Metabolic modulation of myocardial ischemia

Jani, Sonal; Bergmann, Steven R.

doi:10.1007/s11886-006-0023-0

Cited by 6 publications

(7 citation statements)

References 44 publications

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“…It is entirely conceivable that fatty acids can serve as a more efficient fuel during IR 33 . On the other hand, metabolic modulators shifting metabolism preferentially to glucose utilization are a newer class of drugs to ameliorate IR injury 34 . Inhibition of fatty‐acid oxidation by etomoxir, for example, has been shown to be highly protective in hearts 35 .…”

Section: Discussionmentioning

confidence: 99%

Intralipid Increases Nitric Oxide Release from Human Endothelial Cells During Oxidative Stress

Weihrauch

Shumpert

Larson

et al. 2020

J Parenter Enteral Nutr

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Background Intralipid (ILP), a lipid emulsion, protects organs against ischemia/reperfusion (IR) injury. We hypothesized that ILP activates endothelial nitric oxide synthase (eNOS) and increases NO release from endothelial cells (ECs) through a fatty‐acid translocase cluster of differentiation (CD36) mediated endocytotic mechanism, acting as a potentially protective paracrine signal during oxidative stress. Methods Human umbilical‐vein ECs were exposed to 1% ILP for 2 hours followed by oxidative stress with 0.2‐mM hydrogen peroxide for 2 hours. Western blots were conducted with anti‐CD36, dynamin‐2, src‐kinase‐1, eNOS, and phospho‐eNOS; equal protein loading was confirmed with β‐actin. CD36 immunoprecipitation was probed for caveolin‐1 to determine if CD36 and caveolin‐1 were complexed on the cell membrane. NO was measured by fluorescence of ECs. Results ILP caused a 227% increase in CD36 expression vs controls. Immunoprecipitation indicated a CD36/caveolin‐1 complex on ECs’ membrane with exposure to ILP. Dynamin‐2 increased 52% and src‐kinase‐1 340% after ILP treatment vs control cells. eNOS phosphorylation was confirmed by a 63% increase in the phospho‐eNOS/eNOS ratio in ILP‐treated cells, and NO fluorescence increased 102%. Conclusion ILP enters ECs via endocytosis by a CD36/caveolin‐1 cell membrane receptor complex, which in turn is pulled into the cell by dynamin‐2 activity. Upregulation of src‐kinase‐1 and eNOS phosphorylation suggest downstream mediators. Subsequent NO release from ECs serve as a paracrine signal to neighboring cells for protection against IR injury. Student t‐test was utilized for single comparisons and analysis of variance with Bonferroni‐Dunn post hoc modification for multiple comparisons; P < .05 was considered statistically significant.

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Section: Discussionmentioning

confidence: 99%

Intralipid Increases Nitric Oxide Release from Human Endothelial Cells During Oxidative Stress

Weihrauch

Shumpert

Larson

et al. 2020

J Parenter Enteral Nutr

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“…The latter is in line with the present findings in Langendorff-prepared hearts from AGS where 1% Intralipid™ clearly improved post-IR function when given before and after IR. The role of glucose versus fatty acid metabolization in attenuating IR injury has indeed been the subject of a number of investigations and reviews (Jani and Bergmann 2006; Barsotti et al 2009; Jaswal et al 2011). On one side, it is entirely conceivable that fatty acids can serve as a more efficient fuel during myocardial IR (Jaswal et al 2011).…”

Section: Discussionmentioning

confidence: 99%

“…On one side, it is entirely conceivable that fatty acids can serve as a more efficient fuel during myocardial IR (Jaswal et al 2011). On the other hand, metabolic modulators shifting metabolism preferentially to glucose utilization are a newer class of drugs to ameliorate myocardial IR injury (Jani and Bergmann 2006). Inhibition of fatty acid oxidation by etomoxir, for example, has been shown to be highly cardioprotective (Lopaschuk et al 1988).…”

Section: Discussionmentioning

confidence: 99%

Lipid emulsion enhances cardiac performance after ischemia–reperfusion in isolated hearts from summer-active arctic ground squirrels

et al. 2017

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Hibernating mammals, like the arctic ground squirrel (AGS), exhibit robust resistance to myocardial ischemia/reperfusion (IR) injury. Regulated preference for lipid over glucose to fuel metabolism may play an important role. We tested whether providing lipid in an emulsion protects hearts from summer-active AGS better than hearts from Brown Norway (BN) rats against normothermic IR injury. Langendorff-prepared AGS and BN rat hearts were perfused with Krebs solution containing 7.5 mM glucose with or without 1% Intralipid™. After stabilization and cardioplegia, hearts underwent 45 minutes global ischemia and 60 minutes reperfusion. Coronary flow, isovolumetric left ventricular pressure and mitochondrial redox state were measured continuously; infarct size was measured at the end of the experiment. Glucose-only AGS hearts functioned significantly better on reperfusion than BN rat hearts. Intralipid™ administration resulted in additional functional improvement in AGS compared to glucose only and BN rat hearts. Infarct size was not different among groups. Even under non-hibernating conditions, AGS hearts performed better after IR than the best-protected rat strain. This, however, appears to strongly depend on metabolic fuel: Intralipid™ led to a significant improvement in return of function in AGS, but not in BN rat hearts, suggesting that year-round endogenous mechanisms are involved in myocardial lipid utilization that contributes to improved cardiac performance, independent of the metabolic rate decrease during hibernation. Comparative lipid analysis revealed four candidates as possible cardioprotective lipid groups. The improved function in Intralipid™-perfused AGS hearts also challenges the current paradigm that increased glucose and decreased lipid metabolism are favorable during myocardial IR.

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“…Although yielding more energy per mole of carbon, β oxidation of FAs consumes more oxygen per mole of ATP produced than does the catabolism of alternate substrates: Oxidation of 1 mol of the six-carbon FA, hexanoate, for example, generates 44 mol of ATP, whereas oxidation of the six-carbon carbohydrate, glucose, yields only 38 mol of ATP. However, oxidation of hexanoate requires 8 mol of oxygen, providing 5.5 mol of ATP for each mole of oxygen consumed, whereas only 6 mol of oxygen are needed for the complete oxidation of glucose, yielding 6.3 mol of ATP per mole of oxygen consumed [8].…”

Section: Myocardial Metabolism In Health and Diseasementioning

confidence: 99%

Fatty Acid Imaging of the Heart

Giedd

Bergmann

2011

Curr Cardiol Rep

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Imaging metabolic processes in the human heart yields valuable insights into the mechanisms contributing to myocardial pathology and allows assessment of the efficacy of therapies designed to treat cardiac disease. Recent advances in fatty acid (FA) imaging using positron emission tomography (PET) include the development of a method to assess endogenous triglyceride metabolism and the design of new fluorine-18 labeled tracers. Studies of patients with diabetes have shown that the heart is resistant to insulin-mediated glucose uptake and that metabolism of nonesterified FA is upregulated. Cardiac PET imaging has also recently shown the increase in myocardial FA uptake seen in obese patients can be reversed with weight loss. And a pilot study of patients with chronic kidney disease demonstrated that PET imaging can reveal myocardial metabolic alterations that parallel the decline in estimated glomerular filtration rate. Recent advances in FA imaging using single photon emission computed tomography (SPECT) have been accomplished with the tracer β-methyl-p-[(123)I]-iodophenyl-pentadecanoic acid (BMIPP). Two meta-analyses showed this imaging technique has a diagnostic accuracy for the detection of obstructive coronary artery disease that compares favorably with SPECT myocardial perfusion imaging and that BMIPP imaging yields excellent prognostic data in patients across the spectrum of coronary artery disease. A recent multicenter study of patients presenting with acute coronary syndromes found BMIPP SPECT imaging has greater diagnostic sensitivity than, and enhances the negative predictive value of, clinical assessment alone. Because of their exquisite sensitivity, nuclear imaging techniques facilitate the study of physiologic processes that are the key to our understanding of cardiac metabolism in health and disease.

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Metabolic modulation of myocardial ischemia

Cited by 6 publications

References 44 publications

Intralipid Increases Nitric Oxide Release from Human Endothelial Cells During Oxidative Stress

Intralipid Increases Nitric Oxide Release from Human Endothelial Cells During Oxidative Stress

Lipid emulsion enhances cardiac performance after ischemia–reperfusion in isolated hearts from summer-active arctic ground squirrels

Fatty Acid Imaging of the Heart

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