Nicotinamide restores tissue NAD+ and improves survival in rodent models of cardiac arrest.
Nicotinamide restores tissue NAD+ and improves survival in rodent models of cardiac arrest.
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DOI：
10.1371/journal.pone.0291598
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
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.
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影响因子：
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作者：
Correa, Francisco;Garcia, Noemi;Zazueta, Cecilia
通讯作者：
Zazueta, Cecilia
影响因子：
2.5
作者：
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通讯作者：
Weiss, M
影响因子：
5
作者：
Nadtochiy SM;Wang YT;Nehrke K;Munger J;Brookes PS
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Brookes PS
脂质乳液迅速恢复了惊人的小鼠心肌细胞的收缩力：与治疗性低温的比较。
影响因子：
8.8
作者：
Li J;Fettiplace M;Chen SJ;Steinhorn B;Shao Z;Zhu X;Li C;Harty S;Weinberg G;Vanden Hoek TL
通讯作者：
Vanden Hoek TL
影响因子：
7.3
作者：
Grolla AA;Travelli C;Genazzani AA;Sethi JK
通讯作者：
Sethi JK