockade

Return to the fetal gene program protects the stressed heart: a strong hypothesis

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Mitochondrial Preference for Short Chain Fatty Acid Oxidation During Coronary Artery Constriction

Cited by 40 publications

References 38 publications

Assessing Cardiac Metabolism

Assessing Cardiac Metabolism

Myocardial oxygenation and high-energy phosphate levels during KATP channel blockade

Return to the fetal gene program protects the stressed heart: a strong hypothesis

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Myocardial oxygenation and high-energy phosphate levels during K_ATP channel blockade