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Nicotinamide restores tissue NAD(+) and improves survival in rodent models of cardiac arrest
Metabolic suppression in the ischemic heart is characterized by reduced levels of NAD(+) and ATP. Since NAD(+) is required for most metabolic processes that generate ATP, we hypothesized that nicotinamide restores ischemic tissue NAD(+) and improves cardiac function in cardiomyocytes and isolated he...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10503771/ https://www.ncbi.nlm.nih.gov/pubmed/37713442 http://dx.doi.org/10.1371/journal.pone.0291598 |
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author | Zhu, Xiangdong Li, Jing Wang, Huashan Gasior, Filip M. Lee, Chunpei Lin, Shaoxia Justice, Cody N. O’Donnell, J. Michael Vanden Hoek, Terry L. |
author_facet | Zhu, Xiangdong Li, Jing Wang, Huashan Gasior, Filip M. Lee, Chunpei Lin, Shaoxia Justice, Cody N. O’Donnell, J. Michael Vanden Hoek, Terry L. |
author_sort | Zhu, Xiangdong |
collection | PubMed |
description | Metabolic suppression in the ischemic heart is characterized by reduced levels of NAD(+) and ATP. Since NAD(+) is required for most metabolic processes that generate ATP, we hypothesized that nicotinamide restores ischemic tissue NAD(+) and improves cardiac function in cardiomyocytes and isolated hearts, and enhances survival in a mouse model of cardiac arrest. Mouse cardiomyocytes were exposed to 30 min simulated ischemia and 90 min reperfusion. NAD(+) content dropped 40% by the end of ischemia compared to pre-ischemia. Treatment with 100 μM nicotinamide (NAM) at the start of reperfusion completely restored the cellular level of NAD(+) at 15 min of reperfusion. This rescue of NAD(+) depletion was associated with improved contractile recovery as early as 10 min post-reperfusion. In a mouse model of cardiac arrest, 100 mg/kg NAM administered IV immediately after cardiopulmonary resuscitation resulted in 100% survival at 4 h as compared to 50% in the saline group. In an isolated rat heart model, the effect of NAM on cardiac function was measured for 20 min following 18 min global ischemia. Rate pressure product was reduced by 26% in the control group following arrest. Cardiac contractile function was completely recovered with NAM treatment given at the start of reperfusion. NAM restored tissue NAD(+) and enhanced production of lactate and ATP, while reducing glucose diversion to sorbitol in the heart. We conclude that NAM can rapidly restore cardiac NAD(+) following ischemia and enhance glycolysis and contractile recovery, with improved survival in a mouse model of cardiac arrest. |
format | Online Article Text |
id | pubmed-10503771 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-105037712023-09-16 Nicotinamide restores tissue NAD(+) and improves survival in rodent models of cardiac arrest Zhu, Xiangdong Li, Jing Wang, Huashan Gasior, Filip M. Lee, Chunpei Lin, Shaoxia Justice, Cody N. O’Donnell, J. Michael Vanden Hoek, Terry L. PLoS One Research Article Metabolic suppression in the ischemic heart is characterized by reduced levels of NAD(+) and ATP. Since NAD(+) is required for most metabolic processes that generate ATP, we hypothesized that nicotinamide restores ischemic tissue NAD(+) and improves cardiac function in cardiomyocytes and isolated hearts, and enhances survival in a mouse model of cardiac arrest. Mouse cardiomyocytes were exposed to 30 min simulated ischemia and 90 min reperfusion. NAD(+) content dropped 40% by the end of ischemia compared to pre-ischemia. Treatment with 100 μM nicotinamide (NAM) at the start of reperfusion completely restored the cellular level of NAD(+) at 15 min of reperfusion. This rescue of NAD(+) depletion was associated with improved contractile recovery as early as 10 min post-reperfusion. In a mouse model of cardiac arrest, 100 mg/kg NAM administered IV immediately after cardiopulmonary resuscitation resulted in 100% survival at 4 h as compared to 50% in the saline group. In an isolated rat heart model, the effect of NAM on cardiac function was measured for 20 min following 18 min global ischemia. Rate pressure product was reduced by 26% in the control group following arrest. Cardiac contractile function was completely recovered with NAM treatment given at the start of reperfusion. NAM restored tissue NAD(+) and enhanced production of lactate and ATP, while reducing glucose diversion to sorbitol in the heart. We conclude that NAM can rapidly restore cardiac NAD(+) following ischemia and enhance glycolysis and contractile recovery, with improved survival in a mouse model of cardiac arrest. Public Library of Science 2023-09-15 /pmc/articles/PMC10503771/ /pubmed/37713442 http://dx.doi.org/10.1371/journal.pone.0291598 Text en © 2023 Zhu et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Zhu, Xiangdong Li, Jing Wang, Huashan Gasior, Filip M. Lee, Chunpei Lin, Shaoxia Justice, Cody N. O’Donnell, J. Michael Vanden Hoek, Terry L. Nicotinamide restores tissue NAD(+) and improves survival in rodent models of cardiac arrest |
title | Nicotinamide restores tissue NAD(+) and improves survival in rodent models of cardiac arrest |
title_full | Nicotinamide restores tissue NAD(+) and improves survival in rodent models of cardiac arrest |
title_fullStr | Nicotinamide restores tissue NAD(+) and improves survival in rodent models of cardiac arrest |
title_full_unstemmed | Nicotinamide restores tissue NAD(+) and improves survival in rodent models of cardiac arrest |
title_short | Nicotinamide restores tissue NAD(+) and improves survival in rodent models of cardiac arrest |
title_sort | nicotinamide restores tissue nad(+) and improves survival in rodent models of cardiac arrest |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10503771/ https://www.ncbi.nlm.nih.gov/pubmed/37713442 http://dx.doi.org/10.1371/journal.pone.0291598 |
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