Protection from Reperfusion Injury with Intracoronary N-Acetylcysteine in Patients with STEMI Undergoing Primary Percutaneous Coronary Intervention in a Cardiac Tertiary Center

Nozari, Younes; Eshraghi, Azadeh; Talasaz, Azita Hajhossein; Bahremand, Mostafa; Salamzadeh, Jamshid; Salarifar, Mojtaba; Pourhosseini, Hamidreza; Jalali, Arash; Mortazavi, Seyedeh Hamideh

doi:10.1007/s40256-017-0258-8

Cited by 16 publications

(15 citation statements)

References 44 publications

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“…NAC was able to reduce the levels of ROS and increase cell survival during ischemia-reperfusion, suggesting that ROS reduction is involved in the protection against ischemia-reperfusion afforded by shifting metabolism towards increased glycolysis. Although the reduction of ROS has been associated with protection against ischemia-reperfusion injury [20] and the administration of high dose NAC to STEMI patients was able to reduce troponin levels and improve coronary blood flow [38], our results are the first evidence linking ROS with the protective mechanism of metabolic shift.…”

Section: Discussionmentioning

confidence: 55%

Enhancing Glycolysis Protects against Ischemia-Reperfusion Injury by Reducing ROS Production

et al. 2020

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After myocardial ischemia-reperfusion, fatty acid oxidation shows fast recovery while glucose oxidation rates remain depressed. A metabolic shift aimed at increasing glucose oxidation has shown to be beneficial in models of myocardial ischemia-reperfusion. However, strategies aimed at increasing glucose consumption in the clinic have provided mixed results and have not yet reached routine clinical practice. A better understanding of the mechanisms underlying the protection afforded by increased glucose oxidation may facilitate the transfer to the clinic. The purpose of this study was to evaluate if the modulation of reactive oxygen species (ROS) was involved in the protection afforded by increased glucose oxidation. Firstly, we characterized an H9C2 cellular model in which the use of glucose or galactose as substrates can modulate glycolysis and oxidative phosphorylation pathways. In this model, there were no differences in morphology, cell number, or ATP and PCr levels. However, galactose-grown cells consumed more oxygen and had an increased Krebs cycle turnover, while cells grown in glucose had increased aerobic glycolysis rate as demonstrated by higher lactate and alanine production. Increased aerobic glycolysis was associated with reduced ROS levels and protected the cells against simulated ischemia-reperfusion injury. Furthermore, ROS scavenger N-acetyl cysteine (NAC) was able to reduce the amount of ROS and to prevent cell death. Lastly, cells grown in galactose showed higher activation of mTOR/Akt signaling pathways. In conclusion, our results provide evidence indicating that metabolic shift towards increased glycolysis reduces mitochondrial ROS production and prevents cell death during ischemia-reperfusion injury.

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Section: Discussionmentioning

confidence: 55%

Enhancing Glycolysis Protects against Ischemia-Reperfusion Injury by Reducing ROS Production

et al. 2020

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“…Nozari et al performed a randomized, double-blind, placebo-controlled trial, wherein they administered NAC before and during reperfusion. This resulted in a significant decrease in hs-TNT levels in patients supplemented with NAC versus the placebo, along with a higher percentage of patients with TIMI 3 flow in those who received the drug [ 105 ]. However, this study did not measure infarct size or other oxidative stress biomarkers.…”

Section: Cardioprotective Effects Exerted By Other Antioxidantsmentioning

confidence: 99%

Joint Cardioprotective Effect of Vitamin C and Other Antioxidants against Reperfusion Injury in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention

et al. 2021

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Percutaneous coronary intervention (PCI) has long remained the gold standard therapy to restore coronary blood flow after acute myocardial infarction (AMI). However, this procedure leads to the development of increased production of reactive oxygen species (ROS) that can exacerbate the damage caused by AMI, particularly during the reperfusion phase. Numerous attempts based on antioxidant treatments, aimed to reduce the oxidative injury of cardiac tissue, have failed in achieving an effective therapy for these patients. Among these studies, results derived from the use of vitamin C (Vit C) have been inconclusive so far, likely due to suboptimal study designs, misinterpretations, and the erroneous conclusions of clinical trials. Nevertheless, recent clinical trials have shown that the intravenous infusion of Vit C prior to PCI-reduced cardiac injury biomarkers, as well as inflammatory biomarkers and ROS production. In addition, improvements of functional parameters, such as left ventricular ejection fraction (LVEF) and telediastolic left ventricular volume, showed a trend but had an inconclusive association with Vit C. Therefore, it seems reasonable that these beneficial effects could be further enhanced by the association with other antioxidant agents. Indeed, the complexity and the multifactorial nature of the mechanism of injury occurring in AMI demands multitarget agents to reach an enhancement of the expected cardioprotection, a paradigm needing to be demonstrated. The present review provides data supporting the view that an intravenous infusion containing combined safe antioxidants could be a suitable strategy to reduce cardiac injury, thus improving the clinical outcome, life quality, and life expectancy of patients subjected to PCI following AMI.

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“…24) NAC is an effective antioxidant, which can directly scavenge hydroxyl free radicals, 25) which can reduce the oxidative damage of target tissues and allow for sufficient oxygen consumption. 26) Nozari, et al 10) found that injecting a high dose of NAC before PCI significantly reduced the hs-TnT level and improved coronary perfusion caused by thrombolysis in myocardial infarction (TIMI) flow after PCI. Pasupathy,et al 11) demonstrated that the infarct size decreased in patients with acute STEMI after PCI when a large dose of NAC was injected intravenously.…”

Section: Discussionmentioning

confidence: 99%

“…Randomization was mentioned in all studies. However, 8 studies [8][9][10][11][12][13]15,16) expounded the generation of random sequences. Only one study 8) described allocation concealment.…”

Section: Basic Information Of the Included Literaturementioning

confidence: 99%

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The Clinical Efficacy of N-Acetylcysteine in the Treatment of ST Segment Elevation Myocardial Infarction

Shu

Cheng-hu

2021

Int. Heart J.

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Protection from Reperfusion Injury with Intracoronary N-Acetylcysteine in Patients with STEMI Undergoing Primary Percutaneous Coronary Intervention in a Cardiac Tertiary Center

Cited by 16 publications

References 44 publications

Enhancing Glycolysis Protects against Ischemia-Reperfusion Injury by Reducing ROS Production

Enhancing Glycolysis Protects against Ischemia-Reperfusion Injury by Reducing ROS Production

Joint Cardioprotective Effect of Vitamin C and Other Antioxidants against Reperfusion Injury in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention

The Clinical Efficacy of N-Acetylcysteine in the Treatment of ST Segment Elevation Myocardial Infarction

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