Influence of insulin and free fatty acids on contractile function in patients with chronically stunned and hibernating myocardium

Wiggers, Henrik; Nørrelund, Helene; Nielsén, Sören; Andersen, Niels Holmark; Nielsen‐Kudsk, Jens Erik; Christiansen, Jens Sandahl; Nielsen, Torsten Toftegaard; Møller, Niels; Bøtker, Hans Erik

doi:10.1152/ajpheart.00150.2005

Cited by 20 publications

(28 citation statements)

References 58 publications

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“…Positive results have been reported in studies of glucagon-like peptide-1 (25), trimetazidine (10,31), and perhexiline (12), but most studies conducted have been small, unrandomized, and open labeled (10,25). We did not detect any acute effects of total suppression of circulating FFAs in HF patients with large areas of chronically stunned and hibernating myocardium (34), whereas others (30) have reported a decrease in stroke volume and myocardial efficiency. The proposed mechanism in prior positive studies have been effects on cardiac metabolism through increased insulin sensitivity (31), myocardial glucose uptake (18), decreased myocyte FFA mitochondrial transportation (12), or energy generation (10,31).…”

contrasting

confidence: 43%

“…Echocardiographic measurements were performed after 1 h of rest by one observer on an ultrasound scanner (Vivid Seven, GE Medical System, Horten, Norway) with a 2.5-MHz transducer and stored on the hospital server as previously described (34). Echopac analysis software (GE-Vingmed Ultrasound) was used for analysis.…”

Section: Patientsmentioning

confidence: 99%

“…Echopac analysis software (GE-Vingmed Ultrasound) was used for analysis. LVEF was assessed tracing the endocardial borders using a triplane model as previously described (34). By tissue-Doppler imaging, we measured peak systolic velocities and peak systolic strain rate during ejection time (34).…”

Section: Patientsmentioning

confidence: 99%

“…99m Tc-Sestamibi and FDG ␣-camera positron emission tomography (PET) were performed as previously described (34). We aligned the Sestamibi and FDG images with the 16 echocardiographic regions and classified regions as control, viable, or scar (34).…”

Section: Patientsmentioning

confidence: 99%

“…We aligned the Sestamibi and FDG images with the 16 echocardiographic regions and classified regions as control, viable, or scar (34). Among the final study population, four patients did not undergo single photon emission computed tomography (SPECT)/PET after completion of the protocol [myocardial infarction (n ϭ 1), amiodarone-induced thyrotoxicosis and atrial fibrillation (n ϭ 1), claustrophobia (n ϭ 1), and refusal (n ϭ 1)].…”

Section: Patientsmentioning

confidence: 99%

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Suppression of circulating free fatty acids with acipimox in chronic heart failure patients changes whole body metabolism but does not affect cardiac function

Halbirk

Nørrelund

Møller

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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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 Ϯ 2%; New York Heart Association classes II (n ϭ 13) and III (n ϭ 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, NH2-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 Ϫ day 0): Ϫ0.10 Ϯ 0.03 vs. ϩ0.01 Ϯ 0.03 mmol/l, P Ͻ 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. metabolism; insulin resistance WHOLE BODY AND CARDIAC METABOLISM are abnormal in patients with chronic heart failure (HF) and correlate with a poor prognosis (2,16,28). In HF, cardiac glucose metabolism is increased, fatty acid handling and mitochondrial enzymes are down regulated (7,8,13,23), and high-energy phosphate metabolism is reduced (27). It is debated whether these changes are causally involved in the progression of HF or represent an epiphenomenon secondary to the disease process itself (17, 32). Insulin resistance and high levels of circulating free fatty acids (FFAs) increase myocardial FFA uptake and may cause lipotoxicity and the progression of HF. Optimizing myocardial energy metabolism by targeting abnormal whole body metabolism and thereby decreasing cardiac FFAs and increasing glucose metabolism may therefore constitute a principle for treatment of patients with HF (21). Positive results have been reported in studies of glucagon-like peptide-1 (25), trimetazidine (10, 31), and perhexiline (12), but most studies conducted have been small, unrandomized, and open labeled (10, 25). We did not detect any acute effects of total suppression of circulating FFAs in HF patients with large areas of chronically stunned and hibernating myocardium (34), whereas others (30) have reported a decrease in stroke volume and myocardial efficiency. The proposed mechanism...

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contrasting

confidence: 43%

Section: Patientsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

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Suppression of circulating free fatty acids with acipimox in chronic heart failure patients changes whole body metabolism but does not affect cardiac function

Halbirk

Nørrelund

Møller

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Impact of estradiol on insulin signaling in the rat heart

Korićanac¹,

Milosavljevic²,

Stojiljković³

et al. 2009

Cell Biochemistry & Function

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It is well known that variation in the concentration of estrogens affects insulin action. In this study we examine the impact of estradiol (E2) on insulin signaling in the rat heart. Ovariectomized female rats were treated with E2 6 h prior to analysis of basal protein and mRNA content of insulin signaling molecules, and additionally with insulin 30 min before the experiment to delineate E2 effects on phosphorylations and molecular associations relevant for insulin signaling. The results show that E2 decreased insulin receptor (IR) tyrosine phosphorylation, while it did not alter IR protein and mRNA content. E2 administration did not change IR substrate 1 (IRS-1) protein content and tyrosine phosphorylation, while decreased mRNA content and increased its association with the p85 subunit of phosphatidylinositol 3-kinase (PI3K). E2 decreased protein and mRNA content of IR substrate 2 (IRS-2), while did not change IRS-2 tyrosine phosphorylation and IRS-2 association with p85. The increase of IRS-1/p85 is accompanied by increase of p85 protein and mRNA levels, and by stimulation of protein kinase B (Akt) Ser(473) phosphorylation. In contrast, Akt protein and mRNA content were not changed. In summary, although in some aspects cardiac insulin signaling is obviously improved by E2 treatment (increase of p85 mRNA and protein levels, enhancement of IRS-1/p85 association and Ser(473)Akt phosphorylation), the observed decrease of IR tyrosine phosphorylation, IRS-2 protein content, and IRSs mRNA contents, suggest very complex interplay of beneficial and suppressive effects of E2, both genomic and non-genomic, in regulation of heart insulin signaling.

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Low-carbohydrate diet versus euglycemic hyperinsulinemic clamp for the assessment of myocardial viability with 18F-fluorodeoxyglucose-PET: a pilot study

Soares

Filho

Izaki

et al. 2013

Int J Cardiovasc Imaging

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Positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) is considered the gold standard for myocardial viability. A pilot study was undertaken to compare FDG-PET using euglycemic hyperinsulinemic clamp before (18)F-fluorodeoxyglucose ((18)F-FDG) administration (PET-CLAMP) with a new proposed technique consisting of a 24-h low-carbohydrate diet before (18)F-FDG injection (PET-DIET), for the assessment of hypoperfused but viable myocardium (hibernating myocardium). Thirty patients with previous myocardial infarction were subjected to rest (99m)Tc-sestamibi-SPECT and two (18)F-FDG studies (PET-CLAMP and PET-DIET). Myocardial tracer uptake was visually scored using a 5-point scale in a 17-segment model. Hibernating myocardium was defined as normal or mildly reduced metabolism ((18)F-FDG uptake) in areas with reduced perfusion ((99m)Tc-sestamibi uptake) since (18)F-FDG uptake was higher than the degree of hypoperfusion-perfusion/metabolism mismatch indicating a larger flow defect. PET-DIET identified 79 segments and PET-CLAMP 71 as hibernating myocardium. Both methods agreed in 61 segments (agreement = 94.5 %, κ = 0.78). PET-DIET identified 230 segments and PET-CLAMP 238 as nonviable. None of the patients had hypoglycemia after DIET, while 20 % had it during CLAMP. PET-DIET compared with PET-CLAMP had a good correlation for the assessment of hibernating myocardium. To our knowledge, these data provide the first evidence of the possibility of myocardial viability assessment with this technique.

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Influence of insulin and free fatty acids on contractile function in patients with chronically stunned and hibernating myocardium

Cited by 20 publications

References 58 publications

Suppression of circulating free fatty acids with acipimox in chronic heart failure patients changes whole body metabolism but does not affect cardiac function

Suppression of circulating free fatty acids with acipimox in chronic heart failure patients changes whole body metabolism but does not affect cardiac function

Impact of estradiol on insulin signaling in the rat heart

Low-carbohydrate diet versus euglycemic hyperinsulinemic clamp for the assessment of myocardial viability with 18F-fluorodeoxyglucose-PET: a pilot study

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