Sodium Nitrite–Mediated Cardioprotection in Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: A Cost-Effectiveness Analysis

Jones, Daniel A.; Whittaker, Peter; Rathod, Krishnaraj S.; Richards, Amy J; Andiapen, Mervyn; Antoniou, Sotiris; Mathur, Anthony; Ahluwalia, Amrita

doi:10.1177/1074248418784940

Cited by 4 publications

(1 citation statement)

References 16 publications

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“…Animal experiments have confirmed the effectiveness of NO donor, such as organic nitrates and nitrites, in alleviating myocardial ischemiareperfusion injury (14,15). These drugs may reduce infarct area and improve cardiomyocyte survival rate by reducing platelet aggregation, alleviating inflammation, and reducing oxidative stress (16)(17)(18)(19)(20). Although many animal experiments have confirmed that nitrite drugs can protect against myocardial ischemia-reperfusion injury, the clinical trial results of these drugs are not ideal, and their efficacy in patients with acute coronary syndrome (ACS) is still uncertain.…”

Section: Introductionmentioning

confidence: 87%

Soluble guanylate cyclase (sGC) stimulator vericiguat alleviates myocardial ischemia-reperfusion injury by improving microcirculation

Cai¹,

Zhang²,

Shalamu³

et al. 2022

Ann Transl Med

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Background: This study aimed to verify the effect of soluble guanylate cyclase (sGC) stimulator vericiguat on myocardial ischemia-reperfusion injury and explore its mechanism.Methods: A myocardial ischemia-reperfusion injury model of mice was established and intravenous administration was performed 2 minutes before reperfusion. Triphenyltetrazolium chloride (TTC) staining and echocardiography were used to verify the effect of vericiguat on myocardial ischemia-reperfusion injury in the infarct area, and immunofluorescence was used to observe myocardial pathological changes at different time points after reperfusion. Quantitative proteomics was conducted to analysis the main differentially expressed proteins after drug intervention. The distribution of endothelial cells and sGC after myocardial ischemia-reperfusion injury in mice was observed by immunofluorescence. RNA sequencing of endothelial cells was used to search for differentially expressed molecules. Thioflavin-S staining was used to observe the effect of vericiguat on improving the nonrecurrence phenomenon and reducing the infarct size after reperfusion.Results: The effect of the sGC stimulator vericiguat on myocardial ischemia-reperfusion injury was verified, and myocardial microcirculation significantly increased after drug intervention. Quantitative proteomics found that the protein expression of myocardial tissue in the ischemia-reperfusion area was not significantly different in the drug intervention group, except for increased adenosine triphosphate (ATP) activity. Vericiguat, nitroglycerin, and nitrite did not directly affect apoptosis or cell viability. RNA sequencing of human umbilical vein endothelial cells screened the upregulated antioxidant response.Conclusions: SGC stimulator vericiguat ameliorated myocardial ischemia-reperfusion injury through indirect pathways of improving microcirculation.

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Section: Introductionmentioning

confidence: 87%

Soluble guanylate cyclase (sGC) stimulator vericiguat alleviates myocardial ischemia-reperfusion injury by improving microcirculation

Cai¹,

Zhang²,

Shalamu³

et al. 2022

Ann Transl Med

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Therapeutic Implications of Nitrite in Hypertension

Ling

Mustafa

Murugan

2020

Journal of Cardiovascular Pharmacology

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Nitrite, an anion produced from the oxidative breakdown of nitric oxide (NO), has traditionally been viewed as an inert molecule. However, this dogma has been challenged with the findings that nitrite can be readily reduced to NO under pathological conditions, hence representing a physiologically relevant storage reservoir of NO either in the blood or tissues. Nitrite administration has been demonstrated to improve myocardial function in subjects with heart failure and to lower the blood pressure in hypertensive subjects. Thus, extensive amount of work has since been carried out to investigate the therapeutic potential of nitrite in treating cardiovascular diseases, especially hypertension. Studies done on several animal models of hypertension have demonstrated the efficacy of nitrite in preventing and ameliorating the pathological changes associated with the disease. This brief review of the current findings aims to re-evaluate the use of nitrite for the treatment of hypertension and in particular to highlight its role in improving endothelial function.

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Effects of Oral Sodium Nitrite on Blood Pressure, Insulin Sensitivity, and Intima-Media Arterial Thickening in Adults With Hypertension and Metabolic Syndrome

et al. 2020

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The nitrate-nitrite-NO pathway regulates NO synthase–independent vasodilation and NO signaling. Ingestion of inorganic nitrite has vasodilatory and blood pressure–lowering effects. Preclinical studies in rodent models suggest there may be a benefit of nitrite in lowering serum triglyceride levels and improving the metabolic syndrome. In a phase 2 study, we evaluated the safety and efficacy of chronic oral nitrite therapy in patients with hypertension and the metabolic syndrome. Twenty adult subjects with stage 1 or 2 hypertension and the metabolic syndrome were enrolled in an open-label safety and efficacy study. The primary efficacy end point was blood pressure reduction; secondary end points included insulin-dependent glucose disposal and endothelial function measured by flow-mediated dilation of the brachial artery and intima-media diameter of the carotid artery. Chronic oral nitrite therapy (40 mg/3× daily) was well tolerated. Oral nitrite significantly lowered systolic, diastolic, and mean arterial pressures, but tolerance was observed after 10 to 12 weeks of therapy. There was significant improvement in the intima-media thickness of the carotid artery and trends toward improvements in flow-mediated dilation of the brachial artery and insulin sensitivity. Chronic oral nitrite therapy is safe in patients with hypertension and the metabolic syndrome. Despite an apparent lack of enzymatic tolerance to nitrite, we observed tolerance after 10 weeks of chronic therapy, which requires additional mechanistic studies and possible therapeutic dose titration in clinical trials. Nitrite may be a safe therapy to concominantly improve multiple features of the metabolic syndrome including hypertension, insulin resistance, and endothelial dysfunction. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01681810.

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Sodium Nitrite–Mediated Cardioprotection in Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: A Cost-Effectiveness Analysis

Abstract: This first analysis of sodium nitrite as a cardioprotective treatment demonstrates cost-effectiveness. Although more comparative analysis and assessment of longer follow-up times are required, our data indicate the considerable potential of nitrite-mediated cardioprotection.

Cited by 4 publications

References 16 publications

Soluble guanylate cyclase (sGC) stimulator vericiguat alleviates myocardial ischemia-reperfusion injury by improving microcirculation

Soluble guanylate cyclase (sGC) stimulator vericiguat alleviates myocardial ischemia-reperfusion injury by improving microcirculation

Therapeutic Implications of Nitrite in Hypertension

Effects of Oral Sodium Nitrite on Blood Pressure, Insulin Sensitivity, and Intima-Media Arterial Thickening in Adults With Hypertension and Metabolic Syndrome

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