Myocardial Free Fatty Acid and Glucose Use After Carvedilol Treatment in Patients With Congestive Heart Failure

Wallhaus, Thomas R.; Taylor, Michael D.; DeGrado, Timothy R.; Russell, Debra; Stanko, Peter; Nickles, Robert J.; Stone, Charles K.

doi:10.1161/01.cir.103.20.2441

Cited by 230 publications

(134 citation statements)

References 42 publications

(33 reference statements)

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“…Beta-blockers reduce heart rate and prolong the diastolic period, thereby decreasing both oxygen consumption of myocardium and increasing oxygen supply to myocardium. Consequently, they can improve myocardial relaxation or diastolic functions and metabolism [15,21].…”

Section: Discussionmentioning

confidence: 99%

Comparison of the effects of carvedilol and nebivolol on diastolic functions of the left ventricle in patients with non-ischemic heart failure

et al. 2014

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Background: We investigated whether carvediolol or nebiovolol with vasodilator properties will produce different effects on diastolic function of the left ventricle (LV) in heart failure (HF) with low ejection fraction (EF).Methods: Sixty-one non-ischemic HF patients with EF £ 40% randomly received carvedilol (n = 31, 16 male) or nebivolol (n = 30, 19 DT prolonged (from 184 ± 40 to 218 ± 42 ms vs. from 193 ± 37 to 222 ± 36 ms, p = 0.71). Also, E/Ea ratio significantly decreased in each group (p = 0.01), but it was lower in nebivolol group than carvedilol group at 6 months (10.2 ± 2 vs. 11.8 ± 2, p = 0.41, respectively) and improved functional capacity (p > 0.05). Conclusions: At 6 month follow-up, carvedilol and nebivolol appear to similarly improve LV diastolic functions in non-ischemic HF patients. (Cardiol J 2014; 21, 1: 76-82) male). Clinical and echocardiographic evaluations were performed at baseline, 3 and 6 months after therapy. Mitral inflow velocities (E and A waves), deceleration time of E wave (DT), isovolumetric relaxation time (IVRT), mitral annular velocities (Ea and Aa waves) were evaluated. Mitral E/A and E/Ea ratios were calculated. Results: In carvediolol and nebivolol groups, mitral E/

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Section: Discussionmentioning

confidence: 99%

Comparison of the effects of carvedilol and nebivolol on diastolic functions of the left ventricle in patients with non-ischemic heart failure

et al. 2014

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“…Over the last 20 y, our laboratory has investigated radiolabeled thia-substituted long-chain fatty acid analogs as metabolically trapped probes of myocardial FAO (12)(13)(14)(15)(16)(17). The first-generation molecule 14-18 F-fluoro-6-thiaheptadecanoic acid ( 18 F-FTHA) was a 6-thia analog that showed excellent myocardial imaging properties but lacked specificity for mitochondrial FAO in certain conditions such as oxygen insufficiency (14,15).…”

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confidence: 99%

Synthesis and Preliminary Evaluation of 18-¹⁸F-Fluoro-4-Thia-Oleate as a PET Probe of Fatty Acid Oxidation

DeGrado

Bhattacharyya

Pandey³

et al. 2010

J Nucl Med

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Fatty acid oxidation (FAO) is a major energy-providing process with important implications in cardiovascular, oncologic, neurologic, and metabolic diseases. A novel 4-thia oleate analog, 18-18 F-fluoro-4-thia-oleate ( 18 F-FTO), was evaluated in relationship to the previously developed palmitate analog 16-18 Ffluoro-4-thia-palmitate ( 18 F-FTP) as an FAO probe. Methods: 18 F-FTO was synthesized from a corresponding bromoester. Biodistribution and metabolite analysis studies were performed in rats. Preliminary small-animal PET studies were performed with 18 F-FTO and 18 F-FTP in rats. Results: A practical synthesis of 18 F-FTO was developed, providing a radiotracer of high radiochemical purity (.99%). In fasted rats, myocardial uptake of 18 F-FTO (0.70 6 0.30% dose kg [body mass]/g [tissue mass]) was similar to that of 18 F-FTP at 30 min after injection. At 2 h, myocardial uptake of 18 F-FTO was maintained, whereas 18 F-FTP uptake in the heart was 82% reduced. Similar to 18 F-FTP, 18 F-FTO uptake by the heart was approximately 80% reduced at 30 min by pretreatment of rats with the CPT-I inhibitor etomoxir. Folch-type extraction analyses showed 70-90% protein-bound fractions in the heart, liver, and skeletal muscle, consistent with efficient trafficking of 18 F-FTO to the mitochondrion with subsequent metabolism to protein-bound species. Preliminary small-animal PET studies showed rapid blood clearance and avid extraction of 18 F-FTO and of 18 F-FTP into the heart and liver. Images of 18 F-FTO accumulation in the rat myocardium were clearly superior to those of 18 F-FTP. Conclusion: 18 F-FTO is shown to be a promising metabolically trapped FAO probe that warrants further evaluation.

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“…Insulin appears to suppress the secretion and antagonize the harmful effects of TNF-α, macrophage migration inhibitory factor, and superoxide anion (28)(29)(30) and increase anti-inflammatory signal transduction (31)(32)(33). Furthermore, insulin has been found to suppress free fatty acids and increase the utilization of glucose, providing an efficient energy source (34,35). Due to the anti-inflammatory and metabolic effects of insulin, in combination with providing glucose to the myocardium, GIK appears to be a useful approach in septic shock patients with myocardial depression.…”

Section: Discussionmentioning

confidence: 99%

Glucose-insulin-potassium correlates with hemodynamic improvement in patients with septic myocardial dysfunction

et al. 2016

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Myocardial Free Fatty Acid and Glucose Use After Carvedilol Treatment in Patients With Congestive Heart Failure

Abstract: Carvedilol treatment in patients with heart failure results in a 57% decrease in myocardial FFA use without a significant change in glucose use. These metabolic changes could contribute to the observed improvements in energy efficiency seen in patients with heart failure.

Cited by 230 publications

References 42 publications

Comparison of the effects of carvedilol and nebivolol on diastolic functions of the left ventricle in patients with non-ischemic heart failure

Comparison of the effects of carvedilol and nebivolol on diastolic functions of the left ventricle in patients with non-ischemic heart failure

Synthesis and Preliminary Evaluation of 18-¹⁸F-Fluoro-4-Thia-Oleate as a PET Probe of Fatty Acid Oxidation

Glucose-insulin-potassium correlates with hemodynamic improvement in patients with septic myocardial dysfunction

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Myocardial Free Fatty Acid and Glucose Use After Carvedilol Treatment in Patients With Congestive Heart Failure

Abstract: Carvedilol treatment in patients with heart failure results in a 57% decrease in myocardial FFA use without a significant change in glucose use. These metabolic changes could contribute to the observed improvements in energy efficiency seen in patients with heart failure.

Cited by 230 publications

References 42 publications

Comparison of the effects of carvedilol and nebivolol on diastolic functions of the left ventricle in patients with non-ischemic heart failure

Comparison of the effects of carvedilol and nebivolol on diastolic functions of the left ventricle in patients with non-ischemic heart failure

Synthesis and Preliminary Evaluation of 18-18F-Fluoro-4-Thia-Oleate as a PET Probe of Fatty Acid Oxidation

Glucose-insulin-potassium correlates with hemodynamic improvement in patients with septic myocardial dysfunction

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Synthesis and Preliminary Evaluation of 18-¹⁸F-Fluoro-4-Thia-Oleate as a PET Probe of Fatty Acid Oxidation