ascorbic-acid and Arrhythmias--Cardiac

Topics: Adolescent; Arrhythmias, Cardiac; Ascorbic Acid; Blood Transfusion; Child; Cholelithiasis; Deferoxamine; Endocrine System Diseases; Female; Folic Acid; Growth Disorders; Heart Failure; Hematopoiesis; Humans; Iron; Leg Ulcer; Liver Diseases; Male; Pericarditis; Splenectomy; Thalassemia; Vitamin E

To evaluate the effect of high-dose vitamin C on cardiac reperfusion injury and plasma levels of creatine kinase-muscle/brain (CK-MB), troponin I, and lactate dehydrogenase (LDH) in patients undergoing coronary artery bypass grafting (CABG).. This is a double-blind randomized clinical trial study. Fifty patients (50-80 years old) who had CABG surgery were selected. The intervention group received 5 g of intravenous vitamin C before anesthesia induction and 5 g of vitamin C in cardioplegic solution. The control group received the same amount of placebo (normal saline). Arterial blood samples were taken to determine the serum levels of CK-MB, troponin I, and LDH enzymes. Left ventricular ejection fraction was measured and hemodynamic parameters were recorded at intervals.. High doses of vitamin C in the treatment group led to improvement of ventricular function (ejection fraction [EF]) and low Intensive Care Unit (ICU) stay. The cardiac enzymes level in the vitamin C group was lower than in the control group. These changes were not significant between the groups in different time intervals (anesthesia induction, end of bypass, 6 h after surgery, and 24 h after surgery) for CK-MB, LDH, and troponin I. Hemodynamic parameters, hematocrit, potassium, urinary output, blood transfusion, arrhythmia, and inotropic support showed no significant difference between the groups.. Vitamin C has significantly improved the patients' ventricular function (EF) 72 h after surgery and reduced the length of ICU stay. No significant changes in cardiac biomarkers, including CK-MB, troponin I, and LDH, were seen over time in each group.. IRCT2016053019470N33.

Topics: Aged; Aged, 80 and over; Antioxidants; Arrhythmias, Cardiac; Ascorbic Acid; Biomarkers; Coronary Artery Bypass; Creatine Kinase, BB Form; Creatine Kinase, MM Form; Double-Blind Method; Female; Hemodynamics; Humans; Intensive Care Units; L-Lactate Dehydrogenase; Male; Middle Aged; Myocardial Reperfusion Injury; Reproducibility of Results; Statistics, Nonparametric; Time Factors; Treatment Outcome; Troponin I; Ventricular Function

There is increasing evidence that free radical scavengers limit reperfusion injury in animal experiments. We randomly administered 250 ml 20% mannitol infusion and 10.0 g ascorbic acid infusion, potent free radical scavengers to 42 patients with acute myocardial infarction receiving streptokinase. A control group of 42 patients received only standard fibrinolytic therapy. We found that additional antioxidant treatment with ascorbic acid and mannitol decreased the number of some complications of acute myocardial infarction.

Topics: Arrhythmias, Cardiac; Ascorbic Acid; Female; Follow-Up Studies; Free Radical Scavengers; Humans; Male; Mannitol; Middle Aged; Myocardial Infarction; Myocardial Reperfusion Injury; Streptokinase; Thrombolytic Therapy; Time Factors

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Ascorbic Acid; Clinical Trials as Topic; Disopyramide; Drug Combinations; Female; Humans; Male; Middle Aged; Rutin

The purpose of this study is to determine if antioxidant supplementation influences the incidence of atrial arrhythmias in trauma intensive care unit (ICU) patients.. In this retrospective pre-post study, critically ill injured patients aged ≥18 years, admitted to a single-center trauma ICU for ≥48 hours were eligible for inclusion. The control group consists of patients admitted from January 2000 to September 2005, before routine antioxidant supplementation in our ICU. The antioxidant group consists of patients admitted from October 2005 to June 2011 who received an antioxidant protocol for ≥48 hours. The primary outcome is the incidence of atrial arrhythmias in the first 2 weeks of hospitalization or before discharge.. Of the 4699 patients, 1622 patients were in the antioxidant group and 2414 patients were in the control group. Adjusted for age, sex, year, injury severity, past medical history, and medication administration, the unadjusted incidence of atrial arrhythmias was 3.02% in the antioxidant group versus 3.31% in the control group, with no adjusted difference in atrial arrhythmias among those exposed to antioxidants (odds ratio: 1.31 [95% confidence interval: 0.46, 3.75], P = 0.62). Although there was no change in overall mortality, the expected adjusted survival of patients in those without antioxidant therapy was lower (odds ratio: 0.65 [95% confidence interval: 0.43, 0.97], P = 0.04).. ICU antioxidant supplementation did not decrease the incidence of atrial arrhythmias, nor alter the time from admission to development of arrhythmia. A longer expected survival time was observed in the antioxidant group compared with the control group but without a change in overall mortality between groups.

Topics: Adult; Antioxidants; Arrhythmias, Cardiac; Ascorbic Acid; Critical Care; Critical Illness; Dietary Supplements; Female; Humans; Male; Middle Aged; Oxidative Stress; Retrospective Studies; Selenium; Trauma Centers; Vitamin D; Wounds and Injuries

We have studied the role of oxidant stress in development of rhythm disturbances in early postoperative period after coronary artery bypass grafting and possibilities of their prevention with preparations of ascorbinic acid. It was shown that the use of β-adrenoblockers allows to prevent arrhythmia on first day after operation only in 80% of cases. Patients with developed disturbances of cardiac rhythm were characterized by high parameters of lipid peroxidation (LPO) and substantial changes of activity of antioxidant enzyme catalase. Administration of ascorbinic acid at the stage of preparation of patients to surgery and in first 24 hours after operation allowed to effectively prevent development of oxidative stress and disturbances of cardiac rhythm. A conclusion was made that inclusion of ascorbinic acid in drug therapy of patients with ischemic heart disease could be recommended for prevention of arrhythmia in postoperative period.

Topics: Aged; Antioxidants; Arrhythmias, Cardiac; Ascorbic Acid; Coronary Artery Bypass; Drug Monitoring; Humans; Male; Middle Aged; Myocardial Ischemia; Oxidative Stress; Postoperative Care; Postoperative Complications; Time Factors; Treatment Outcome

Since excessive amounts of catecholamines are known to produce arrhythmias and increase the plasma level of aminochrome, an oxidation product of catecholamines, we tested the hypothesis that antioxidants may reduce the formation of aminochrome and prevent the catecholamine-induced arrhythmias. For this purpose, Sprague-Dawley rats were pretreated orally, with vitamin A or vitamin C for 21 days, and their effects on ventricular arrhythmias induced by a bolus dose or cumulative doses of intravenous epinephrine were examined. Electrocardiogram recording of these animals revealed that pretreatment with either of these vitamins increased the time of onset and decreased the duration of the epinephrine-induced ventricular arrhythmias. Ventricular fibrillations due to high doses of epinephrine were also prevented by the antioxidant pretreatment. Although pretreatment with either vitamin A or vitamin C did not affect the basal malondialdehyde level in control animals, the increase in malondialdehyde level caused by epinephrine administration was significantly reduced by these agents. The elevated level of plasma aminochrome due to epinephrine was also decreased by vitamins A and C treatments. The results indicate that antioxidant may prevent catecholamine-induced arrhythmias by reducing the formation of aminochrome and thus may provide a new strategy for the management of stress-related heart disease.

Topics: Animals; Anti-Arrhythmia Agents; Antioxidants; Arrhythmias, Cardiac; Ascorbic Acid; Dose-Response Relationship, Drug; Epinephrine; Free Radical Scavengers; Male; Rats; Rats, Sprague-Dawley; Vitamin A; Vitamins

Vitamin C is considered to be a very efficient water-soluble antioxidant, for which several new cardiovascular properties were recently described. The aim of this study was to determine in vivo the effects of a severe depletion of vitamin C on cardiac and vascular variables and reperfusion arrhythmias. For this purpose, we used a mutant strain of Wistar rats, osteogenic disorder Shionogi (ODS). After 15 d of consuming a vitamin C-deficient diet, ODS rats had a 90% decrease in plasma and tissue levels of ascorbate compared with ODS vitamin C-supplemented rats and normal Wistar rats. However, plasma antioxidant capacity, proteins, alpha-tocopherol, urate, catecholamines, lipids, and nitrate were not influenced by the vitamin C deficiency in ODS rats. Moreover, there was no difference between ODS vitamin C-deficient and -supplemented rats in heart rate and arterial pressure. After 5 min of an in vivo regional myocardial ischemia, various severe arrhythmias were observed, but their intensities were not modified by vitamin C in vitamin C-deficient ODS rats. The vascular reactivity, measured in vitro on thoracic arteries, was not altered by ascorbate deficiency in ODS rats. These unexpected results suggest that unidentified compensatory mechanisms play a role in maintaining normal cardiac function and vascular reactivity in vitamin C-deficient rats.

Topics: Acetylcholine; alpha-Tocopherol; Animals; Aorta; Arrhythmias, Cardiac; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Pressure; Bone Diseases; Cardiovascular Diseases; Diet; Epinephrine; Heart Rate; Male; Muscle Contraction; Myocardial Ischemia; Myocardial Reperfusion; Norepinephrine; Osteogenesis; Phenylephrine; Rats; Rats, Mutant Strains; Rats, Wistar

We propose a method for experimental modeling of cardiac arrhythmias. The method consists in intravenous injection of LPO inductors: 5% ascorbic acid (50 mg/kg), 1 min later 1% iron sulfate (10 mg/kg), and after the appearance of giant T waves on ECG infusion of 10% calcium chloride in a nonarrhythmogenic dose 100 mg/kg. Cardiac arrhythmias were induced in 100% animals. A significant relationship between increased permeability of erythrocyte membranes and development of fatal cardiac arrhythmias was detected. We assumed that this methodologically simple membrane-destructive model of cardiac arrhythmia is pathogenetically close to arrhythmogenesis in patients with coronary heart disease.

Topics: Animals; Antioxidants; Arrhythmias, Cardiac; Ascorbic Acid; Calcium Chloride; Cell Membrane Permeability; Disease Models, Animal; Electrocardiography; Erythrocyte Membrane; Female; Humans; Iron Compounds; Lipid Peroxidation; Male; Malondialdehyde; Rats

Cardiac arrhythmias during ischemia/reperfusion are believed to be related to free radicals generated in the heart especially during the period of reperfusion. Since melatonin functions as a free radical scavenger and antioxidant, the ability of this molecule to influence cardiac arrhythmias was investigated. The pineal secretory product, melatonin, reduced the incidence and severity of arrhythmias induced by ischemia/reperfusion due to ligation of the anterior descending coronary artery in the isolated rat heart. Melatonin was either infused during both the ischemia and reperfusion periods or only late in the ischemia period and throughout reperfusion. The percentage of hearts that developed cardiac arrhythmias during reperfusion as indicated by the incidence of premature ventricular contraction (PVC) and ventricular fibrillation (VF) were recorded. Melatonin either infused during both the ischemia and reperfusion periods or during essentially the period of reperfusion greatly reduced PVC and VF due to occlusion and reopening the anterior descending coronary artery. Presumably melatonin's beneficial effect in reducing cardiac arrhythmias was due in part to its free radical scavenging activity, which is greatly assisted by the rapidity with which it is taken up into cells. Previous studies have shown that vitamin C is effective in reducing the severity of cardiac arrhythmias induced by ischemia/reperfusion; thus, we also compared the efficacy of melatonin with this well-known antioxidant. Melatonin was more potent than vitamin C in protecting against arrhythmias induced by ischemia/reperfusion. Besides melatonin's function as a broad spectrum free radical scavenger, melatonin may have also reduced cardiac arrhythmias due to its regulation of intracellular calcium levels, i.e., by preventing calcium overloading, or due to its ability to suppress sympathetic nerve function and reduce adrenergic receptor function in the myocardium. Additional studies into the mechanisms of melatonin's action in reducing cardiac arrhythmias due to ischemia/reperfusion or other causes are warranted because of the possible application of this information to humans with heart disease.

Topics: Animals; Antioxidants; Arrhythmias, Cardiac; Ascorbic Acid; Dose-Response Relationship, Drug; Free Radical Scavengers; Heart; Ischemia; Male; Melatonin; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion; Reperfusion Injury

Although the formation of oxygen-derived free radicals (or reactive oxygen species; ROS) and the release of endogenous opioid peptides (EOP) have been independently reported to be the major arrhythmogenic factors in ischemic hearts, possible relations between these two factors have seldom been investigated. Thus, we studied whether the ROS and EOP were related in the progression of ischemia-induced arrhythmias. Isolated rat hearts perfused in the Langendorff mode were treated with dynorphin A1-13 (kappa EOP receptor agonist), and/or allopurinol (xanthine oxidase inhibitor), before the onset of ischemia induced by ligating the left coronary arteries. Ischemic period lasted for 30 min, during which cardiac rhythms were recorded. At the end of ischemia, hearts were analyzed for the glutathione and ascorbate levels. Allopurinol (100 nmoles/heart) was effective in reducing the severity of arrhythmia (arrhythmia score: Mean +/- SEM 3.00 +/- 0.80 for allopurinol, 5.75 +/- 0.41 for placebo, p < 0.01), while dynorphin (10 micrograms/heart) potentiated the arrhythmia (6.71 +/- 0.52, p < 0.05 vs. placebo). Coadministration of allopurinol and dynorphin was capable of reducing arrhythmia (5.57 +/- 0.65) when compared with the administration of dynorphin alone (6.71 +/- 0.52, p < 0.05). Tissue oxidative stress was evaluated by the concentrations of glutathione (GSH) and ascorbate. Allopurinol did not significantly elevate tissue GSH concentrations (1.46 +/- 0.05 mumoles/g wet wt) in ischemic hearts, while dynorphin alone significantly decreased the GSH concentrations (0.96 +/- 0.08, p < 0.05) when compared with the placebo (1.32 +/- 0.03). The dynorphin-induced GSH decrease cannot be reversed by coadministration with allopurinol (0.90 +/- 0.104). Allopurinol significantly elevated tissue ascorbate levels (0.16 +/- 0.01) when compared with placebo (0.10 +/- 0.01, p < 0.05). Interestingly, dynorphin alone also elevated the tissue ascorbate concentrations (0.16 +/- 0.02). Coadministration of allopurinol and dynorphin further spiked the ascorbate levels (0.28 +/- 0.05, p < 0.01). In conclusion, the results suggested that ischemia-induced arrhythmia mechanisms might involve the formation of superoxide and other ROS, which were probably generated from the release of EOP (or EOP/EOP receptor interactions). Superoxide, the formation of which can be inhibited by allopurinol that exerted antiarrhythmic effect, was probably scavenged by ascorbate in myocardial ischemia. The ROS r

Topics: Allopurinol; Animals; Arrhythmias, Cardiac; Ascorbic Acid; Dynorphins; Female; Free Radicals; Glutathione; In Vitro Techniques; Models, Cardiovascular; Myocardial Ischemia; Opioid Peptides; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

Of 138 patients with suspected acute myocardial infarction (AMI), 29 were excluded. Remaining 109 patients and 182 healthy controls of similar age and sex and same population were studied in detail for demographic variables, clinical and biochemical data for comparison. Mean age, sex, body weight, body mass index and blood pressures were comparable in the two groups whereas blood lipids, blood glucose and cardiac enzymes were raised in AMI patients compared to controls. Mean levels of vitamin C, E, A and beta-carotene were significantly less in AMI patients than controls whereas the lipid peroxides were significantly higher in AMI patients. The reduction in vitamin C and beta-carotene was more marked than decrease in other vitamins. With in AMI patients, those 28 patients who had cardiac arrhythmias showed greater decrease in vitamins compared to rest of the patients. Within both groups, smokers and diabetes patients had greater reduction in vitamin C and beta-carotene than other patients and subjects without confounding factors. Smokers also had higher lipid peroxides level than non-smokers. The inverse relation between AMI and low plasma vitamin levels remained significant after exclusion of patients with smoking and diabetes. These findings suggest that vitamin deficiency may be a risk factor of AMI and these patients may benefit by administration of these antioxidant vitamins for primary and secondary prevention of coronary artery disease.

Topics: Antioxidants; Arrhythmias, Cardiac; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Female; Humans; Lipid Peroxides; Male; Middle Aged; Myocardial Infarction; Oxidative Stress; Prospective Studies; Vitamin A; Vitamin E; Vitamins

Structural modification of ascorbic acid by substitution of the 3-hydroxy group with lipophilic moieties has allowed the development of agents for treating reperfusion injury. These ascorbic acid derivatives inhibited lipid peroxidation, and some of them also reduced coronary reperfusion-induced arrhythmias in anesthetized rats. We found that 3-O-[(dodecylcarbonyl)methyl]ascorbic acid (8) was protective against reperfusion injury without directly influencing hemodynamics. 2-O-Octadecylascorbic acid (19) and 5,6-O-dodecylideneascorbic acid (15) also exhibited a marked effect on reperfusion injury, but significantly reduced the arterial blood pressure and heart rate in rats.

Topics: Anesthesia; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Ascorbic Acid; Blood Pressure; Free Radical Scavengers; Guinea Pigs; Heart Atria; Heart Rate; In Vitro Techniques; Lipid Peroxidation; Microsomes, Liver; Myocardial Reperfusion Injury; Rats; Rats, Inbred Strains; Verapamil

The cardioprotective effects of a high dose of ascorbate on ischemia-reperfusion-induced myocardial damage were investigated using open chest anesthetized dogs. Two-hour occlusion of the left anterior descending coronary artery (LAD) induced mitochondrial dysfunction with a depletion of mitochondrial glutathione (GSH) concentration. Two-hour LAD occlusion followed by 1-h reperfusion worsened the ischemia-induced mitochondrial dysfunction together with a marked depletion of mitochondrial GSH concentration. Ascorbate reduced the mitochondrial dysfunction and prevented the depletion of mitochondrial GSH concentration after 2-h LAD occlusion and 1-h reperfusion. Activities of mitochondrial glutathione peroxidase and glutathione reductase did not change significantly in each group. Administration of ascorbate also prevented reperfusion arrhythmias without affecting blood pressure or heart rate. These results suggest that coronary reperfusion induces mitochondrial dysfunction and a depletion of mitochondrial GSH concentration, and that a high dose of ascorbate prevents reperfusion damage.

Topics: Animals; Arrhythmias, Cardiac; Ascorbic Acid; Coronary Disease; Dogs; Dose-Response Relationship, Drug; Energy Metabolism; Female; Free Radicals; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Male; Mitochondria, Heart; Myocardial Reperfusion Injury

The effects of pretreatment with 2-O-octadecylascorbic acid (CV-3611), a novel liposoluble free radical scavenger, on reperfusion-induced arrhythmias were studied in isolated perfused rat hearts (n = 15 per group). The hearts were subjected to 10 min of coronary artery occlusion and 3 min of reperfusion. Pretreatment with CV-3611 (5 and 20 mg/kg) reduced the incidence of ventricular fibrillation (VF; reversible plus sustained) from its control value of 93% to 47% (p less than 0.05). Furthermore, CV-3611 reduced the incidence of sustained VF in a dose-dependent manner, from 67% in the control group to 13% in the CV-3611, 20 mg/kg treated group (p less than 0.01). CV-3611 (5 and 20 mg/kg) reduced the incidence of ventricular tachycardia (VT) from its control value of 93% to 73%. Pretreatment with ascorbic acid (5 mg/kg) had no effect on VF and VT. The myocardial content of CV-3611 was proportional to the dosage. We concluded that CV-3611 could reduce significantly the susceptibility to reperfusion-induced arrhythmias, especially VF, and that its effect may be due to the elimination of oxygen-derived free radicals by CV-3611 present in the membrane and the capture of lipid radicals, thereby inhibiting lipid peroxidation.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Ascorbic Acid; Coronary Circulation; Coronary Disease; Coronary Vessels; Electrocardiography; Free Radical Scavengers; Heart; Heart Rate; In Vitro Techniques; Male; Myocardial Reperfusion; Myocardium; Perfusion; Rats; Rats, Inbred Strains

A novel series of 2-O-alkylascorbic acids (5a-u) was synthesized, and their scavenging activities against active oxygen species as well as their suppressive effects on the arrhythmias in rat heart ischemia-reperfusion models were evaluated. Some 2-O-alkylascorbic acids (5e-1) exhibited potent inhibiting activities against lipid peroxidation in rat brain homogenates and in alleviating effects in the ischemia-reperfusion models. Studies on the structure-activity relationship demonstrated that a free 3-enolic hydroxyl group and the longer alkyl chains substituted on the 2-hydroxyl group of ascorbic acid were beneficial for the biological and pharmacological activities. 2-O-Octadecylascorbic acid (5k, CV-3611), one of the most potent and promising compounds, markedly inhibited lipid peroxidation (IC50 = 4.3 X 10(-6) M) and alleviated myocardial lesions induced by ischemia-reperfusion at an oral dose of 1 mg/kg in rats.

Topics: Animals; Arrhythmias, Cardiac; Ascorbic Acid; Heart Rate; Ligation; Linoleic Acid; Linoleic Acids; Lipid Peroxides; Male; Micelles; Oxygen; Rats; Structure-Activity Relationship

The possible role of oxygen free radicals in the development of reperfusion arrhythmias was investigated using a 10-min period of coronary ligation followed by reperfusion in the isolated rat heart. Superoxide dismutase (5 to 20 u/ml) glutathione (10(-5) to 10(3)M) and ascorbic acid (10(-4) to 5 X 10(-4) M) when given before coronary ligation attenuated the development of reperfusion arrhythmias. Mannitol (2 X 10(-2)M) and catalase (100 and 300 u/ml) did not have any significant effect on reperfusion arrhythmias when given alone but they did potentiate the antiarrhythmic effect of superoxide dismutase. Glutathione, and a combination of superoxide dismutase, catalase and mannitol also reduced the incidence of reperfusion induced ventricular fibrillation when given just before reperfusion. By perfusing hearts with ferricytochrome C it was possible to show an increased reduction of ferricytochrome C during the first minute of reperfusion which could be prevented by the addition of superoxide dismutase. These results provide evidence that oxygen free radicals are produced and may be important in the genesis of reperfusion induced arrhythmias in the isolated rat heart.

Topics: Animals; Arrhythmias, Cardiac; Ascorbic Acid; Catalase; Coronary Circulation; Drug Combinations; Free Radicals; Glutathione; Heart; In Vitro Techniques; Ligation; Male; Mannitol; Oxygen; Perfusion; Rats; Rats, Inbred Strains; Superoxide Dismutase