Document Detail


Suppression of circulating free fatty acids with acipimox in chronic heart failure patients changes whole body metabolism but does not affect cardiac function.
MedLine Citation:
PMID:  20709866     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Circulating free fatty acids (FFAs) may worsen heart failure (HF) due to myocardial lipotoxicity and impaired energy generation. We studied cardiac and whole body effects of 28 days of suppression of circulating FFAs with acipimox in patients with chronic HF. In a randomized double-blind crossover design, 24 HF patients with ischemic heart disease [left ventricular ejection fraction: 26 ± 2%; New York Heart Association classes II (n = 13) and III (n = 5)] received 28 days of acipimox treatment (250 mg, 4 times/day) and placebo. Left ventricular ejection fraction, diastolic function, tissue-Doppler regional myocardial function, exercise capacity, noninvasive cardiac index, NH(2)-terminal pro-brain natriuretic peptide (NT-pro-BNP), and whole body metabolic parameters were measured. Eighteen patients were included for analysis. FFAs were reduced by 27% in the acipimox-treated group [acipimox vs. placebo (day 28-day 0): -0.10 ± 0.03 vs. +0.01 ± 0.03 mmol/l, P < 0.01]. Glucose and insulin levels did not change. Acipimox tended to increase glucose and decrease lipid utilization rates at the whole body level and significantly changed the effect of insulin on substrate utilization. The hyperinsulinemic euglycemic clamp M value did not differ. Global and regional myocardial function did not differ. Exercise capacity, cardiac index, systemic vascular resistance, and NT-pro-BNP were not affected by treatment. In conclusion, acipimox caused minor changes in whole body metabolism and decreased the FFA supply, but a long-term reduction in circulating FFAs with acipimox did not change systolic or diastolic cardiac function or exercise capacity in patients with HF.
Authors:
Mads Halbirk; Helene Nørrelund; Niels Møller; Ole Schmitz; Liv Gøtzsche; Roni Nielsen; Jens Erik Nielsen-Kudsk; Søren Steen Nielsen; Torsten Toftegaard Nielsen; Hans Eiskjær; Hans Erik Bøtker; Henrik Wiggers
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2010-08-13
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  299     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2010-11-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1220-5     Citation Subset:  IM    
Affiliation:
Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark. MSHL@ki.au.dk
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Blood Glucose / metabolism
Chronic Disease
Cross-Over Studies
Double-Blind Method
Exercise Tolerance / drug effects,  physiology
Fatty Acids, Nonesterified / blood*
Female
Heart / drug effects*,  physiology
Heart Failure / blood*,  drug therapy,  physiopathology
Humans
Hypolipidemic Agents / pharmacology*,  therapeutic use
Male
Metabolism / drug effects*,  physiology
Middle Aged
Pyrazines / pharmacology*,  therapeutic use
Stroke Volume / drug effects,  physiology
Vascular Resistance / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Fatty Acids, Nonesterified; 0/Hypolipidemic Agents; 0/Pyrazines; 51037-30-0/acipimox

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