scholarly journals Impact of anaerobic glycolysis and oxidative substrate selection on contractile function and mechanical efficiency during moderate severity ischemia

2008 ◽  
Vol 295 (3) ◽  
pp. H939-H945 ◽  
Author(s):  
Lufang Zhou ◽  
Hazel Huang ◽  
Tracy A. McElfresh ◽  
Domenick A. Prosdocimo ◽  
William C. Stanley
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Contractile Function ◽  
Mechanical Efficiency ◽  
Acid Oxidation ◽  
Anaerobic Glycolysis ◽  
Moderate Severity ◽  
Free Fatty Acid Oxidation

The role of anaerobic glycolysis and oxidative substrate selection on contractile function and mechanical efficiency during moderate severity myocardial ischemia is unclear. We hypothesize that 1) preventing anaerobic glycolysis worsens contractile function and mechanical efficiency and 2) increasing glycolysis and glucose oxidation while inhibiting free fatty acid oxidation improves contractile function during ischemia. Experiments were performed in anesthetized pigs, with regional ischemia induced by a 60% decrease in left anterior descending coronary artery blood flow for 40 min. Three groups were studied: 1) no treatment, 2) inhibition of glycolysis with iodoacetate (IAA), or 3) hyperinsulinemia and hyperglycemia (HI + HG). Glucose and free fatty acid oxidation were measured using radioisotopes and anaerobic glycolysis from net lactate efflux and myocardial lactate content. Regional contractile power was assessed from left ventricular pressure and segment length in the anterior wall. We found that preventing anaerobic glycolysis with IAA during ischemia in the absence of alterations in free fatty acid and glucose oxidation did not adversely affect contractile function or mechanical efficiency during myocardial ischemia, suggesting that anaerobic glycolysis is not essential for maintaining residual contractile function. Increasing glycolysis and glucose oxidation with HI + HG inhibited free fatty acid oxidation and improved contractile function and mechanical efficiency. In conclusion, these results show a dissociation between myocardial function and anaerobic glycolysis during moderate severity ischemia in vivo, suggesting that metabolic therapies should not be aimed at inhibiting anaerobic glycolysis per se, but rather activating insulin signaling and/or enhancing carbohydrate oxidation and/or decreasing fatty acid oxidation.

Insulin Resistance of Stress: Sites and Mechanisms

1993 ◽  
Vol 85 (5) ◽  
pp. 525-535 ◽  
Author(s):  
Luigi S. Brandi ◽  
Donatella Santoro ◽  
Andrea Natali ◽  
Fiorella Altomonte ◽  
Simona Baldi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Plasma Free Fatty Acid ◽  
Whole Body ◽  
Glucose Disposal ◽  
Acid Oxidation ◽  
Free Fatty Acid Oxidation

1. Stress is associated with a severe, yet reversible, form of insulin resistance. The aim of this study was to quantify the kinetics of insulin action (sensitivity and responsiveness) on intermediary metabolism during post-surgical stress. 2. We studied nine patients 6–8 h after major uncomplicated surgery, and eight healthy subjects matched for age, weight, glucose tolerance and duration of fast. A three-step isoglycaemic insulin clamp was combined with indirect calorimetry, [6-3H]glucose infusion and the forearm technique. 3. The following significant (P <0.05 or less) abnormalities were found in the patients. Hepatic glucose production was higher at baseline, and less suppressed by insulin. Whole-body glucose disposal was impaired at all insulin doses (by 33–60%). Glucose oxidation was depressed throughout the dose range but its increments in response to insulin were normal. In contrast, non-oxidative glucose disposal was essentially unresponsive. At all insulin levels, forearm glucose extraction was markedly depressed and forearm lactate release was in excess of concurrent glucose uptake, suggesting ongoing glycogenolysis despite insulin. Total lipolysis (plasma free fatty acid and glycerol levels) promptly responded to insulin but remained higher than in the control subjects throughout. In the forearm, even the highest insulin dose could not suppress net free fatty acid and glycerol release. Total lipid oxidation was increased throughout the insulin range, and calculated direct free fatty acid (as opposed to plasma free fatty acid) oxidation was virtually unaffected by insulin. Protein oxidation was slightly (35%) increased, but was suppressed normally in response to insulin. Energy expenditure was 20% higher at baseline, and tailed to rise with insulin. Arterial blood pH values were consistently (if slightly) lower, and net forearm proton release was higher, both at baseline and daring insulin infusion. 4. Post-surgical unsulin resistance is characterized by normal sensitivity but decreased responsiveness of glucose oxidation, lipolysis and plasma free fatty acid oxidation, whereas glycogen synthesis and direct free fatty acid oxidation are virtually unresponsive. For both glucose and lipid metabolism, the insulin resistance is particularly severe in forearm tissues, in which mild metabolic acidosis may play an additional role.

Effect of hyperglycemia and fatty acid oxidation inhibition during aerobic conditions and demand-induced ischemia

2003 ◽  
Vol 284 (5) ◽  
pp. H1521-H1527 ◽  
Author(s):  
Pedro N. Chavez ◽  
William C. Stanley ◽  
Tracy A. McElfresh ◽  
Hazel Huang ◽  
Joseph P. Sterk ◽  
...  
Keyword(s):  
Energy Efficiency ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Contractile Function ◽  
Systolic Function ◽  
Lactate Production ◽  
Acid Oxidation ◽  
Aerobic Conditions ◽  
Free Fatty Acid Oxidation

Metabolic interventions improve performance during demand-induced ischemia by reducing myocardial lactate production and improving regional systolic function. We tested the hypotheses that 1) stimulation of glycolysis would increase lactate production and improve ventricular wall motion, and 2) the addition of fatty acid oxidation inhibition would reduce lactate production and further improve contractile function. Measurements were made in anesthetized open-chest swine hearts. Three groups, hyperglycemia (HG), HG + oxfenicine (HG + Oxf), and control (CTRL), were treated under aerobic conditions and during demand-induced ischemia. During demand-induced ischemia, HG resulted in greater lactate production and tissue lactate content but had no significant effect on glucose oxidation. HG + Oxf significantly lowered lactate production and increased glucose oxidation compared with both the CTRL and HG groups. Myocardial energy efficiency was greater in the HG and HG + Oxf groups under aerobic conditions but did not change during demand-induced ischemia. Thus enhanced glycolysis resulted in increased energy efficiency under aerobic conditions but significantly enhanced lactate production with no further improvement in function during demand-induced ischemia. Partial inhibition of free fatty acid oxidation in the presence of accelerated glycolysis increased energy efficiency under aerobic conditions and significantly reduced lactate production and enhanced glucose oxidation during demand-induced ischemia.

scholarly journals Weight Reduction and the Impaired Plasma-Derived Free Fatty Acid Oxidation in Type 2 Diabetic Subjects1

2001 ◽  
Vol 86 (4) ◽  
pp. 1638-1644
Author(s):  
E. E. Blaak ◽  
B. H. R. Wolffenbuttel ◽  
W. H. M. Saris ◽  
M. M. A. L. Pelsers ◽  
A. J. M. Wagenmakers
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Weight Reduction ◽  
Acid Oxidation ◽  
Free Fatty Acid Oxidation ◽  
Type 2 Diabetic

Epinephrine increases ATP production in hearts by preferentially increasing glucose metabolism

1994 ◽  
Vol 267 (5) ◽  
pp. H1862-H1871 ◽  
Author(s):  
R. L. Collins-Nakai ◽  
D. Noseworthy ◽  
G. D. Lopaschuk
Keyword(s):  
Fatty Acid ◽  
Glucose Metabolism ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Contractile Function ◽  
Pyruvate Dehydrogenase Complex ◽  
Active Form ◽  
Acid Oxidation ◽  
Complex Activity ◽  
Atp Production

Although epinephrine is widely used clinically, its effect on myocardial energy substrate preference in the intact heart has yet to be clearly defined. We determined the effects of epinephrine on glucose and fatty acid metabolism in isolated working rat hearts perfused with 11 mM glucose, 0.4 mM palmitate, and 100 muU/ml insulin at an 11.5-mmHg left atrial preload and a 60-mmHg aortic afterload. Glycolysis and glucose oxidation were measured in hearts perfused with [5–3H]glucose and [U-14C]glucose, whereas fatty acid oxidation was measured in hearts perfused with [1–14C]palmitate. Addition of 1 microM epinephrine resulted in a 53% increase in the heart rate-developed pressure product. Glycolysis increased dramatically following addition of epinephrine (a 272% increase), as did glucose oxidation (a 410% increase). In contrast, fatty acid oxidation increased by only 10%. Epinephrine treatment did not increase the amount of oxygen required to produce an equivalent amount of ATP; however, epinephrine did increase the uncoupling between glycolysis and glucose oxidation in these fatty acid-perfused hearts, resulting in a significant increase in H+ production from glucose metabolism. Overall ATP production in epinephrine-treated hearts increased 59%. The contribution of glucose (glycolysis and glucose oxidation) to ATP production increased from 13 to 36%, which was accompanied by a reciprocal decrease in the contribution of fatty acid oxidation to ATP production from 83 to 63%. The increase in glucose oxidation was accompanied by a significant increase in pyruvate dehydrogenase complex activity in the active form. We conclude that the increase in ATP required for contractile function following epinephrine treatment occurs through a preferential increase in glucose use.

scholarly journals Modulation of Cardiac Metabolism in Heart Failure

2019 ◽  
Vol 17 ◽  
Author(s):  
Giuseppe Rosano ◽  
Andrew Coats
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Skeletal Muscles ◽  
Cardiac Metabolism ◽  
Acid Oxidation ◽  
Patients With Heart Failure ◽  
Free Fatty Acid Oxidation ◽  
Capacity Modulation

Heart failure is associated with altered cardiac metabolism, in part, due to maladaptive mechanisms, in part secondary to comorbidities such as diabetes and ischaemic heart disease. The metabolic derangements taking place in heart failure are not limited to the cardiac myocytes, but extend to skeletal muscles and the vasculature causing changes that contribute to the worsening of exercise capacity. Modulation of cardiac metabolism with partial inhibition of free fatty acid oxidation has been shown to be beneficial in patients with heart failure. At the present, the bulk of evidence for this class of drugs comes from Trimetazidine. Newer compounds partially inhibiting free fatty acid oxidation or facilitating the electron transport on the mitochondrial cristae are in early phase of their clinical development.

Validation of Tracer Estimations of Plasma Free Fatty Acid Oxidation

1994 ◽  
Vol 87 (s1) ◽  
pp. 94-95
Author(s):  
LS Sidossis ◽  
AR Coggan ◽  
A Gastaldelli ◽  
RR Wolfe
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Plasma Free Fatty Acid ◽  
Acid Oxidation ◽  
Free Fatty Acid Oxidation
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