Unknown

Dataset Information

0

Stimulation of the Hydroxycarboxylic Acid Receptor 2 With the Ketone Body 3-Hydroxybutyrate and Niacin in Patients With Chronic Heart Failure: Hemodynamic and Metabolic Effects.


ABSTRACT: Background The ketone body 3-hydroxybutyrate (3-OHB) increases cardiac output (CO) in patients with heart failure through unknown mechanisms. 3-OHB activates the hydroxycarboxylic acid receptor 2 (HCA2), which increases prostaglandins and suppresses circulating free fatty acids. We investigated whether the cardiovascular effects of 3-OHB involved HCA2 activation and if the potent HCA2-stimulator niacin may increase CO. Methods and Results Twelve patients with heart failure with reduced ejection fraction were included in a randomized crossover study and examined by right heart catheterization, echocardiography, and blood sampling on 2 separate days. On study day 1, patients received aspirin to block the HCA2 downstream cyclooxygenase enzyme, followed by 3-OHB and placebo infusions in random order. We compared the results with those of a previous study in which patients received no aspirin. On study day 2, patients received niacin and placebo. The primary end point was CO. 3-OHB increased CO (2.3 L/min, P<0.01), stroke volume (19 mL, P<0.01), heart rate (10 bpm, P<0.01), and mixed venous saturation (5%, P<0.01) with preceding aspirin. 3-OHB did not change prostaglandin levels, neither in the ketone/placebo group receiving aspirin nor the previous study cohort. Aspirin did not block 3-OHB-induced changes in CO (P=0.43). 3-OHB decreased free fatty acids by 58% (P=0.01). Niacin increased prostaglandin D2 levels by 330% (P<0.02) and reduced free fatty acids by 75% (P<0.01) but did not affect CO. Conclusions The acute increase in CO during 3-OHB infusion was not modified by aspirin, and niacin had no hemodynamic effects. These findings show that HCA2 receptor-mediated effects were not involved in the hemodynamic response to 3-OHB. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04703361.

SUBMITTER: Gopalasingam N 

PROVIDER: S-EPMC10356045 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Stimulation of the Hydroxycarboxylic Acid Receptor 2 With the Ketone Body 3-Hydroxybutyrate and Niacin in Patients With Chronic Heart Failure: Hemodynamic and Metabolic Effects.

Gopalasingam Nigopan N   Christensen Kristian Hylleberg KH   Berg Hansen Kristoffer K   Nielsen Roni R   Johannsen Mogens M   Gormsen Lars Christian LC   Boedtkjer Ebbe E   Nørregaard Rikke R   Møller Niels N   Wiggers Henrik H  

Journal of the American Heart Association 20230610 12


Background The ketone body 3-hydroxybutyrate (3-OHB) increases cardiac output (CO) in patients with heart failure through unknown mechanisms. 3-OHB activates the hydroxycarboxylic acid receptor 2 (HCA<sub>2</sub>), which increases prostaglandins and suppresses circulating free fatty acids. We investigated whether the cardiovascular effects of 3-OHB involved HCA<sub>2</sub> activation and if the potent HCA<sub>2</sub>-stimulator niacin may increase CO. Methods and Results Twelve patients with hea  ...[more]

Similar Datasets

| S-EPMC6493702 | biostudies-literature
| S-EPMC9203800 | biostudies-literature
| S-EPMC10640643 | biostudies-literature
| S-EPMC8564907 | biostudies-literature
| S-EPMC7955062 | biostudies-literature
| S-EPMC11262493 | biostudies-literature
| S-EPMC10774377 | biostudies-literature
| S-EPMC9208164 | biostudies-literature
| S-EPMC8097358 | biostudies-literature
| S-EPMC6137158 | biostudies-literature