sodium-nitrite and Myocardial-Ischemia

The aim of this study was to assess the potential benefits of inorganic nitrite in 2 clinical models: stress-induced myocardial ischemia and whole-arm ischemia-reperfusion.. Inorganic nitrite, traditionally considered a relatively inert metabolite of nitric oxide, may exert vasomodulatory and vasoprotective effects. Despite promising results from animal models, few have shown effectiveness in human model systems, and none have fully translated to the clinical setting.. In 10 patients with inducible myocardial ischemia, saline and low-dose sodium nitrite (NaNO₂) (1.5 μmol/min for 20 min) were administered in a double-blind fashion during dobutamine stress echocardiography, at separate visits and in a random order; long-axis myocardial function was quantified by peak systolic velocity (Vs) and strain rate (SR) responses. In 19 healthy subjects, flow-mediated dilation was assessed before and after whole-arm ischemia-reperfusion; nitrite was given before ischemia or during reperfusion.. Comparing saline and nitrite infusions, Vs and SR at peak dobutamine increased in regions exhibiting ischemia (Vs from 9.5 ± 0.5 cm/s to 12.4 ± 0.6 cm/s, SR from -2.0 ± 0.2 s(-1) to -2.8 ± 0.3 s(-1)), whereas they did not change in normally functioning regions (Vs from 12.6 ± 0.4 cm/s to 12.6 ± 0.6 cm/s, SR from -2.6 ± 0.3 s(-1) to -2.3 ± 0.1 s(-1)) (p < 0.001, analysis of variance). With NaNO2, the increment of Vs (normalized for increase in heart rate) increased only in poorly functioning myocardial regions (+122%, p < 0.001). Peak flow-mediated dilation decreased by 43% after ischemia-reperfusion when subjects received only saline (6.8 ± 0.7% vs. 3.9 ± 0.7%, p < 0.01); administration of NaNO2 before ischemia prevented this decrease in flow-mediated dilation (5.9 ± 0.7% vs. 5.2 ± 0.5%, p = NS), whereas administration during reperfusion did not.. Low-dose NaNO₂ improves functional responses in ischemic myocardium but has no effect on normal regions. Low-dose NaNO₂ protects against vascular ischemia-reperfusion injury only when it is given before the onset of ischemia.

Topics: Adult; Aged; Cardiotonic Agents; Double-Blind Method; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Ischemia; Myocardial Reperfusion Injury; Sodium Nitrite; Young Adult

Sodium nitrite is used as a coloring agent or preservative in food, as well as an antimicrobial agent in meat and fish and some cheeses. In high amounts it can be toxic for humans, causing methemoglobinemia. This is an unusual and potentially fatal condition in which hemoglobin is oxidized to methemoglobin (MHb), reducing the amount of oxygen that is released from hemoglobin, similar to carbon monoxide poisoning. MHb levels of 70% are generally lethal, but the existence of underlying anemia, acidosis, respiratory compromise, and cardiac disease may exacerbate the toxicity of MHb. We present a case of poisoning with sodium nitrite in three family members after eating homemade sausages given to them by their neighbor who was a butcher. According to the findings of the veterinary inspectorate in charge of food control in this case, the concentration of sodium nitrite in the homemade sausages was about 3.5 g per 1 kg of meat, almost 30 times higher than allowed according to legislation. In this case report, a 70-year-old man died about 7 h after consuming the meal, while two women, 53 and 67 years of age, respectively, were admitted to a toxicology clinic the following day due to food poisoning, with the maximum concentration of MHb in blood of 33.7 and 20.4%, respectively. They were discharged 3 days later. The autopsy of the deceased man showed sodium nitrite poisoning with a relatively low concentration of MHb in his blood - 9.87%. Death was attributed to the exacerbation of hypertensive and ischemic heart disease, resulting from accidental sodium nitrite poisoning. The presented cases illustrate the necessity of close cooperation between the authorities, medical staff, veterinary inspectorate, and forensic pathologists in determining the source of poisoning, the cause of death of the victim, and preventing the outbreak of poisoning among a greater number of consumers.

Topics: Accidents, Home; Aged; Female; Food Preservatives; Foodborne Diseases; Humans; Hypertension; Male; Meat Products; Methemoglobinemia; Middle Aged; Myocardial Ischemia; Sodium Nitrite

Ventricular arrhythmias induced by ischemic heart disease are the main cause of sudden cardiac death. Ischemia can cause life-threatening arrhythmias by modulating connexin 43 (Cx43), a principal cardiac gap junction channel protein. The present study investigates whether nitrite can attenuate ischemia-induced ventricular arrhythmias and dephosphorylation of Cx43 in a rat model.. Rats were medicated with normal saline (control, n = 10), nitrite (0.015, 0.15, and 1.5 mg/kg, n = 9 or 10 each), and 0.15 mg/kg nitrite with either the nitric oxide scavenger 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide, sodium salt (cPTIO; n = 9) or allopurinol (xanthine oxidoreductase inhibitor, n = 9). We determined the severity of ventricular arrhythmias based on arrhythmia scores and levels of phosphorylated Cx43.. The median arrhythmia score may have been lower in the group given 0.15 mg/kg nitrite (4 [interquartile range {IQR}, 4-5]) than that in the control group (7.5 [IQR, 5.25-8]; P = 0.013). There was no difference among the control, the given 0.015 mg/kg nitrite (7 [IQR, 5-8]), and 1.5 mg/kg nitrite (7 [IQR, 5.5-7.75]; P = 0.95). The arrhythmia scores in the cPTIO (6 [IQR, 5-8]; P = 0.030) and allopurinol (7 [IQR, 5-8]; P = 0.005) groups may have been higher than that in 0.15 mg/kg nitrite group. Immunoblotting revealed that the level of phosphorylated Cx43 in the group given 0.15 mg/kg nitrite, but not in the other treated groups, was significantly higher compared with the control group (P = 0.007).. Nitrite may have attenuated acute ischemia-induced ventricular arrhythmias and Cx43 dephosphorylation in rats. Nitric oxide, which might be generated by xanthine oxidoreductase via nitrite reduction, appears to play a crucial role in this antiarrhythmic effect.

Topics: Allopurinol; Animals; Arrhythmias, Cardiac; Blood Gas Analysis; Connexin 43; Cyclic N-Oxides; Dose-Response Relationship, Drug; Enzyme Inhibitors; Free Radical Scavengers; Hemodynamics; Imidazoles; Male; Myocardial Ischemia; Nitric Oxide; Phosphorylation; Rats; Rats, Wistar; Sodium Nitrite; Ventricular Dysfunction

Bioavailability of nitric oxide (NO) and hydrogen sulfide (H2S) is reduced in heart failure (HF). Recent studies suggest cross-talk between NO and H2S signaling. We previously reported that sodium nitrite (NaNO2) ameliorates myocardial ischemia-reperfusion injury and HF. Nuclear factor-erythroid-2-related factor 2 (Nrf2) regulates the antioxidant proteins expression and is upregulated by H2S. We examined the NaNO2 effects on endogenous H2S bioavailability and Nrf2 activation in mice subjected to ischemia-induced chronic heart failure (CHF).. Mice underwent 60 minutes of left coronary artery occlusion and 4 weeks of reperfusion. NaNO2 (165 μg/kgic) or vehicle was administered at reperfusion and then in drinking water (100 mg/L) for 4 weeks. Left ventricular (LV), ejection fraction (EF), LV end diastolic (LVEDD) and systolic dimensions (LVESD) were determined at baseline and at 4 weeks of reperfusion. Myocardial tissue was analyzed for oxidative stress and respective gene/protein-related assays. We found that NaNO2 therapy preserved LVEF, LVEDD and LVSD at 4 weeks during ischemia-induced HF. Myocardial malondialdehyde and protein carbonyl content were significantly reduced in NaNO2-treated mice as compared to vehicle, suggesting a reduction in oxidative stress. NaNO2 therapy markedly increased expression of Cu,Zn-superoxide dismutase, catalase, and glutathione peroxidase during 4 weeks of reperfusion. Furthermore, NaNO2 upregulated the activity of Nrf2, as well as H2S-producing enzymes, and ultimately increased H2S bioavailability in ischemia-induced CHF in mice as compared with vehicle.. Our results demonstrate that NaNO2 therapy significantly improves LV function via increasing H2S bioavailability, Nrf2 activation, and antioxidant defenses.

Topics: Animals; Antioxidants; Cardiotonic Agents; Coronary Occlusion; Heart Failure; Hydrogen Sulfide; Male; Mice; Mice, Inbred C57BL; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; NF-E2-Related Factor 2; Nitric Oxide Synthase Type III; Oxidative Stress; Signal Transduction; Sodium Nitrite; Stroke Volume

To provide evidence for the protective role of inorganic nitrite against acute ischaemia and reperfusion-induced ventricular arrhythmias in a large animal model.. Dogs, anaesthetized with chloralose and urethane, were administered intravenously with sodium nitrite (0.2 µmol kg(-1) min(-1)) in two protocols. In protocol 1 nitrite was infused 10 min prior to and during a 25 min occlusion of the left anterior descending (LAD) coronary artery (NaNO2-PO; n = 14), whereas in protocol 2 the infusion was started 10 min prior to reperfusion of the occluded vessel (NaNO2-PR; n = 12). Control dogs (n = 15) were infused with saline and subjected to the same period of ischaemia and reperfusion. Severities of ischaemia and ventricular arrhythmias, as well as changes in plasma nitrate/nitrite (NOx) levels in the coronary sinus blood, were assessed throughout the experiment. Myocardial superoxide and nitrotyrosine (NT) levels were determined during reperfusion. Changes in protein S-nitrosylation (SNO) and S-glutathionylation were also examined.. Compared with controls, sodium nitrite administered either pre-occlusion or pre-reperfusion markedly suppressed the number and severity of ventricular arrhythmias during occlusion and increased survival (0% vs. 50 and 92%) upon reperfusion. There were also significant decreases in superoxide and NT levels in the nitrite treated dogs. Compared with controls, increased SNO was found only in NaNO2-PR dogs, whereas S-glutathionylation occurred primarily in NaNO2-PO dogs.. Intravenous infusion of nitrite profoundly reduced the severity of ventricular arrhythmias resulting from acute ischaemia and reperfusion in anaesthetized dogs. This effect, among several others, may result from an NO-mediated reduction in oxidative stress, perhaps through protein SNO and/or S-glutathionylation.

Topics: Administration, Intravenous; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Disease Models, Animal; Dogs; Hemodynamics; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Nitrates; Nitric Oxide; Nitrites; Protein Processing, Post-Translational; Sodium Nitrite; Superoxides; Tyrosine

To investigate the protective effect of Ginsenoside Rg2 on Chemical myocardial ischemia.. The models of myocardial ischemia were built in rats with isoproterenol, sodium nitrite,pituitrin. Ginsenoside Rg2 (iv 2.5, 5.0, 10.0 mg x kg(-1)) were intravenously administered.. Ginsenoside Rg2 could improve the abnormal electrocardiogram (ECG), reduce the arca of myocardial ischemia and improve the abnormal zymologic value of myocardial.. Ginsenoside Rg2 has inhibitory function on myocardialischemia.

Topics: Animals; Creatine Kinase; Electrocardiography; Female; Ginsenosides; Isoproterenol; Male; Malondialdehyde; Myocardial Ischemia; Myocardium; Panax; Pituitary Hormones, Posterior; Plant Leaves; Plants, Medicinal; Rats; Rats, Wistar; Sodium Nitrite; Superoxide Dismutase

Endothelium-dependent relaxation of the aorta was assessed in JCR:LA-corpulent rats, which are hyperphagous, hyperlipidemic, hyperinsulinemic, and obese and spontaneously develop atherosclerotic disease and myocardial lesions. The findings in corpulent rats (6 months of age) were compared with those in age-and sex-matched lean rats. Aortic rings were prepared and mounted in Krebs-Henseleit buffer in a conventional organ bath. The tissue was contracted with norepinephrine (10(-6) mol/L), and relaxation was induced using acetylcholine, the calcium ionophore A23187, or bradykinin. The maximum relaxation to acetylcholine was impaired in corpulent male rats compared with lean rats, whereas relaxation in response to the calcium ionophore was similar in the corpulent and lean animals. Aortic rings from corpulent and lean female rats showed no differences in response to acetylcholine or to the calcium ionophore. Removal of endothelium resulted in the loss of relaxant response to acetylcholine and the calcium ionophore. The relaxant responses to sodium nitrite were not significantly different in the corpulent and lean male rats when deendothelialized tissues were examined, but the sensitivity to sodium nitrite was significantly lower in rings from corpulent male rats with intact endothelium. There were no differences in the response to bradykinin between corpulent and lean rats. These findings suggest that there is a specific impairment of endothelium-dependent relaxation in the corpulent male rat that is limited to that mediated by muscarinic receptors. The possibility that endothelium-derived contractile agents are secreted in the vessels of corpulent male rats cannot be excluded.

Topics: Animals; Aorta; Arteriosclerosis; Bradykinin; Endothelium, Vascular; Female; Male; Microscopy, Electron, Scanning; Myocardial Ischemia; Rats; Sodium Nitrite; Vasodilation