The role of pyruvate-induced enhancement of oxygen metabolism in extracellular purinergic signaling in the post-cardiac arrest rat model.

Autor: Shinozaki K; The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA. shino@gk9.so-net.ne.jp.; Department of Emergency Medicine, Zucker School of Medicine at Hofstra/Northwell, New York, NY, USA. shino@gk9.so-net.ne.jp.; Department of Emergency Medicine, Kindai University Faculty of Medicine, Osaka, Japan. shino@gk9.so-net.ne.jp., Wong V; The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA., Aoki T; The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA., Hayashida K; The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA., Takegawa R; The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA., Endo Y; The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA., Nandurkar H; Australian Centre for Blood Diseases, Monash University, Melbourne, Australia., Diamond B; The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA., Robson SC; Department of Anesthesia: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Becker LB; The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.; Department of Emergency Medicine, Zucker School of Medicine at Hofstra/Northwell, New York, NY, USA.
Jazyk: angličtina
Zdroj: Purinergic signalling [Purinergic Signal] 2024 Aug; Vol. 20 (4), pp. 345-357. Date of Electronic Publication: 2023 Jul 29.
DOI: 10.1007/s11302-023-09958-7
Abstrakt: Purine nucleotide adenosine triphosphate (ATP) is a source of intracellular energy maintained by mitochondrial oxidative phosphorylation. However, when released from ischemic cells into the extracellular space, they act as death-signaling molecules (eATP). Despite there being potential benefit in using pyruvate to enhance mitochondria by inducing a highly oxidative metabolic state, its association with eATP levels is still poorly understood. Therefore, while we hypothesized that pyruvate could beneficially increase intracellular ATP with the enhancement of mitochondrial function after cardiac arrest (CA), our main focus was whether a proportion of the raised intracellular ATP would detrimentally leak out into the extracellular space. As indicated by the increased levels in systemic oxygen consumption, intravenous administrations of bolus (500 mg/kg) and continuous infusion (1000 mg/kg/h) of pyruvate successfully increased oxygen metabolism in post 10-min CA rats. Plasma ATP levels increased significantly from 67 ± 11 nM before CA to 227 ± 103 nM 2 h after the resuscitation; however, pyruvate administration did not affect post-CA ATP levels. Notably, pyruvate improved post-CA cardiac contraction and acidemia (low pH). We also found that pyruvate increased systemic CO 2 production post-CA. These data support that pyruvate has therapeutic potential for improving CA outcomes by enhancing oxygen and energy metabolism in the brain and heart and attenuating intracellular hydrogen ion disorders, but does not exacerbate the death-signaling of eATP in the blood.
(© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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