Abstract
Background and aims
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.
Methods and results
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.
Conclusion
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.
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Acknowledgments
The current study was supported by a grant by the European Association for the Study of Diabetes (EASD) and by a liberal donation from the family of Angela Musazzi and Mario Stellato.
Conflict of interest
Gianluca Perseghin received lecture fees during the last 3 years from Lilly, Sigma-Tau, AstraZeneca, Takeda, Bristol Myers Squibb, Sanofi-Aventis, Merck and Co/Schering Plough, Novo Nordisk, Novartis. Gabriele Fragasso received lecture fees during the last 3 years from Servier International, Boehringer Ingelheim. Anna Salerno, Antonio Esposito, Tamara Canu, Guido Lattuada, Giuseppina Manzoni, Alessandro Del Maschio, Alberto Margonato, Francesco De Cobelli declare that they have no conflict of interest to disclose.
Ethical standard
The protocol was approved by the Ethical Committee of the Istituto Scientifico H San Raffaele.
Human and animal rights
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5).
Informed consent
Informed consent was obtained from all subjects after explanation of purposes, nature and potential risks of the study.
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Salerno, A., Fragasso, G., Esposito, A. et al. 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. Acta Diabetol 52, 753–761 (2015). https://doi.org/10.1007/s00592-014-0695-7
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DOI: https://doi.org/10.1007/s00592-014-0695-7