ascorbic-acid and Myocardial-Infarction

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.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Biomarkers; Deferoxamine; Dose-Response Relationship, Drug; Drug Synergism; Female; Humans; Male; Myocardial Infarction; Oxidative Stress; Percutaneous Coronary Intervention; Polyphenols; Protective Agents; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction; Stroke Volume; Tocopherols; Ventricular Function, Left

For decades, there has been epidemiologic evidence linking chronic toxic metal exposure with cardiovascular disease, suggesting a therapeutic role for metal chelation. Given the lack of compelling scientific evidence, however, the indications for metal chelation were never clearly defined. To determine the safety and efficacy of chelation therapy, the National Institutes of Health funded the Trial to Assess Chelation Therapy (TACT). TACT was the first double-blind, randomized, controlled trial to demonstrate an improvement in cardiovascular outcomes with edetate disodium therapy in patients with prior myocardial infarction. The therapeutic benefit was striking among the prespecified subgroup of patients with diabetes.. We review the published literature focusing on the atherogenic nature of diabetes, as well as available evidence from clinical trials, complete and in progress, of metal chelation with edetate disodium therapy in patients with diabetes.. The TACT results support the concept that ubiquitous toxic metals such as lead and cadmium may be modifiable risk factors for cardiovascular disease, particularly in patients with diabetes.. The purpose of this review is to discuss the potential mechanisms unifying the pathogenesis of atherogenic factors in diabetes with toxic metal exposure, and the potential role of metal chelation.

Topics: Antioxidants; Arsenic; Ascorbic Acid; Atherosclerosis; Cadmium; Calcium Chelating Agents; Cardiovascular Diseases; Chelating Agents; Chelation Therapy; Copper; Diabetes Complications; Diabetes Mellitus; Edetic Acid; Glycation End Products, Advanced; Hospitalization; Humans; Iron; Lead; Lipid Metabolism; Mercury; Myocardial Infarction; Myocardial Revascularization; Oxidative Stress; Randomized Controlled Trials as Topic; Stroke

Vitamin C is an essential micronutrient and powerful antioxidant. Observational studies have shown an inverse relationship between vitamin C intake and major cardiovascular events and cardiovascular disease (CVD) risk factors. Results from clinical trials are less consistent.. To determine the effectiveness of vitamin C supplementation as a single supplement for the primary prevention of CVD.. We searched the following electronic databases on 11 May 2016: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (Ovid); Embase Classic and Embase (Ovid); Web of Science Core Collection (Thomson Reuters); Database of Abstracts of Reviews of Effects (DARE); Health Technology Assessment Database and Health Economics Evaluations Database in the Cochrane Library. We searched trial registers on 13 April 2016 and reference lists of reviews for further studies. We applied no language restrictions.. Randomised controlled trials of vitamin C supplementation as a single nutrient supplement lasting at least three months and involving healthy adults or adults at moderate and high risk of CVD were included. The comparison group was no intervention or placebo. The outcomes of interest were CVD clinical events and CVD risk factors.. Two review authors independently selected trials for inclusion, abstracted the data and assessed the risk of bias.. We included eight trials with 15,445 participants randomised. The largest trial with 14,641 participants provided data on our primary outcomes. Seven trials reported on CVD risk factors. Three of the eight trials were regarded at high risk of bias for either reporting or attrition bias, most of the 'Risk of bias' domains for the remaining trials were judged as unclear, with the exception of the largest trial where most domains were judged to be at low risk of bias.The composite endpoint, major CVD events was not different between the vitamin C and placebo group (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.89 to 1.10; 1 study; 14,641 participants; low-quality evidence) in the Physicians Health Study II over eight years of follow-up. Similar results were obtained for all-cause mortality HR 1.07, 95% CI 0.97 to 1.18; 1 study; 14,641 participants; very low-quality evidence, total myocardial infarction (MI) (fatal and non-fatal) HR 1.04 (95% CI 0.87 to 1.24); 1 study; 14,641 participants; low-quality evidence, total stroke (fatal and non-fatal) HR 0.89 (95% CI 0.74 to 1.07); 1 study; 14,641 participants; low-quality evidence, CVD mortality HR 1.02 (95% 0.85 to 1.22); 1 study; 14,641 participants; very low-quality evidence, self-reported coronary artery bypass grafting (CABG)/percutaneous transluminal coronary angioplasty (PTCA) HR 0.96 (95% CI 0.86 to 1.07); 1 study; 14,641 participants; low-quality evidence, self-reported angina HR 0.93 (95% CI 0.84 to 1.03); 1 study; 14,641 participants; low-quality evidence.The evidence for the majority of primary outcomes was downgraded (low quality) because of indirectness and imprecision. For all-cause mortality and CVD mortality, the evidence was very low because more factors affected the directness of the evidence and because of inconsistency.Four studies did not state sources of funding, two studies declared non-commercial funding and two studies declared both commercial and non-commercial funding.. Currently, there is no evidence to suggest that vitamin C supplementation reduces the risk of CVD in healthy participants and those at increased risk of CVD, but current evidence is limited to one trial of middle-aged and older male physicians from the USA. There is limited low- and very low-quality evidence currently on the effect of vitamin C supplementation and risk of CVD risk factors.

Topics: Angioplasty, Balloon, Coronary; Ascorbic Acid; Cardiovascular Diseases; Coronary Artery Bypass; Dietary Supplements; Humans; Male; Middle Aged; Myocardial Infarction; Physicians; Primary Prevention; Publication Bias; Randomized Controlled Trials as Topic; Stroke; Vitamins

Topics: Ascorbic Acid; Dietary Supplements; Evidence-Based Medicine; Humans; Myocardial Infarction; Osteopathic Physicians; Physician-Patient Relations; Risk Factors; Vitamin B Complex; Vitamin E; Vitamins

Acute myocardial infarction (MI) is one of the most frequent causes of death in the United States. The evaluation and treatment of acute MI in conventional medicine has focused primarily on anatomical and physiological factors that lead to impaired blood flow. Less attention has been paid to metabolic factors that may influence the vulnerability of the myocardium to ischemia and to various stressors. There is evidence that in some cases inefficient cellular metabolism, rather than the availability of oxygen and other blood-borne nutrients, is an important factor determining whether cardiac pathology will develop. Metabolic dysfunction could result from intracellular deficiencies of magnesium, coenzyme Q10, carnitine, and certain B vitamins, nutrients which play a role in the synthesis of adenosine triphosphate (ATP; the body's main storage form of energy). In addition, increased oxidative stress may contribute to the pathogenesis of both MI-related myocardial damage and reperfusion injury. Consequently, administration of antioxidants might improve outcomes in patients with acute MI. Numerous clinical trials have found parenteral administration of magnesium in the early stages of acute MI can substantially reduce the death rate. In addition, several trials have shown L-carnitine is beneficial in the treatment of acute MI. Other nutrients, such as vitamin C, vitamin E, and various B vitamins, may also be of value.

Topics: Antioxidants; Ascorbic Acid; Carnitine; Dietary Supplements; Humans; Magnesium; Myocardial Infarction; Oxidative Stress; Primary Prevention; Ubiquinone; United States; Vitamin B Complex; Vitamin E

There is a growing body of evidence for the role of free radicals in mediating myocardial tissue injury during myocardial ischemia and in particular during the phase of myocardial reoxygenation. Associated with myocardial ischemia and reperfusion is the generation of oxygen-derived free radicals from a variety of sources that include the mitochondrial electron transport chain; the biosynthesis of prostaglandins; the enzyme xanthine oxidase; and circulating elements in the blood, with the polymorphonuclear neutrophil assuming a primary focus of attention. Experimental studies have shown that free radical scavengers (e.g., N-[2-mercaptopropionyl]glycine) and enzymes that scavenge or degrade reactive species of oxygen (superoxide dismutase or catalase) can reduce the mass of myocardial tissue that undergoes irreversible injury. Additionally allopurinol, which inhibits the enzyme xanthine oxidase, reduces ultimate infarct size, putatively by reducing the xanthine oxidase generation of superoxide anion. Neutrophils that enter the ischemically injured myocardium under the influence of chemotactic attraction and activation of the complement system generate and release highly reactive and cytotoxic oxygen derivatives that are destructive to the vascular endothelium and to the cardiac myocytes. Studies have documented that neutrophil depletion or suppression of neutrophil function (ibuprofen, nafazatrom, BW 755C, or more recently with prostacyclin or iloprost) results in a significant salvage of myocardial tissue that is subjected to a period of regional ischemia followed by reperfusion. Our current understanding of the events associated with myocardial ischemia suggests that within the ischemic myocardial region or area at risk, there is a population of cells that are reversibly injured and that reperfusion within a specified period (less than 3 hours) of time is capable of restoring the majority of the jeopardized cells to a normal status, but that the act of reperfusion itself will lead to the sudden demise of a fraction of the cells because of the cytotoxic effects of reactive species of oxygen derived from one or more of the sources indicated above. The efforts to minimize the amount of tissue that undergoes cell death as a result of myocardial ischemia demand that early reperfusion be established. However, the reintroduction of molecular oxygen and the circulating elements of the blood will be associated with an "explosive" and self-limited destruction of so

Topics: Antioxidants; Ascorbic Acid; Cell Adhesion; Coronary Disease; Free Radicals; Glycoproteins; Humans; Lysosomes; Myocardial Infarction; Myocardium; Necrosis; Neutrophils; Oxygen; Superoxide Dismutase; Xanthine Oxidase

Reactive oxygen metabolic products derived from an activated NADPH oxidase present in the cell membrane of PMNs and mononuclear phagocytic cells play a critical role in the host's defense against bacterial infection. Recent studies have also demonstrated the ability of these toxic products to initiate eukaryotic cell injury and promote the development of the acute inflammatory responses. Experimental studies suggest that neutrophil-derived oxygen metabolites contribute to the development of the tissue injury associated with a variety of disease states, including emphysema, myocardial infarction, adult respiratory distress syndrome, immune complex-mediated vasculitis, and rheumatoid arthritis. Future studies to define further the mechanisms by which reactive oxygen-derived metabolic products mediate tissue injury will provide insight into the development of new therapeutic strategies for the modulation of disease states that are mediated by the recruitment and activation of PMNs.

Topics: Animals; Arthritis, Rheumatoid; Ascorbic Acid; Autoimmune Diseases; Ceruloplasmin; Chemotactic Factors; Cricetinae; Cricetulus; Free Radicals; Humans; Immune Complex Diseases; Inflammation; Lipid Peroxides; Myocardial Infarction; NADH, NADPH Oxidoreductases; NADPH Oxidases; Neutrophils; Oxidation-Reduction; Oxygen; Pancreatic Elastase; Peroxidase; Peroxidases; Peroxides; Phagocytosis; Pulmonary Emphysema; Respiratory Distress Syndrome; Superoxide Dismutase; Superoxides; Vasculitis; Vitamin E

Topics: Androgens; Animals; Ascorbic Acid; Carbon Isotopes; DNA; Dogs; Fibroblasts; Growth Hormone; Heart; Hexoses; Lipids; Myocardial Infarction; Myocardium; Protein Biosynthesis; RNA; Time Factors

Topics: Adult; Aged; Animals; Arteriosclerosis; Ascorbic Acid; Catecholamines; Diet Therapy; Dietary Fats; Fats, Unsaturated; Female; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertension; Injections, Intra-Arterial; Intermittent Claudication; Male; Mice; Middle Aged; Myocardial Infarction; Nicotine; Obesity; Procaine; Rabbits; Radiography; Smoking; Sympathectomy; Thiamine; Thromboangiitis Obliterans; Tolazoline; Vasodilator Agents

Percutaneous coronary angioplasty (PCA) has been demonstrated to reduce mortality and morbidity and thereby improve the prognosis of patients undergoing acute myocardial infarctions (AMIs). However, this procedure paradoxically increases the initial damage as the result of a condition known as 'myocardial reperfusion injury'. Oxidative stress may contribute to the mechanism of this injury. The goal of the present study was to ascertain whether high plasma ascorbate levels could ameliorate the reperfusion injuries that occur after the successful restoration of blood flow.. Patients from three clinical centers of the public health system were included in the study. The groups were formed by either-sex patients with a diagnosis of ST-segment elevation myocardial infarction with an indication for primary PCA. Only the patients who presented with their first myocardial infarction were enrolled. Ascorbate was administered through an infusion given prior to the restoration of the coronary flow, which was then followed by oral treatment with vitamin C (500 mg/12 hours) plus vitamin E (400 IU/day) for 84 days. The left ventricular ejection fraction (LVEF) was determined by using cardiac magnetic resonance on days 6 and 84 following the onset of the reperfusion. In addition, the microvascular function was assessed by an angiographic evaluation using the Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade (TMPG). The results were grouped according to the plasma ascorbate concentration achieved immediately following the onset of reperfusion into either the HA group (high ascorbate, >1 mmol/l) or the LA group (low ascorbate, <1 mmol/l). The biochemical parameters were analyzed throughout the protocol.. The LVEF of the HA group was significantly higher than that of the LA group, values on day 84 in the HA group were 33% higher than those of the LA group. The amelioration of the LVEF was accompanied by an improvement in the microvascular dysfunction, after PCA, 95% of the patients in the HA group achieved a TMPG of 2-3, in the LA group only 79% of patients showed a TMPG of 2-3.. These data are consistent with the protective effect of high plasma levels of ascorbate against the oxidative challenge caused by reperfusion injury in patients subjected to PCA following an AMI. Further studies are needed to elucidate the mechanism accounting for this beneficial antioxidant effect.

Topics: Aged; Angioplasty, Balloon, Coronary; Ascorbic Acid; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion Injury; Oxidative Stress; Ventricular Function, Left

Acute myocardial infarction (AMI) is the leading cause of mortality worldwide. Oxidative stress has been involved in the ischemia-reperfusion injury in AMI. It has been suggested that reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented.Therefore, we propose that antioxidant reinforcement through vitamins C and E supplementation should protect against the ischemia-reperfusion damage, thus decreasing infarct size.The PREVEC Trial (Prevention of reperfusion damage associated with percutaneous coronary angioplasty following acute myocardial infarction) seeks to evaluate whether antioxidant vitamins C and E reduce infarct size in patients subjected to percutaneous coronary angioplasty after AMI.. This is a randomized, 1:1, double-blind, placebo-controlled clinical trial.The study takes place at two centers in Chile: University of Chile Clinical Hospital and San Borja Arriarán Clinical Hospital.The subjects will be 134 adults with acute myocardial infarction with indication for percutaneous coronary angioplasty.This intervention is being performed as a pilot study, involving high-dose vitamin C infusion plus oral administration of vitamin E (Vitamin-treatment group) or placebo (Control group) during the angioplasty procedure. Afterward, the Vitamin-treatment group receives oral doses of vitamins C and E, and the Control group receives placebo for 84 days after coronary angioplasty.Primary outcome is infarct size, assessed by cardiac magnetic resonance (CMR), measured 6 and 84 days after coronary angioplasty.Secondary outcomes are ejection fraction, measured 6 and 84 days after coronary angioplasty with CMR, and biomarkers for oxidative stress, antioxidant status, heart damage, and inflammation, which will be measured at baseline, at the onset of reperfusion, 6 to 8 hours after revascularization, and at hospital discharge.. The ischemia-reperfusion event occurring during angioplasty is known to increase myocardial infarct size. The cardioprotective benefits of high doses of vitamin C combined with vitamin E have not been fully explored. The PREVEC Trial seeks to determine the suitability of the therapeutic use of vitamins C and E against the reperfusion damage produced during angioplasty.Patient recruitment opened in February 2013. The trial is scheduled to end in March 2016.. ISRCTN56034553.

Topics: Administration, Oral; Antioxidants; Ascorbic Acid; Biomarkers; Chile; Clinical Protocols; Double-Blind Method; Drug Administration Schedule; Female; Hospitals, University; Humans; Magnetic Resonance Imaging; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Percutaneous Coronary Intervention; Pilot Projects; Research Design; Time Factors; Treatment Outcome; Vitamin E

Topics: Ascorbic Acid; Chelating Agents; Chelation Therapy; Edetic Acid; Humans; Myocardial Infarction; National Heart, Lung, and Blood Institute (U.S.); United States; Vitamin B Complex; Vitamins

Recent studies indicated that excessive oxidative stress in an animal heart failure model injures both the sympathetic nerve endings and receptors, resulting in disturbance of norepinephrine release and sensitivity to norepinephrine. However, it has not been clarified whether this phenomenon is expressed clinically in patients with heart disease. Therefore, we examined the efficacy of ascorbic acid administration as an antioxidant vitamin in relation to the heart rate and norepinephrine response to exercise in patients after myocardial infarction.. In this randomized crossover trial, 21 male patients who had had myocardial infarction underwent symptom-limited ergometer cardiopulmonary exercise testing twice, that is, without and with ascorbic acid (2 g) administration. Plasma norepinephrine concentrations were assessed at rest and at peak exercise, and heart rate responsiveness to the norepinephrine increment from rest to peak exercise (DeltaHR/logDeltaNE) was calculated.. In the exercise test after ascorbic acid administration, peak oxygen consumption (VO(2)) improved over baseline. Ascorbic acid administration significantly increased the change in heart rate and norepinephrine from rest to peak exercise and DeltaHR/logDeltaNE. The increment in heart rate was significantly correlated with peak VO(2) in each test.. Ascorbic acid intake before exercise improved exercise capacity through enhancement of the heart rate and norepinephrine response to exercise in patients after myocardial infarction. These findings suggest that ascorbic acid intake improves sympathetic dysfunction resulting from injury by excessive oxidative stress after myocardial infarction.

Topics: Aged; Ascorbic Acid; Cross-Over Studies; Exercise; Exercise Test; Heart Rate; Humans; Male; Middle Aged; Myocardial Infarction; Norepinephrine; Oxygen Consumption; Rest; Sympathetic Nervous System

Reperfusion injury causes oxidative stress thereby resulting in an imbalance between oxidant-antioxidant systems. In the present communication, the effect of ascorbic acid supplementation has been studied on certain oxidant and antioxidant parameters in the blood of the patients with myocardial infarction before and after thrombolysis. In patients after thrombolysis, the activity of antioxidant enzyme, superoxide dismutase, in the blood was found to be significantly reduced where as the activity of the oxidant enzyme, xanthine oxidase, was found to be significantly increased. Malondialdehyde levels, the index of free radical mediated damage, was also found to be significantly elevated in thrombolysed patients compared to the patients before thrombolysis. Supplementation of vitamin C to the post reperfusion patients restored these parameters back to normal or near normal levels.

Topics: Ascorbic Acid; Humans; Malondialdehyde; Myocardial Infarction; Myocardial Reperfusion; Oxidative Stress; Reactive Oxygen Species; Reperfusion; Superoxide Dismutase; Xanthine Oxidase

There is a large body of evidence that reactive oxygen species (ROS) produced during myocardial ischemia and reperfusion play a crucial role in myocardial damage and endothelial dysfunction. The MIVIT pilot trial was designed to test the effects of antioxidant vitamins C and E on the clinical outcome of patients with AMI.. In this randomized, double-blind, multicenter trial, 800 patients (mean age 62) with AMI were randomly allocated to receive, on top of routine medication, one of two treatments: vitamin C (1000 mg/12 h infusion) followed by 1200 mg/24 h orally and vitamin E (600 mg/24 h) or matching placebo for 30 days. Primary end point (composite of in-hospital cardiac mortality, non-fatal new myocardial infarction, VT/VF/asystole, shock/pulmonary edema) occurred less frequently in patients treated with antioxidants (55 [14%] vs 75 [19%], OR 0.82 [95% CI, 0.68-1.00], p=0.048).. This randomized pilot trial shows that supplementation with antioxidant vitamins is safe and seems to positively influence the clinical outcome of patients with AMI. A larger study is warranted to provide further evidence of this promising and inexpensive regimen.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Double-Blind Method; Drug Administration Schedule; Female; Hospital Mortality; Humans; Male; Middle Aged; Myocardial Infarction; Pilot Projects; Poland; Reactive Oxygen Species; Treatment Outcome; Vitamin E

We have investigated the effect of modest supplementation with alpha-tocopherol (100 mg/day), beta-carotene (6 mg/day), vitamin C (100 mg/day) and selenium (50 microg/day) on oxidative stress and chromosomal damage, and the influence of methylenetetrahydrofolate reductase (MTHFR) genotype on these end-points. Subjects were two groups of middle-aged men differing in cardiovascular risk; 46 survivors of myocardial infarction before age 50 and 60 healthy controls. They were randomly divided into equal groups to receive antioxidants or placebo for 12 weeks. Twenty-eight patients and 58 controls completed the intervention. Micronucleus levels in peripheral lymphocytes and changes seen after intervention were studied in relation to the MTHFR C677T genotype, basal homocysteine and plasma folate levels. Ferric reducing ability of plasma and concentration of malondialdehyde were measured to assess the antioxidant effect of supplementation. There was no association of micronuclei with folate, homocysteine or malondialdehyde levels before supplementation. Micronucleus frequencies and plasma folate levels did not vary significantly with MTHFR genotype. Homocysteine levels in subjects with the TT variant genotype were significantly higher compared with CT or CC (P = 0.001), especially in subjects with low folate (P = 0.012). In the placebo control group an increase in micronuclei (P = 0.04) was detected at the end of the intervention period. This effect was not seen in the supplemented group. In antioxidant-supplemented myocardial infarction survivors we found an increase in the ferric reducing ability of plasma (P < 0.001) and a decrease in malondialdehyde (P = 0.001). Micronucleus frequency showed a decrease, strongest in subjects with normal folate levels (P = 0.015). In subjects with low folate levels, a high correlation was found between micronuclei after supplementation and homocysteine, both before (r = 0.979, P = 0.002) and after supplementation (r = 0.922, P = 0.009). Thus, folate deficiency may amplify the effect of other risk factors such as elevated homocysteine levels or variant MTHFR genotype, as well as influencing the ability of antioxidant supplementation to protect against genetic damage.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Dietary Supplements; DNA Damage; Folic Acid; Folic Acid Deficiency; Genotype; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Micronucleus Tests; Middle Aged; Myocardial Infarction; Oxidative Stress; Selenium

During myocardial infarction (MI), high levels of circulating procoagulant microparticles (MP) shed from endothelial cells and platelets diffuse prothrombotic and proinflammatory potentials crucial for the coronary prognosis. In addition to conventional treatments, we evaluated whether vitamin C treatment could modify circulating levels of procoagulant MP. Upon admission, 61 patients with MI were prospectively randomized for immediate additional vitamin C treatment. Circulating MP were quantified by functional prothrombinase assay before and after 5 days of vitamin C administration (1 g day-1). The cellular origin of MP was also assessed. In vitamin C-treated patients, the reduction in platelet-derived MP was 10% higher (P = 0.01). In patients with diabetes mellitus, dyslipidemia or more than two cardiovascular risk factors, vitamin C decreased endothelial and platelet-derived MP levels by approximately 70% and 13%, respectively. This early effect on circulating platelet and endothelial-derived MP, testifies to the importance of oxidative stress during MI. Vitamin C could prove beneficial for the outcome of patients at higher thrombotic risk.

Topics: Acute Disease; Aged; Ascorbic Acid; Blood Platelets; Cardiotonic Agents; Coronary Angiography; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Activation; Prospective Studies; Risk Factors; Thromboplastin

Antioxidant vitamins C and E inhibit neutrophil-mediated production of free radicals in acute myocardial infarction (MI) which may limit MI size and improve myocardial perfusion.. To examine whether treatment with vitamin C and E reduces inhomogeneity of repolarisation in patients with acute MI.. In this double-blind, placebo-controlled randomised trial 37 patients with acute MI were enrolled and assigned to vitamin C and E (600 mg/day each) or placebo treatment, starting on the first day of acute MI and lasting for 14 days. Inhomogeneity of repolarisation was assessed by examining QT interval dispersion (QTd), measured both at rest and at the end of sub-maximal exercise test, performed before discharge.. Baseline QTd was similar in both groups, however, exercise-induced QTd was significantly lower in patients treated with antioxidant vitamins compared with the placebo group (59 +/- 20 msec vs 74 +/- 24 msec, p<0.05).

Topics: Antioxidants; Ascorbic Acid; Double-Blind Method; Electrocardiography; Exercise Test; Female; Free Radicals; Humans; Male; Middle Aged; Myocardial Infarction; Vitamin E

The role of reactive oxygen products in myocardial damage caused by ischemia-reperfusion has been established in a number of studies performed in animals models. However, studies showing the development of increased free radicals following effective myocardial reperfusion in humans are scarce. In the present study, both the increase of lipid peroxidation (LPO) following early stage thrombolytic therapy which is the current treatment issue performed after acute myocardial infarct (AMI) and the plasma levels of vitamin E and C (chain braker antioxidants) were investigated parallel to time. Forty patients with AMI who were admitted to hospital within six hours from the beginning of symptoms were included in the study and divided into two groups; group 1 (recombinant tissue-Plasminogen Activator, rt-PA group) and group 2 (streptokinase group). Serial serum specimens were drawn before and 30, 90 minutes and 24 hours after thrombolytic therapy for the investigation of LPO, vitamin E and C levels. Echocardiographic examination was performed on the tenth day to evaluate the functions of the left ventricle. Plasma levels of lipid peroxides (LPO) were found to increase 90 minutes after thrombolytic therapy in each group, while the levels of vitamins E and C showed significant decreases. The difference between the two groups was not significant. Similar to this finding, no significant difference in the ejection fraction values was observed between the groups. Further, no correlation was observed between the ejection fraction and LPO values at the 90th minute which is considered to be the time of successful thrombolysis. In conclusion, the occurrence of a series of biochemical changes confirming an increase in free radical development of peripheral blood was observed. Although the decrease in vitamin E and C levels suggests the need for supplementation of these vitamins along with the thrombolytic therapy, the fact that at least a week is needed for an increase of tissue levels of vitamin E confirms the opinion that the daily prophylactic doses of these vitamins is suitable for the decrease of AMI risk.

Topics: Antioxidants; Ascorbic Acid; Fibrinolytic Agents; Free Radicals; Humans; Lipid Peroxidation; Lipid Peroxides; Malondialdehyde; Myocardial Infarction; Recombinant Proteins; Streptokinase; Thrombolytic Therapy; Tissue Plasminogen Activator; Ventricular Function, Left; Vitamin E

Reactive oxygen species are thought to mediate reperfusion injury after rapid revascularization for acute myocardial infarction (AMI) and 8-epi prostaglandin (PG) F2alpha, a free-radical catalyzed product of arachidonic acid, has been proposed as an indicator of oxidative stress in vivo during myocardial reperfusion. The time course of urinary 8-epi PGF2alpha excretion after primary coronary angioplasty (PTCA) for AMI was investigated, as well as the effect of prior administration of vitamin C. Urine samples, 1 before and 5 after primary PTCA (0-30, 30-60, 60-90, 90-120 and 120-150 min), were collected in 11 patients with AMI undergoing primary PTCA (Group 1), 10 patients with AMI treated with water-soluble vitamin C at an initial dose of 2.0 g followed by a constant infusion at 20mg/min prior to primary PTCA (Group 2), and 6 patients with stable effort angina undergoing elective PTCA (Group 3). 8-epi PGF2alpha was measured by enzyme immunoassay. There were no significant differences in urinary 8-epi PGF2alpha excretion at baseline among the 3 groups. In Group 1, urinary 8-epi PGF2alpha excretion (ng/mmol creatinine) significantly increased from 60+/-8 at baseline to 122+/-16 at 60-90 min (p<0.001), and declined to the baseline level at 120-150 min after primary PTCA. In Group 2, it also increased from 72+/-12 to 123+/-15 at 60-90 min (p<0.01), and the percent increase did not differ from that in Group 1. In Group 3, it remained unchanged during the study period. The free radical production is rapidly and transiently enhanced after primary PTCA for AMI, and vitamin C fails to suppress it.

Topics: Aged; Angioplasty, Balloon, Coronary; Antioxidants; Ascorbic Acid; Dinoprost; F2-Isoprostanes; Female; Free Radicals; Humans; Male; Middle Aged; Myocardial Infarction

An increase in blood level of Cortisol and overproduction of free radicals is present during first days following acute ischemia and myocardial infarction. This increase exceeds the activity of protective compounds and systems of myocardial cells undergoing ischemia. The aim of this work was to study the relationship between the Cortisol blood level and the intensity of free radical reactions in patients with acute myocardial ischemia and acute myocardial infarction with respect to metabolic (glucose, uric acid) and enzymatic agents of ischemia and necrosis. The study was performed in 75 patients (20 females and 55 males) aged 38-75 years, including 13 patients with acute myocardial ischemia (6 females and 7 males) aged 40-66 years (group I), 40 patients with acute myocardial infarction (8 females and 32 males) aged 38-72 years (group II) and 22 healthy volunteers (6 females and 16 males) aged 39-75 years (control group). The concentration of Cortisol in blood and other biochemical determinants were measured on the second, fifth and seventh day following admission to the coronary care unit. The intensity of free radicals reactions was measured by using the concentration of Vitamin C, malondialdehyde (MDA), uric acid and white blood cells (WBC) count as markers. The results obtained have led to the following conclusions: 1. The increase in blood level of Cortisol in acute myocardial infarction is higher in comparison to the level of Cortisol in acute myocardial ischemia. 2. The intensity of free radical reactions during acute myocardial ischemia and acute myocardial infarction can be assessed by the decreased level of Vitamin C, increased level of malondialdehyde, uric acid concentration and leukocyte (WBC) count. 3. There is no correlation between the intensity of free radical reactions and elevation of blood cortisol during both acute myocardial ischemia and acute myocardial infarction. 4. Elevated levels of Cortisol in blood correlate with elevated levels of glucose and uric acid in blood during both acute myocardial ischemia and acute myocardial infarction. 5. Increase in enzymatic markers of ischemia and necrosis during acute myocardial ischemia and necrosis shows no correlation with the intensity of free radicals reactions.

Topics: Adult; Aged; Ascorbic Acid; Female; Free Radicals; Humans; Hydrocortisone; Leukocyte Count; Male; Malondialdehyde; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Uric Acid

In a randomized, double-blind, placebo-controlled trial, the effects of combined treatment with the antioxidant vitamins A (50,000 IU/day), vitamin C (1,000 mg/day), vitamin E (400 mg/day), and beta-carotene (25 mg/day) were compared for 28 days in 63 (intervention group) and 62 (placebo group) patients with suspected acute myocardial infarction. After treatment with antioxidants, the mean infarct size (creatine kinase and creatine kinase-MB gram equivalents) was significantly less in the antioxidant group than in the placebo group. Serum glutamic-oxaloacetic transaminase decreased by 45.6 IU/dl in the antioxidant group versus 25.8 IU/dl in the placebo group (p < 0.02). Cardiac enzyme lactate dehydrogenase increased slightly (88.6 IU/dl) in the antioxidant group compared with that in the placebo group (166.5 IU/dl) (p < 0.01). QRS score in the electrocardiogram was significantly less in the antioxidant than in the placebo group. The following levels increased in the antioxidant group versus the placebo group, respectively: plasma levels of vitamin E increased by 8.8 and 2.2 mumol/L (p < 0.01), vitamin C increased by 12.6 and 4.2 mumol/L (p < 0.01), beta-carotene increased by 0.28 and 0.06 mumol/L (p < 0.01), and vitamin A increased by 0.36 and 0.12 mumol/L (p < 0.01). Serum lipid peroxides decreased by 1.22 pmol/ml in antioxidant versus 0.22 pmol/ml in the placebo group (p < 0.01). Angina pectoris, total arrhythmias, and poor left ventricular function occurred less often in the antioxidant group. Cardiac end points were significantly less in the antioxidant group (20.6% vs 30.6%, respectively). These results suggest that combined treatment with antioxidant vitamins A, E, C, and beta-carotene in patients with recent acute myocardial infarction may be protective against cardiac necrosis and oxidative stress, and could be beneficial in preventing complications and cardiac event rate in such patients.

Topics: Adult; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; beta Carotene; Carotenoids; Creatine Kinase; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Female; Humans; L-Lactate Dehydrogenase; Lipid Peroxides; Male; Middle Aged; Myocardial Infarction; Oxidative Stress; Ventricular Function, Left; Vitamin A; Vitamin E; Vitamins

Experimental studies indicate that oxygen-free radicals contribute to ischemic myocardial damage and affect electric properties of cellular membranes. We hypothesize that an association exists between an oxygen-free radical-induced component of myocardial ischemic injury and altered electric function that underlies the genesis of ventricular late potentials in the course of myocardial infarction. If so, antioxidant vitamins C and E may prevent alterations in the signal-averaged electrocardiogram (SAECG). To test this hypothesis, we investigated the effect of supplementation with vitamins C and E on the indices of the SAECG in patients with acute myocardial infarction (AMI). Sixty-one patients with AMI were randomized to receive conventional treatment and vitamins C and E, each 600 mg/day, orally for 14 days (supplemented group, n = 33) or conventional treatment only (control group, n = 28). SAECG was recorded on days 1 or 2 and between days 9 and 13 (mean 10). Serum ascorbic acid, tocopherol, plasma lipid peroxides, and oxygen-free radical production by isolated leukocytes were measured on days 1 or 2 and between days 12 and 14. In the control group, SAECG showed an increase in mean QRS and low-amplitude ( < 40 microV) signal durations, from 99 +/- 10 to 111 +/- 13 ms (p < 0.001) and from 31 +/- 8 to 38 +/- 10 ms (p < 0.001), respectively, and a decrease in the root-mean-square voltage of the last 40 ms of the QRS complex, from 36 +/- 25 to 21 +/- 11 microV (p < 0.002). In vitamin-supplemented patients, all these indices remained unchanged. Oxygen-free radical production by isolated leukocytes was decreased compared with that in controls (p < 0.02). Supplementation was confirmed by elevation of serum ascorbic acid and tocopherol. Results support the hypothesis that in patients with AMI, oxygen-free radical-induced cellular damage contributes to alterations in electric function of the heart as seen on the SAECG.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Drug Therapy, Combination; Electrocardiography; Female; Free Radicals; Humans; Leukocytes; Lipid Peroxides; Luminescent Measurements; Male; Middle Aged; Myocardial Infarction; Reactive Oxygen Species; Signal Processing, Computer-Assisted; Vitamin E

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

To determine whether a fat- and energy-reduced diet rich in antioxidant vitamins C and E, beta carotene, and soluble dietary fiber reduces free-radical stress and cardiac enzyme level and increases plasma ascorbic acid level 1 week after acute myocardial infarction.. Randomized, single blind, controlled study.. Primary- and secondary-care research center for patients with myocardial infarction.. All subjects with suspected acute myocardial infarction (n = 505) were considered for entry to the study. Subjects with definite or possible acute myocardial infarction and unstable angina (according to World Health Organization criteria) were assigned to either an intervention diet (n = 204) or a control diet (n = 202) within 48 hours of symptoms of infarction.. Intervention and control groups were advised to consume a fat-reduced, oil-substituted diet. The intervention group was also advised to eat more fruits, vegetable soup, pulses, and crushed almonds and walnuts mixed with skim milk.. Reduction in plasma lipid peroxide and lactate dehydrogenase cardiac enzyme levels, increase in plasma ascorbic acid level, and compliance with diet, especially with vitamin C intake as determined by chemical analysis.. A two-sample t test using one-way analysis of variance for comparison of data.. Plasma lipid peroxide level decreased significantly in the intervention group compared with the control group (0.59 pmol/L in the intervention group and 0.10 pmol/L in the control group; 95% confidence interval of difference = 0.19 to 0.83). Lactate dehydrogenase level increased less in the intervention group than in the control group (427.7 vs 561.2 U/L; confidence interval of difference = 82.9 to 184.7). Plasma ascorbic acid level increased more in the intervention group than in the control group (23.38 vs 7.95 mumol/L; confidence interval of difference = 12.85 to 26.13).. Consumption of an antioxidant-rich diet may reduce the plasma levels of lipid peroxide and cardiac enzyme and increase the plasma level of ascorbic acid. Antioxidant-rich foods may reduce myocardial necrosis and reperfusion injury induced by oxygen free radicals.

Topics: Analysis of Variance; Ascorbic Acid; beta Carotene; Carotenoids; Diet, Fat-Restricted; Dietary Fiber; Female; Free Radicals; Humans; L-Lactate Dehydrogenase; Lipid Peroxides; Male; Myocardial Infarction; Single-Blind Method; Vitamin A; Vitamin E; Vitamins

The objective of the study was to evaluate the contribution of dietary factors to variation of plasma levels of lipids, apoproteins and lipoparticles in the Northern Ireland population. This study was part of a larger case-control study of the genetic and environmental determinants of myocardial infarction in France and Northern Ireland. A random sample of 175 middle aged men was drawn from the population covered by the Belfast MONICA project register. Habitual diet was assessed by a questionnaire. A blood sample was obtained after an over-night fast for determination of plasma levels of lipids, apoproteins and lipoparticles. All participants had a medical examination and completed a lifestyle questionnaire. In a stepwise regression, after adjusting for co-factors (i) vitamin C and (ii) alcohol consumption were the only nutrients which contributed significantly to the variation in, respectively, (i) Total Cholesterol, LDL Cholesterol and Apolipoprotein B (inverse correlation) and (ii) HDL Cholesterol and LpAI (positive correlation). The amount of variation explained by the final models was modest, ranging from 4% to 15%. In conclusion, in this Northern Ireland population, habitual diet contributes to little of the variation in plasma levels of lipids, apoproteins and lipoparticles.

Topics: Adult; Alcohol Drinking; Apoproteins; Ascorbic Acid; Case-Control Studies; Coronary Disease; Diet; Energy Intake; France; Humans; Life Style; Lipids; Male; Middle Aged; Myocardial Infarction; Northern Ireland; Risk Factors; Surveys and Questionnaires

Clinical studies suggest that neutrophil activation during acute myocardial infarction (MI) aggravates tissue injury. Activated neutrophils are an important source of oxygen free radicals (OFR), the injurious effects of which are counteracted by endogenous antioxidants. We have previously shown in healthy subjects that supplementation with antioxidant vitamins C and E suppresses OFR production by isolated neutrophils assayed by chemiluminescence (CL). The present study, performed in patients with acute MI aimed (1) to investigate the effect of vitamin C and E supplementation upon neutrophil OFR production and serum lipid peroxides, (2) to evaluate serum levels of vitamins C and E in the course of MI. Forty-five patients with acute MI were randomized to receive either conventional treatment only (control, n=22). All measurements were performed on the 1st and 14th day. Neutrophil OFR production assayed by CL decreased significantly in VIT patients (Wilcoxon test for paired data P<0.01, Chi square test P<0.01). In the control group, changes in OFR production were not significant. Serum lipid peroxides (measured as TBARS) increased in controls (P<0.05), but remained stable in VIT patients. Mean (+/-SE) serum ascorbic acid and tocopherol on the 1st day were 0.43 +/- 0.18% and 3.25 +/- 1.32 microM.M(-1) cholesterol, respectively, in all patients. On the 14th day in non-supplemented patients mean tocopherol was unchanged, whereas ascorbic acid increased significantly (0.63 +/- 0.24 mg%, P<0.01) suggesting that a low basal level was associated at least in part with the acute phase of the disease. An expected increase in serum vitamin levels occurred in VIT patients. In conclusion, supplementation with vitamins C and E suppresses neutrophil OFR production and lowers the marker of lipid peroxidation in patients with MI.

Topics: Adult; Aged; Ascorbic Acid; Female; Humans; Lipid Peroxidation; Lipid Peroxides; Luminescent Measurements; Male; Middle Aged; Myocardial Infarction; Neutrophils; Vitamin E

Forty patients with past history myocardial infarction were divided into three groups. Group I served as controls, while Groups II and III were given respectively, 1 g and 2 g vitamin C daily, divided in two doses. Samples were collected initially, and then every 2 months during the 6-month period of vitamin C administration and finally 2 months after stopping vitamin C. Vitamin C, 0.5 g twice daily (Group II), increased serum ascorbic acid by about 22% (P less than 0.05). However, no significant changes were observed in fibrinolytic activity or blood lipids. When the dose of vitamin C was doubled, serum ascorbic acid increased by about 96% and fibrinolytic activity increased by 45% (P less than 0.01), while the platelet adhesive index decreased by 27% (P less than 0.01). The serum cholesterol level dropped by 12% (P less than 0.05) and a significant decrease in serum beta lipoproteins and an increase in the alpha fraction was also seen. A further 40 patients with acute myocardial infarction were divided into two groups; one received 2 g vitamin C daily for the first 20 days and the other received a placebo. Blood samples were collected every 10th day during the 40-day follow up. Vitamin C administration increased fibrinolytic activity by 62.5%, while serum ascorbic acid rose by 94%.

Topics: Acute Disease; Adult; Arteriosclerosis; Ascorbic Acid; Coronary Disease; Fibrinolysis; Humans; Lipids; Male; Middle Aged; Myocardial Infarction; Platelet Adhesiveness; Time Factors

Extracellular collagen remodeling is one of the central mechanisms responsible for the structural and compositional coherence of myocardium in patients undergoing myocardial infarction (MI). Activated primary cardiac fibroblasts following myocardial infarction are extensively investigated to establish anti-fibrotic therapies to improve left ventricular remodeling. To systematically assess vitamin C functions as a potential modulator involved in collagen fibrillogenesis in an in vitro model mimicking heart tissue healing after MI. Mouse primary cardiac fibroblasts were isolated from wild-type C57BL/6 mice and cultured under normal and profibrotic (hypoxic + transforming growth factor beta 1) conditions on freshly prepared coatings mimicking extracellular matrix (ECM) remodeling during healing after an MI. At 10 μg/mL, vitamin C reprogramed the respiratory mitochondrial metabolism, which is effectively associated with a more increased accumulation of intracellular reactive oxygen species (iROS) than the number of those generated by mitochondrial reactive oxygen species (mROS). The mRNA/protein expression of subtypes I, III collagen, and fibroblasts differentiations markers were upregulated over time, particularly in the presence of vitamin C. The collagen substrate potentiated the modulator role of vitamin C in reinforcing the structure of types I and III collagen synthesis by reducing collagen V expression in a timely manner, which is important in the initiation of fibrillogenesis. Altogether, our study evidenced the synergistic function of vitamin C at an optimum dose on maintaining the equilibrium functionality of radical scavenger and gene transcription, which are important in the initial phases after healing after an MI, while modulating the synthesis of de novo collagen fibrils, which is important in the final stage of tissue healing.

Topics: Animals; Ascorbic Acid; Collagen; Fibroblasts; Mice; Mice, Inbred C57BL; Myocardial Infarction; Myocardium; Reactive Oxygen Species; Ventricular Remodeling; Vitamins

Topics: Ascorbic Acid; Biomarkers; Biosensing Techniques; Early Diagnosis; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Humans; Myocardial Infarction

Mature cardiomyocytes (CMs) obtained from human pluripotent stem cells (hPSCs) have been required for more accurate in vitro modeling of adult-onset cardiac disease and drug discovery. Here, we found that FGF4 and ascorbic acid (AA) induce differentiation of BG01 human embryonic stem cell-cardiogenic mesoderm cells (hESC-CMCs) into mature and ventricular CMs. Co-treatment of BG01 hESC-CMCs with FGF4+AA synergistically induced differentiation into mature and ventricular CMs. FGF4+AA-treated BG01 hESC-CMs robustly released acute myocardial infarction (AMI) biomarkers (cTnI, CK-MB, and myoglobin) into culture medium in response to hypoxic injury. Hypoxia-responsive genes and potential cardiac biomarkers proved in the diagnosis and prognosis of coronary artery diseases were induced in FGF4+AA-treated BG01 hESC-CMs in response to hypoxia based on transcriptome analyses. This study demonstrates that it is feasible to model hypoxic stress in vitro using hESC-CMs matured by soluble factors.

Topics: Ascorbic Acid; Biomarkers; Cell Differentiation; Cell Hypoxia; Cell Line; Culture Media; Fibroblast Growth Factor 4; Gene Expression Regulation; Heart Ventricles; Human Embryonic Stem Cells; Humans; Models, Biological; Myocardial Infarction; Myocytes, Cardiac; Stress, Physiological; Transcriptome

Fibroblasts can be directly reprogrammed into cardiomyocytes, endothelial cells or smooth muscle cells. Here we report the reprogramming of mouse tail-tip fibroblasts simultaneously into cells resembling these three cell types using the microRNA mimic miR-208b-3p, ascorbic acid and bone morphogenetic protein 4, as well as the formation of tissue-like structures formed by the directly reprogrammed cells. Implantation of the formed cardiovascular tissue into the infarcted hearts of mice led to the migration of reprogrammed cells to the injured tissue, reducing regional cardiac strain and improving cardiac function. The migrated endothelial cells and smooth muscle cells contributed to vessel formation, and the migrated cardiomyocytes, which initially displayed immature characteristics, became mature over time and formed gap junctions with host cardiomyocytes. Direct reprogramming of somatic cells to make cardiac tissue may aid the development of applications in cell therapy, disease modelling and drug discovery for cardiovascular diseases.

Topics: Animals; Ascorbic Acid; Bone Morphogenetic Protein 4; Cellular Reprogramming; Endothelial Cells; Fibroblasts; Gap Junctions; Heart; Mice; Mice, Inbred C57BL; MicroRNAs; Myocardial Infarction; Myocardium; Myocytes, Smooth Muscle; Myosin Heavy Chains; Neovascularization, Physiologic; Regeneration; Transcriptome

One of the major issues in cell therapy of myocardial infarction (MI) is early death of engrafted cells in a harsh oxidative stress environment, which limits the potential therapeutic utility of this strategy in the clinical setting. Increasing evidence implicates beneficial effects of omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and ascorbic acid (AA) in cardiovascular diseases, in particular their role in ameliorating fibrosis. In the current study, we aim to assess the cytoprotective role of EPA + DHA and AA in protecting embryonic stem cell (ESC)-derived cardiac lineage cells and amelioration of fibrosis. Herein, we have shown that preincubation of the cells with EPA + DHA + AA prior to H

Topics: Animals; Ascorbic Acid; Biomarkers; Blotting, Western; Cardiovascular Diseases; Cell Differentiation; Cell Survival; Docosahexaenoic Acids; Echocardiography; Eicosapentaenoic Acid; Embryonic Stem Cells; Fatty Acids, Omega-3; Heme Oxygenase-1; Humans; Hydrogen Peroxide; Male; Myocardial Infarction; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction

Patients with ST-segment elevation (STEMI) have totally occluded vessels, while patients with non-ST-segment elevation (NSTEMI) present partial vessel occlusion, which may generate different levels of Reactive Oxygen Species (ROS). Objectives: The aim of this study was to compare the oxidative profile in AMI patients with ST segment elevation and non-STEMI as well as control subjects.. This study was carried with 46 AMI patients divided into STEMI and NSTEMI. The control group consisted of 40 healthy subjects. Oxidative stress profile was evaluated analyzing carbonyl protein (PCO), lipid peroxidation (TBARS), ischemia-modified albumin (IMA), vitamin C (VIT C), superoxide dismutase (SOD) and catalase (CAT).. Serum PCO (p < 0.001), plasma TBARS (p < 0.01), serum IMA (p < 0.0001) levels, erythrocytes CAT (p < 0.001), and SOD activities (p < 0.05) were significantly higher in STEMI patients when compared with the control group (p < 0.001). No difference in the IMA levels and oxidative stress parameters was observed between conditions of AMI. Only plasma VIT C in STEMI patients was significantly lower when compared with NSTEMI patients and control group (p < 0.001).. Results suggest that the oxidative profile generated by STEMI and NSTEMI is similar regardless of the size of arterial occlusion generated by thrombus.

Topics: Ascorbic Acid; Catalase; Electrocardiography; Humans; Middle Aged; Myocardial Infarction; Oxidation-Reduction; Superoxide Dismutase

Oxidative stress has been implicated in the pathogenesis of heart failure (HF). However, data on the association between antioxidant intakes and circulating levels and risk of incident HF in the older general population are limited. We have examined prospectively the associations between plasma vitamin C and E, dietary intakes of vitamin C and E, and incident HF.. Prospective study of 3919 men aged 60 to 79 years with no prevalent HF followed up for a mean period of 11 years, in whom there were 263 cases with incident HF. Higher plasma vitamin C level was associated with significantly lower risk of incident HF in both men with and without previous myocardial infarction after adjustment for lifestyle characteristics, diabetes mellitus, blood lipids, blood pressure, and heart rate (hazards ratio [95% confidence interval], 0.81 [0.70, 0.93] and 0.75 [0.59, 0.97] for 1 SD increase in log vitamin C, respectively). Plasma vitamin E and dietary vitamin C intake showed no association with HF. High levels of dietary vitamin E intake (which correlated weakly with plasma vitamin E) were associated with increased risk of HF in men with no previous myocardial infarction even after adjustment (adjusted hazards ratio [95% confidence interval], 1.23 [1.06, 1.42] for 1 SD increase).. Higher plasma vitamin C is associated with a reduced risk of HF in older men with and without myocardial infarction. High intake of dietary vitamin E may be associated with increased HF risk. Primary intervention trials assessing the effect of vitamin C supplements on HF risk in the elderly are needed.

Topics: Aged; Ascorbic Acid; Diabetic Angiopathies; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Risk Assessment; Vitamin E

Cardiovascular disease (CVD) remains one of the major killers in modern society. One strong risk factor of CVD is cigarette smoking that causes myocardial injury and leads to the genesis of pathological cardiovascular events. However, the exact toxic component(s) of cigarette smoke (CS) and its molecular and cellular mechanisms for causing myocardial injury leading to heart damage and its prevention are largely unknown.. Using a guinea pig model, here we show that chronic exposure to CS produces myocardial injury that is prevented by vitamin C. Male guinea pigs were fed either vitamin C-deficient (0.5 mg/day) or vitamin C-sufficient (15 mg/day) diet and subjected to CS exposure from 5 Kentucky Research cigarettes (3R4F)/day (6 days/week) in a smoke chamber up to 8 weeks. Pair-fed sham controls were subjected to air exposure instead of CS exposure under similar conditions. Myocardial injury was produced in CS-exposed marginal vitamin C-deficient guinea pigs as evidenced by release of cardiac Troponin-T and I in the serum, oxidative stress, inflammation, apoptosis, thrombosis and collagen deposition in the myocardium. Treatment of rat cardiomyocyte cells (H9c2) in vitro and guinea pigs in vivo with p-benzoquinone (p-BQ) in amounts derived from CS revealed that p-BQ was a major factor responsible for CS-induced myocardial damage. A moderately large dose of vitamin C (15 mg/day) prevented CS/p-BQ-induced myocardial injury. Population based studies indicated that plasma vitamin C levels of smokers without disease were significantly lower (p = 0,0000) than that of non-smokers. Vitamin C levels of CS-related cardiovascular patients were further lower (p = 0.0000) than that of smokers without disease.. The results indicate that dietary supplementation of vitamin C may be a novel and simple therapy for the prevention of pathological cardiovascular events in habitual smokers.

Topics: Adult; Aged; Animals; Apoptosis; Ascorbic Acid; Benzoquinones; Disease Progression; Enzyme Activation; Guinea Pigs; Humans; Inflammation; Male; Matrix Metalloproteinases; Middle Aged; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Neutrophil Infiltration; Oxidative Stress; Rats; Smoking

Acute myocardial infarction (AMI) is a highly dynamic event, which is associated with increasing production of reactive oxygen species (ROS). The imbalance between ROS production and antioxidant defenses leads to the condition known as oxidative stress. The most widely recognized effect of increasing oxidative stress is the oxidation and damage of macromolecules, membranes, proteins, and DNA. Therefore, in this study we sought to evaluate oxidative stress and antioxidant defenses in patients with AMI. Lipid peroxidation, protein carbonyl levels, and enzymatic and nonenzymatic antioxidants were assessed in samples obtained from 40 AMI patients and 40 control patients. AMI was characterized by clinical, electrocardiographic, and laboratory criteria. The control group was divided into two groups of 20 patients: a control group with healthy patients and a risk group. Our results demonstrated an increase in substances reactive to thiobarbituric acid (TBARS) and carbonyl protein levels in the AMI and risk groups. In addition, a positive correlation was found between TBARS, carbonyl protein levels, and troponin I in AMI patients. Surprisingly, for the enzymatic antioxidant defenses, catalase and superoxide dismutase, we observed an increase in these parameters in the AMI and risk groups when compared with healthy patients. However, a decrease in nonenzymatic antioxidants such as vitamin C and vitamin E was observed in AMI patients when compared with the healthy group and the risk group. The increase in oxidative stress was probably a result of the elevation in ROS production due to the ischemic/reperfusion event that occurs in AMI, in addition to the decrease of nonenzymatic antioxidant defenses.

Topics: Adult; Antioxidants; Ascorbic Acid; Biomarkers; Brazil; Case-Control Studies; Catalase; Female; Humans; Lipid Peroxidation; Male; Middle Aged; Myocardial Infarction; Oxidative Stress; Protein Carbonylation; Reactive Oxygen Species; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Troponin I; Vitamin E

Myocardial infarction affects a large population in the world. Lipid peroxide metabolism plays an important role in the pathology of myocardial infarction. This study aims to evaluate the preventive effect of caffeic acid on lipid peroxides, antioxidants, cardiac marker enzymes, and histopathological findings in isoproterenol (ISO)-induced myocardial-infarcted male Wistar rats. Myocardial infarction was induced in rats by subcutaneous injection of ISO (100 mg/kg) at an interval of 24 hours for 2 days. The ISO-induced rats showed significant increase in the levels of thiobarbituric acid reactive substances, lipid hydroperoxides in the heart, plasma uric acid, and serum cardiac marker enzymes, and significant decrease in the activities of heart superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and the levels of reduced glutathione, vitamin E, and vitamin C in the plasma and heart. Oral pretreatment with caffeic acid (15 mg/kg) daily for 10 days showed significant decrease in the levels of serum cardiac marker enzymes, heart lipid peroxidation products and plasma uric acid and significant increase in the levels of antioxidant system. Histopathology of myocardium also confirmed the protective effect of caffeic acid in myocardial-infarcted rats. In vitro study on total antioxidant activity (2,2'-azinobis-[3-ethylbenzothiazoline-6-sulfonic acid](+) assay) confirmed the strong antioxidant action of caffeic acid. Thus, the present study revealed that caffeic acid ameliorates cardiac damage in ISO-induced myocardial infarction by maintaining lipid peroxide metabolism due to its free radical scavenging and antioxidant effects. A diet containing caffeic acid may be beneficial to myocardial infarction.

Topics: Animals; Ascorbic Acid; Biomarkers; Caffeic Acids; Isoproterenol; Lipid Peroxidation; Male; Myocardial Infarction; Myocardium; Rats; Rats, Wistar; Uric Acid; Vitamin E

This study was designed to investigate the cardioprotective effect of sesamol on isoproterenol (ISO)-induced myocardial infarction in adult male albino Wistar rats. The heart damage induced by ISO was indicated by elevated levels of the marker enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase-MB (CK-MB) and the levels of troponin T and I in the plasma. In addition, lipid peroxidative markers such as thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lipid hydroperoxides (LHP) significantly increased in the plasma and heart. Activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) significantly decreased in the heart and (non-enzymic antioxidants) vitamin C, vitamin E and reduced glutathione (GSH)) levels significantly decreased in the plasma and heart in ISO-rats. Histopathological observations correlated with the biochemical parameters. Administration of sesamol at different doses 50, 100 and 200 mg/kg body weight intraperitoneally for 7 days prevented the above changes and improved towards normality; the 50 mg dose was more effective than the other two doses.

Topics: Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Benzodioxoles; Creatine Kinase; Glutathione; Isoproterenol; L-Lactate Dehydrogenase; Lipid Peroxides; Male; Myocardial Infarction; Myocardium; Phenols; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Troponin I; Troponin T; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Humans; Myocardial Infarction; Vitamin B Complex; Vitamin E

Topics: Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Benzodioxoles; Creatine Kinase; Glutathione; Isoproterenol; L-Lactate Dehydrogenase; Lipid Peroxides; Male; Myocardial Infarction; Phenols; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Troponin I; Troponin T; Vitamin E

There is significant evidence that reactive oxygen species play an important role in endothelial dysfunction, ischemia/reperfusion injury as well as in the pathogenesis of diabetes mellitus (DM). It is also known that vitamins C and E have substantial antioxidant properties. However, clinical evidence concerning this topic is insufficient so far. The aim of the present study was to determine if the administration of vitamins C and E influences the outcome in diabetic patients with acute myocardial infarction (AMI).. Among 800 patients with AMI included in the MIVIT (Myocardial Infarction and Vitamins) study, 122 patients (15%) had confirmed DM. A retrospective analysis of the influence of vitamins C and E on 30-day cardiac mortality in patients with or without DM was performed.. There was a significant reduction in 30-day cardiac mortality in diabetic patients treated with antioxidant vitamins C and E [5 (8%) vs. 14 (22%); OR 0.32, 95% CI 0.11-0.93; p = 0.036]. Such an effect has not been observed in patients without DM [19 (6%) vs. 19 (6%); OR 0.97, 95% CI 0.51-1.85; p = 0.94].. The results suggest that early administration of antioxidant vitamins C and E in patients with AMI and concomitant DM reduces cardiac mortality.

Topics: Aged; Antioxidants; Ascorbic Acid; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Myocardial Infarction; Oxidative Stress; Pilot Projects; Randomized Controlled Trials as Topic; Reactive Oxygen Species; Retrospective Studies; Risk Factors; Treatment Outcome; Vitamin E

The goal of this study was to investigate whether sub-chronic anti-oxidant treatment with ascorbic acid (Vit C) is able to protect the heart against myocardial infarction. The effects of Vit C treatment on the histopatological changes and immunohistochemistry for p53, COX-2 and iNOS were evaluated in rats submitted to acute myocardial infarction induced by isoproterenol (ISO). Male Wistar rats (n = 32) were divided into four groups: group 1, control; group 2, ISO treated; group 3, Vit C treated; group 4, ISO + Vit C treated. An amount of 150 mg/kg of isoproterenol was administered for two consecutive days. The rats were treated with Vit C once a day (150 mg/kg, orally) for seven consecutive days. In the day 5 and 6 the rats from group ISO + Vit C were submitted to acute administration of ISO third minutes after Vit C treatment. The results pointed out that treatment with Vit C showed mild degenerative changes of myocardial tissue in ISO group. Also, the antioxidant was able to decrease the iNOS expression in rats treated with Vit C. Taken together, our results suggest that chronic Vit C administration was able to prevent the myocardial infarction induced by ISO as a result of iNOS downregulation. Certainly, this finding offers new insights into the mechanisms underlying the relation between oxidative stress and cardiac mortality after myocardial infarction.

Topics: Animals; Antioxidants; Ascorbic Acid; Cyclooxygenase 2; Immunohistochemistry; Isoproterenol; Male; Myocardial Infarction; Nitric Oxide Synthase Type II; Rats; Rats, Wistar; Tumor Suppressor Protein p53

In the present study, we tested whether or not acute antioxidant treatment with vitamin C is able to protect the heart during myocardial infarction. The effects of vitamin C on the autonomic balancing of the heart and on the histopathological and immunohistochemical changes in response to isoproterenol administration (ISO) were evaluated.. Four groups of male Wistar rats (n = 32) were studied: control; ISO treated; vitamin C treated; ISO + vitamin C treated. ISO 150 mg/kg was administered for 2 consecutive days. Vitamin C (250 mg/kg, oral) was administered 30 min before each ISO treatment. Phenylephrine and sodium nitroprusside were administrated to increase or decrease blood pressure in conscious rats.. The baroreceptor reflex index for bradycardia was significantly reduced in the ISO group (control, -3.4 +/- 0.3 beats/mm Hg; ISO -2 +/- 0.4 beats/mm Hg) and vitamin C treatment significantly improved the reflex index (-2.9 +/- 0.7 beats/mm Hg). Treatment with vitamin C showed mild degenerative changes in the myocardial tissue of the ISO group. The antioxidant was able to decrease the inducible nitric oxide (iNOS) expression in rats treated with vitamin C.. Vitamin C administration proved to be effective in reducing the extent of myocardial damage during ISO-induced myocardial infarction in rats associated with an iNOS downregulation and improving the autonomic balancing of the heart.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Cardiotonic Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Isoproterenol; Male; Myocardial Infarction; Myocardium; Nitric Oxide Synthase Type II; Nitroprusside; Phenylephrine; Rats; Rats, Wistar

Coronary heart disease and in particular its most serious form - acute myocardial infarction (AMI) - represents the most common cause of mortality in developed countries. Better prognosis may be achieved by understanding the etiopathogenetic mechanisms of AMI. Therefore, a catecholamine model of myocardial injury, which has appeared to be very similar to AMI in human in some aspect, was used. Male Wistar:Han rats were randomly divided into two groups: control group (saline) and isoprenaline group (ISO; synthetic catecholamine, 100 mg.kg(- 1) subcutaneously [s.c.]). After 24 hours, functional parameters were measured, biochemical markers in the blood and metals content in the heart tissue were analysed and histological examination was performed. ISO caused marked myocardial injury that was associated with myocardial calcium overload. Close correlation between myocardial impairment (i.e. serum TnT, stroke volume index and wet ventricles weight) and the levels of myocardial calcium was observed. Direct reactive oxygen species (ROS) involvement was documented only by non-significant increase in malonyldialdehyde 24 hours after ISO injury. Moreover, myocardial element analysis revealed no significant changes as for the content of zinc and iron while selenium and copper increased in the ISO group although it reached statistical significance only for the latter.

Topics: Animals; Antioxidants; Ascorbic Acid; Biomarkers; Blood Pressure; Calcium; Catecholamines; Disease Models, Animal; Heart Function Tests; Heart Rate; Heart Ventricles; Iron; Isoproterenol; Male; Myocardial Infarction; Myocardium; Organ Size; Rats; Rats, Wistar; Reactive Oxygen Species; Troponin T; Vitamin E; Zinc

Vitamin C is considered to be an antioxidant agent that is broadly used. Free radicals are involved in the protective mechanism of preconditioning (PC), but some antioxidant compounds abolish this benefit. The aim of the present study was to evaluate the effect of vitamin C on the protective effect of PC with respect to infarct size and oxidative stress in anesthetized rabbits. Male rabbits were randomly divided into six groups and subjected to 30 min of myocardial ischemia and 3h of reperfusion with the following interventions per group: (1) Control (no intervention), (2) Vit C 150 group (i.v. vitamin C at a total dose of 150 mg/kg for 75 min, starting 40 min before the onset of long ischemia and lasting up to the 5th min of reperfusion), (3) Vit C 300 group (i.v. vitamin C at a total dose of 300 mg/kg as previously described), (4) PC group (two cycles of 5 min ischemia and 10 min reperfusion), (5) combined PC-Vit C 150 group and (6) combined PC-Vit C 300 group. Blood samples were taken at different time points for malondialdehyde (MDA) assessment as a lipid peroxidation marker and for superoxide dismutase (SOD) activity. At the end of the experiment the infarct size was determined. Vitamin C, at both doses, did not reduce the infarct size (35.5+/-4.1%, 38.3+/-7.0% vs. 44.9+/-3.3% in the control group) and diminished the protection afforded by PC (32.0+/-2.7%, 43.8+/-3.3% vs. 15.7+/-2.9% in the PC group, P<0.05). At reperfusion there was an elevation of circulating MDA levels in the control and PC groups while in both vitamin C groups the levels were decreased. SOD activity was enhanced in the PC group compared to the controls; vitamin C did not change SOD activity during ischemia-reperfusion. Vitamin C abrogates the beneficial effect of ischemic PC on infarct size and elicits antioxidant properties during ischemia-reperfusion.

Topics: Animals; Ascorbic Acid; Ischemic Preconditioning, Myocardial; Lipid Peroxidation; Male; Malondialdehyde; Myocardial Infarction; Oxidative Stress; Rabbits; Superoxide Dismutase

Excessive oxidative stress is considered one of the mechanisms of a decrease in contractile force without concomitant reduction in oxygen cost in failing myocardium. We hypothesized that the antioxidant vitamin C may help reverse hyporesponsiveness to beta-adrenergic stimulation and improve myocardial efficiency in patients with heart failure (HF) after myocardial infarction (MI).. Nineteen patients with mild to moderate HF due to previous MI (mean left ventricular [LV] ejection fraction 39%) were instrumented with conductance and coronary sinus thermodilution catheters. Left ventricular contractility, expressed as E(es), the slope of end-systolic pressure-volume relationship, and mechanical efficiency, expressed as the ratio of LV stroke work (SW) to myocardial oxygen consumption (MVO2), were measured in response to the intravenous infusion of dobutamine (4 microg/kg per min) before (Dob) and during (Dob + Vit C) the infusion of vitamin C (2.0-g bolus injection and subsequent 50-mg/min infusion through the jugular vein) (vitamin C group, n = 10). The infusion of vitamin C augmented the E(es) response to dobutamine by 20% +/- 8% (Dob 2.1 +/- 0.3, Dob + Vit C 2.5 +/- 0.4 mm Hg/mL, P < .01) and the SW/MVO2 response by 21% +/- 5% (Dob 36% +/- 3%, Dob + Vit C 43% +/- 4%, P < .01). In the control group (n = 9), E(es) and SW/MVO2 were measured in response to dobutamine before (Dob) and during (Dob + vehicle) the infusion of saline. No difference in E(es) or SW/MVO2 was observed between Dob and Dob + vehicle (E(es): Dob 2.1 +/- 0.2, Dob + vehicle 2.1 +/- 0.2 mm Hg/mL per square meter, P = nonsignificant) (SW/MVO2: Dob 35% +/- 4%, Dob + vehicle 33% +/- 4%, P = nonsignificant).. The administration of the antioxidant vitamin C enhances the contractile response to dobutamine and improves myocardial efficiency in patients with HF.

Topics: Adrenergic beta-Agonists; Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Ascorbic Acid; Cardiac Catheterization; Cardiac Output; Cardiotonic Agents; Dobutamine; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Contraction; Myocardial Infarction; Reactive Oxygen Species; Thermodilution; Ventricular Function, Left

Studies on the lipid peroxidation and antioxidant changes and their significance during myocardial injury have provided a new insight into the pathogenesis of heart disease. The heart failure subsequent to myocardial infarction may be associated with an antioxidant deficit as well as increased myocardial oxidative stress. The present study was designed to evaluate the effect of the combination of ferulic acid and ascorbic acid on antioxidant defense system and lipid peroxidation against isoproterenol (ISO)-induced myocardial infarction in rats. Induction of rats with isoproterenol (150 mg/kg body weight daily, i.p.) for 2 days resulted in a marked elevation in lipid peroxidation, serum marker enzymes (LDH, CPK, GOT, and GPT), and a significant decrease in activities of endogenous antioxidants (SOD, GPx, GST, CAT, and GSH). Pre-co-treatment with the combination of ferulic acid (20 mg/kg body weight/day) and ascorbic acid (80 mg/kg body weight/day) orally for 6 days, significantly attenuated these changes when compared to the individual treatment groups. Histopathological observations were also in correlation with the biochemical parameters. Thus, ferulic acid and ascorbic acid significantly counteracted the pronounced oxidative stress effect of ISO by the inhibition of lipid peroxidation, restoration of antioxidant status, and myocardial marker enzymes levels. In conclusion, these findings indicate the synergistic protective effect of ferulic acid and ascorbic acid on lipid peroxidation and antioxidant defense system during ISO-induced myocardial infarction and associated oxidative stress in rats.

Topics: Animals; Antioxidants; Ascorbic Acid; Coumaric Acids; Drug Interactions; Drug Synergism; Free Radical Scavengers; Isoproterenol; Lipid Peroxidation; Male; Myocardial Infarction; Oxidative Stress; Oxidoreductases; Rats; Rats, Wistar

The present study aims at evaluating the effect of the combination of ferulic acid and ascorbic acid on isoproterenol-induced abnormalities in lipid metabolism. The rats were divided into eight groups: Control, isoproterenol, ferulic acid alone, ascorbic acid alone, ferulic acid+ascorbic acid, ferulic acid+isoproterenol, ascorbic acid+isoproterenol and ferulic acid+ascorbic acid+isoproterenol. Ferulic acid (20 mg/kg b.w.t.) and ascorbic acid (80 mg/kg b.w.t.) both alone and in combination was administered orally for 6 days and on the fifth and the sixth day, isoproterenol (150 mg/kg b.w.t.) was injected intraperitoneally to induce myocardial injury to rats. Induction of rats with isoproterenol resulted in a significant increase in the levels of triglycerides, total cholesterol, free fatty acids, free and ester cholesterol in both serum and cardiac tissue. A rise in the levels of phospholipids, lipid peroxides, low density lipoprotein and very low density lipoprotein-cholesterol was also observed in the serum of isoproterenol-intoxicated rats. Further, a decrease in the level of high density lipoprotein in serum and in the phospholipid levels, in the heart of isoproterenol-intoxicated rats was observed, which was paralleled by abnormal activities of lipid metabolizing enzymes: total lipase, cholesterol ester synthase, lipoprotein lipase and lecithin: cholesterol acyl transferase. Pre-cotreatment with the combination of ferulic acid and ascorbic acid significantly attenuated these alterations and restored the levels to near normal when compared to individual treatment groups. Histopathological observations were also in correlation with the biochemical parameters. These findings indicate the synergistic protective effect of ferulic acid and ascorbic acid on isoproterenol-induced abnormalities in lipid metabolism.

Topics: Adrenergic beta-Agonists; Animals; Antioxidants; Ascorbic Acid; Cardiotonic Agents; Coumaric Acids; Drug Combinations; Heart; Hypolipidemic Agents; Isoproterenol; Lipase; Lipid Metabolism; Lipid Peroxidation; Lipids; Male; Myocardial Infarction; Myocardium; Phosphatidylcholine-Sterol O-Acyltransferase; Rats; Rats, Wistar; Sterol Esterase

The consumption of diets rich in plant foods is associated with a reduced risk of cardiovascular diseases. This study aimed to evaluate the preventive role of rutin on lipid peroxides and antioxidants in normal and isoproterenol-induced myocardial infarction in rats. Subcutaneous injection of isoproterenol (150 mg kg(-1)) to male Wistar rats at an interval of 24 h for two days showed a significant increase in the activity of serum cardiac marker enzymes (creatine kinase, lactate dehydrogenase, aspartate transaminase and alanine transaminase) and a significant decrease in the activity of these enzymes in the heart. Lipid peroxidative products (thiobarbituricacid reactive substances and lipid hydroperoxides) were significantly increased and enzymic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymic (reduced glutathione and vitamin C) antioxidants showed a significant decrease in isoproterenol-treated rats. Pretreatment with rutin (40 or 80 mg kg(-1)) to isoproterenol-treated rats orally for a period of 42 days daily caused a significant effect. Administration of rutin to normal rats did not have any significant effect on any of the parameters studied. The results of our study show that rutin possesses antioxidant activity in isoproterenol-induced experimental myocardial infarction.

Topics: Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Catalase; Creatine Kinase, MB Form; Dose-Response Relationship, Drug; Glutathione; Glutathione Peroxidase; Heart; Isoproterenol; L-Lactate Dehydrogenase; Lipid Peroxides; Male; Myocardial Infarction; Myocardium; Rats; Rutin; Superoxide Dismutase

Oxidative stress plays an important role in mediating ventricular remodeling and dysfunction in heart failure (HF), but its mechanism of action has not been fully elucidated. In this study we determined whether a combination of antioxidant vitamins reduced myocyte apoptosis, beta-adrenergic receptor desensitization, and sarcoplasmic reticular (SR) Ca2+ ATPase downregulation in HF after myocardial infarction (MI) and whether these effects were associated with amelioration of left ventricular (LV) remodeling and dysfunction. Vitamins (vitamin C 300 mg and vitamin E 300 mg) were administered to rabbits 1 week after MI or sham operation for 11 weeks. The results showed that MI rabbits exhibited cardiac dilation and LV dysfunction measured by fractional shortening and the maximal rate of pressure rise (dP/dt), an index of contractility. These changes were associated with elevation of oxidative stress, decreases of mitochondrial Bcl-2 and cytochrome c proteins, increases of cytosolic Bax and cytochrome c proteins, caspase 9 and caspase 3 activities and myocyte apoptosis, and downregulation of beta-adrenergic receptor sensitivity and SR Ca2+ ATPase. Combined treatment with vitamins C and E diminished oxidative stress, increased mitochondrial Bcl-2 protein, decreased cytosolic Bax, prevented cytochrome c release from mitochondria to cytosol, reduced caspase 9 and caspase 3 activities and myocyte apoptosis, blocked beta-adrenergic receptor desensitization and SR Ca2+ ATPase downregulation, and attenuated LV dilation and dysfunction in HF after MI. The results suggest that antioxidant therapy may be beneficial in HF.

Topics: Animals; Apoptosis; Ascorbic Acid; Blotting, Western; Calcium-Transporting ATPases; Down-Regulation; Echocardiography; Heart Failure; Immunohistochemistry; In Situ Nick-End Labeling; Male; Mitochondria; Muscle Cells; Myocardial Infarction; Oxidative Stress; Rabbits; Receptors, Adrenergic, beta; Sarcoplasmic Reticulum; Ventricular Remodeling; Vitamin E; Vitamins

Altered membrane integrity has been suggested as a major factor in the development of cellular injury during myocardial necrosis. The present study was designed to investigate the effect of the combination of ferulic acid (FA) and ascorbic acid (AA) on lysosomal hydrolases and membrane-bound phosphatases during isoproterenol (ISO) induced myocardial necrosis in rats. Induction of rats with 1SO (150 mg/kg b.wt, i.p.) for 2 days resulted in a significant increase in the activities of lysosomal hydrolases (beta-D-glucuronidase, beta-D-galactosidase, beta-D-N-acetylglucosaminidase, acid phosphatase and cathepsin-D) in the heart and serum. A significant increase in plasma lactate level, cardiac levels of sodium, calcium and a decrease in cardiac level of potassium was also observed, which was paralleled by abnormal activities of membrane-bound phosphatases (Na(+)-K(+) ATPase, Ca(2+) ATPase and Mg(2+) ATPase) in the heart of ISO-administered rats. Pre-co-treatment with the combination of FA (20 mg/kg b.wt) and AA (80 mg/kg b.wt) orally for 6 days significantly attenuated these abnormalities and restored the levels to near normalcy when compared to individual drug treated groups. The combination of FA and AA preserved the membrane integrity by mitigating the oxidative stress and associated cellular damage more effectively when compared to individual treatment groups. In our study, the protection conferred by FA and AA might be through the nitric oxide pathway and by their ability of quenching free radicals. In conclusion, these findings indicate the synergistic modulation of lysosomal hydrolases and membrane phosphatases by the combination of FA and AA.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Ascorbic Acid; Cardiotonic Agents; Cell Membrane; Coumaric Acids; Drug Synergism; Free Radicals; Isoproterenol; Lysosomes; Male; Myocardial Infarction; Myocardium; Necrosis; Nitric Oxide; Oxidative Stress; Phosphoric Monoester Hydrolases; Rats; Rats, Wistar

This study was designed to evaluate the cardioprotective potential of naringin on lipid peroxides, enzymatic and nonenzymatic antioxidants and histopathological findings in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (85 mg/kg) to male Wistar rats showed a significant increase in the levels of thiobarbituric acid reactive substances and lipid hydroperoxides in plasma and the heart and a significant decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in the heart and the levels of reduced glutathione, vitamin C and vitamin E in plasma and heart and ceruloplasmin in plasma. Oral administration of naringin (10, 20 and 40 mg/kg, respectively) to ISO-induced rats daily for a period of 56 days showed a significant decrease in the levels of lipid peroxidative products and improved the antioxidant status by increasing the activities of antioxidant enzymes and nonenzymatic antioxidants. Histopathological findings of the myocardial tissue showed the protective role of naringin in ISO-induced rats. The effect at a dose of 40 mg/kg of naringin was more pronounced than that of the other two doses, 10 and 20mg/kg. The results of our study show that naringin possess anti-lipoperoxidative and antioxidant activity in experimentally induced cardiac toxicity.

Topics: Adrenergic beta-Agonists; Animals; Antioxidants; Ascorbic Acid; Ceruloplasmin; Enzymes; Flavanones; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Heart Diseases; Hydrogen Peroxide; Isoproterenol; Lipid Metabolism; Lipid Peroxides; Lipoproteins; Male; Muscle Fibers, Skeletal; Myocardial Infarction; Myocardium; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Antioxidant activity of ethanolic extract of fruits of Terminalia chebula (500 mg/kg body wt, orally for 30 days) against isoproterenol-induced oxidative stress was investigated in rats. The levels of serum lipid peroxides, iron, ascorbic acid, vitamin E, plasma iron-binding capacity, and the activities of ceruloplasmin and glutathione were assayed, in addition to the activities of the antioxidant enzymes--glutathione peroxidase, glutathione reductase, glutathione-S-transferase, superoxide dismutase and catalase in the heart tissue. Administration of isoproterenol increased the levels of lipid peroxides and iron, with corresponding decrease in the activities of the enzymic and non-enzymic antioxidants. The pre-treatment with ethanolic extract of fruits significantly prevented the alterations induced by isoproterenol, and maintained a near normal antioxidant status. Results suggest that the cardioprotective effect of T. chebula fruit may partly be attributed to its antioxidant properties.

Topics: Animals; Antioxidants; Ascorbic Acid; Ceruloplasmin; Ethanol; Fruit; Glutathione; Heart; Iron; Isoproterenol; Lipid Peroxidation; Male; Myocardial Infarction; Oxidation-Reduction; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Terminalia; Vitamin E

Serum levels of vitamin E (VE), beta-carotene (BC) and vitamin C (VC) were determined in 50 patients with the first acute myocardial infarction (AMI) before starting thrombolytical treatment. VE and BC were determined by HPLC, VC spectrophotometrically. The reperfused patients were divided according to vitamin concentrations into four groups. The lowest quartile was compared with the rest of the studied population (VE: group with high (H)>15.6 microM>group with low (L), BC: H>0.07 microM>L, VC: H>25 microM>L) in the following parameters: extent of myocardial damage (area under the curves of troponin I, CK-MB during 48 h), arrhythmia and congestive heart failure occurrence, size of ejection fraction, positivity of ventricular late potentials. No significant differences between groups H and L for either VE, BC or VC were found (P 0.05). As no correlation between serum concentrations of vitamins E, C and beta-carotene and the extent and clinical course of AMI was found, the actual vitamin concentrations may be important for prevention of ischemic heart a disease, but they do not play a decisive role in the acute phase of myocardial infarction in humans.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Female; Humans; Male; Middle Aged; Myocardial Infarction; Vitamin E; Vitamins

The effect of reperfusion of patients with myocardial infarction on the levels of some anti-oxidant enzymes, total thiols, malondialdehyde formation in erythrocytes and plasma ascorbate levels have been investigated. Significantly decreased activities of catalase and superoxide dismutase and decreased levels of total thiols in RBC's and ascorbic acid in plasma suggest that reperfusion of the infarcted myocardium leads to oxidative stress conditions wherein anti-oxidant mechanisms become less effective in coping with the oxidative insult. This view is further supported by the observation that in the post reperfused patients there is a highly significant enhancement in the levels of malondialdehyde.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Catalase; Erythrocytes; Female; Humans; Male; Malondialdehyde; Middle Aged; Myocardial Infarction; Myocardial Reperfusion Injury; Oxidative Stress; Sulfhydryl Compounds; Superoxide Dismutase

To compare plasma concentration of alpha-tocopherol and ascorbic acid in healthy seniors (age over 65 years), senior patients with either diabetes mellitus, acute myocardial infarction or dyslipidemia and recommended values of these vitamins.. Studied groups included 30 patients with diabetes mellitus (DM); 30 patients 1 - 2 weeks after acute myocardial infarction (AMI); 11 patients with lipid metabolism disorder (LD, total cholesterol > 6.2 mM); and control group of 27 healthy persons.. Concentration of alpha-tocopherol in DM group was 14.6 +/- 5.3 microM, in AMI group 13.7 +/- 5.6 microM, in LD group 15.9 +/- 5.6 microM and in control group 12.9 +/- 4.1 microM. No statistically significant differences were found. However, comparison of determined values with levels recommended for prevention revealed remarkable low plasma concentration of alpha-tocopherol in the Czech population. Plasma concentration of ascorbic acid in DM group was 47.07 +/- 22.80 microM, in AMI group 33.15 +/- 12.81 microM, in LD group 45.59 +/- 23.02 microM and in control group 43.28 +/- 26.57 microM. No statistically significant differences were found between the controls and individual groups of patients. Plasma concentrations of vitamin C reached the recommended value in all cases except the AMI group, where it was significantly lower.. Seniors in the Czech population were proved to be significantly short of alpha-tocopherol, minor shortage of vitamin C was found only in group of patients with myocardial infarction.

Topics: Aged; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Chromatography, High Pressure Liquid; Diabetes Mellitus; Female; Humans; Hyperlipidemias; Male; Myocardial Infarction

No-reflow phenomenon is observed in approximately one-third of patients after percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), and is associated with poor functional and clinical outcomes. On the other hand, the formation of free radicals in vasculature exerts deleterious effects on coronary microcirculation.. We hypothesized that redox state in coronary circulation may play a crucial role in no-reflow phenomenon in AMI.. Consecutive 26 patients with first AMI who underwent primary PCI < 24 h after onset were enrolled. Before PCI, blood samples were obtained from coronary sinus to measure plasma or serum antioxidative vitamins (vitamin C, vitamin E, and beta-carotene) and antioxidative enzymes (extracellular glutathione peroxidase [GPX], superoxide dismutase, and catalase). After PCI, the corrected Thrombolysis In Myocardial Infarction (TIMI) frame count (CTFC) was measured in the target vessel. Patients with TIMI < or = 2 flow despite an optimal PCI result were designated as no-reflow group (Group NR, n = 6) and the others as reflow group (Group R, n = 20).. Levels of vitamin C, vitamin E, and GPX before PCI were significantly lower in Group NR than in Group R. The CTFC correlated inversely with levels of vitamin C, vitamin E, and GPX (p < 0.05).. Depletion of antioxidants is associated with no-reflow phenomenon in AMI. These findings strongly suggest that the redox state in coronary circulation plays an important role in the pathogenesis of no-reflow phenomenon.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Catalase; Coronary Circulation; Female; Glutathione Peroxidase; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Oxidation-Reduction; Statistics, Nonparametric; Superoxide Dismutase; Vitamin E

Lipid peroxidation and derived oxidized products are being intensively investigated because of their potential to cause injury and because of their pathogenic role in several diseases. The view that an excess of lipid peroxidation products is present and is relevant in the pathogenesis of cardiogenic shock-induced damage has still not received definitive support.. To evaluate the extent of lipid peroxidation, the status of enzymatic and nonenzymatic antioxidants in patients with cardiogenic shock that complicate acute myocardial infarction (AMI) and to compare with normal subjects.. Compared with normal subjects, cardiogenic shock patients had higher malondialdehyde, conjugated dienes and reduced activities of erythrocyte antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and lower concentrations of reduced glutathione (GSH) in erythrocyte and in plasma GSH, vitamin C, vitamin E and in beta-carotene.. Cardiogenic shock is associated with greater than normal lipid peroxidation and with an imbalance in antioxidants' status. These results indicate that low activities of SOD, CAT, GPx and low concentrations of GSH, vitamin C, vitamin E and beta-carotene in the circulation of patients with cardiogenic shock complicating AMI may be due to increased utilization to scavenge lipid peroxides. Decrease in plasma concentrations of GSH, vitamin E and beta-carotene seems to be responsible for the elevation of lipid peroxidation in cardiogenic shock complicating AMI compared with MI.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Blood Pressure; Catalase; Female; Glutathione; Glutathione Peroxidase; Heart Rate; Humans; Male; Middle Aged; Myocardial Infarction; Oxidative Stress; Shock, Cardiogenic; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E

Free oxyradicals are involved in the signal transduction of ischemic preconditioning in rats and rabbits. Data from larger mammals in which the infarct development is closer to that in humans are lacking. We have therefore investigated the impact of the radical scavenger ascorbic acid on ischemic preconditioning in pigs. In 33 anesthetized pigs, the left anterior descending coronary artery was perfused from an extracorporeal circuit. Infarct size (measured as percent area at risk) was determined by triphenyltetrazolium chloride staining. In placebo-treated animals undergoing 90 min of severe ischemia and 120 min of reperfusion, infarct size averaged 26.9 +/- 3.9% (mean +/- SE; n = 9). Ischemic preconditioning by 10 min of ischemia and 15 min of reperfusion reduced infarct size to 6.4 +/- 2.4% (P < 0.05 vs. placebo; n = 9). Intravenous infusion of ascorbic acid (30 min before ischemic preconditioning or ischemia; 2-g bolus followed by 25 mg/min until the end of ischemia) had no effect on infarct size per se (22.6 +/- 6.5%; n = 6), but largely abolished the infarct size reduction by ischemic preconditioning (19.1 +/- 5.4%; n = 9). Scavenging of free oxyradicals with ascorbic acid largely attenuates the beneficial effect of ischemic preconditioning in pigs.

Topics: Animals; Antioxidants; Ascorbic Acid; Drug Administration Schedule; Female; Infusions, Intravenous; Ischemic Preconditioning, Myocardial; Male; Myocardial Infarction; Reactive Oxygen Species; Swine; Swine, Miniature

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Dietary Supplements; Glutathione; Humans; Malondialdehyde; Middle Aged; Myocardial Infarction

In a model of the high blood viscosity syndrome, developed after myocardial infarction in rats, it was observed that a therapy of a combination of diquertin (20 mg/kg) and ascorbic acid (50 mg/kg) for a -period of 6 days, resulted in an improvement of haemorheological indices. The decrease in blood -viscosity was primarily due to an improved deformability of erythrocytes, and to some extent, due to a decrease in the content of plasma fibrinogen and erythrocyte aggregation.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Viscosity; Disease Models, Animal; Drug Administration Schedule; Drug Therapy, Combination; Erythrocyte Aggregation; Fibrinogen; Male; Myocardial Infarction; Phytotherapy; Quercetin; Rats; Rats, Wistar

Epidemiological data on the relationship between vitamin C intake and ischemic heart disease (IHD) risk are limited in the Asian population, with a high prevalence of smoking. This study aims to investigate the association between vitamin C intake and the incidence of non-fatal IHD in Korean men.. The case group consisted of 108 patients with electrocardiogram-confirmed myocardial infarction or angiographically confirmed (>or=50% stenosis) coronary artery disease (CAD) who were admitted to a university teaching hospital in Seoul, Korea. The controls were 142 age-matched patients admitted to the departments of ophthalmology and orthopedic surgery at the same hospital. Vitamin C intake was assessed by a nutritionist using a semi-quantitative food frequency method, and body mass index (BMI), tobacco use and past history of cardiovascular disease were determined by examination and interview.. After controlling for cardiovascular risk factors, including BMI, smoking, past history of hypertension, past history of hyperlipidemia, dietary intakes of energy, total fat (or subtype of fat), cholesterol, beta-carotene, and vitamin E, the odds ratio (OR) of non-fatal IHD was 0.34 (95% confidence interval (CI) 0.13-0.90) in the highest tertile of vitamin C intake compared with those in the lowest tertile. In a subgroup analysis, which compared nonsmokers in the highest tertile of vitamin C intake to current smokers in the lowest tertile of vitamin C intake, the odds ratio of developing non-fatal IHD was 0.12 (95% CI 0.02-0.77).. This study suggests that higher intake of vitamin C is associated with the decreased risk of non-fatal IHD in a population with a high prevalence of smoking.

Topics: Antioxidants; Ascorbic Acid; Case-Control Studies; Confidence Intervals; Feeding Behavior; Humans; Korea; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Ischemia; Odds Ratio; Prevalence; Risk Factors; Smoking; Surveys and Questionnaires

We prospectively evaluated the relationship between dietary fiber and peripheral arterial disease risk (PAD) among 46,032 men, aged 40 to 75 y, in 1986. Subjects answered a vascular disease questionnaire and completed a validated 131-item food frequency questionnaire, and were free of PAD, cardiovascular disease and diabetes. During 12 y of follow-up 308 incident PAD cases were documented. After adjusting for age, smoking, hypertension, hypercholesterolemia, family history of early coronary heart disease, alcohol consumption, BMI, physical activity and energy intake, PAD risk in each quintile of cereal fiber intake compared with the lowest quintile was 0.69, 95% CI 0.49-0.97 for quintile 2; 0.65, 95% CI 0.45-0.94 for quintile 3; 0.68, 95% CI 0.47-0.98 for quintile 4; and 0.67, 95% CI 0.47-0.97 for quintile 5. In a nonlinear model the overall inverse association (P = 0.02) and nonlinear components (P = 0.03) were significant. Fruit, vegetable and total fiber intakes were not associated with PAD risk. These results suggest an inverse association between cereal fiber intake and PAD risk in men. Increasing cereal fiber intake may prevent PAD.

Topics: Adult; Aged; Arterial Occlusive Diseases; Ascorbic Acid; Body Mass Index; Boston; Dietary Fiber; Dietary Supplements; Feeding Behavior; Humans; Male; Middle Aged; Myocardial Infarction; Patient Selection; Reproducibility of Results; Risk Factors; Smoking; Surveys and Questionnaires; Vitamin E

Topics: Animals; Arteriosclerosis; Ascorbic Acid; Collagen; Disease Models, Animal; Disease Progression; Extracellular Matrix; Humans; Mice; Myocardial Infarction; Protein Processing, Post-Translational; Scurvy

To assess whether systemic oxidative stress can predict the risk of first myocardial infarction, ischemic stroke, and congestive heart failure.. A longitudinal study started in 1992 and completed in 1997.. Community-based, outpatient.. 102 apparently healthy, community-dwelling subjects age 80 and older from the Vibrata valley, Teramo, Italy.. Plasma vitamin E, beta-carotene, vitamin C, fluorescent products of lipid peroxidation (FPLPs), and serum lipids were determined at enrollment.. Thirty-two cardiovascular events were recorded in 47.4 months of follow-up. The subjects with vitamin E levels in the highest quartile had a risk of cardiovascular events one-sixth those with vitamin E levels in the lowest quartile (relative risk (RR) = 0.16; 95% confidence interval (CI) = 0.04-0.55). The subjects with FPLPs in the highest quartile had a risk seven times greater than those with FPLPs in the lowest quartile (RR = 7.61; 95% CI = 2.23-25.96). No association was observed for vitamin C, beta-carotene, or total cholesterol. Multivariate adjustment for known risk factors did not significantly change the results.. Our results suggest that in apparently healthy, community-dwelling very old subjects, base-line plasma concentration of vitamin E and FPLPs predicts the risk of future cardiovascular events. We confirm previous data showing that total cholesterol is not a predictor of cardiovascular disease in people age 80 and older.

Topics: Age Distribution; Age Factors; Aged; Aged, 80 and over; Ascorbic Acid; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Heart Failure; Humans; Incidence; Italy; Lipid Peroxides; Longitudinal Studies; Male; Multivariate Analysis; Myocardial Infarction; Oxidative Stress; Predictive Value of Tests; Risk Factors; Stroke; Triglycerides; Vitamin E

Glutathione S-transferase genotypes GSTT1, GSTM1, GSTP1 were characterised in 155 middle-aged men and compared with parameters of oxidative stress at the level of DNA and lipids, with antioxidant enzymes, and with plasma antioxidants in smokers and non-smokers. Smokers had on average significantly lower levels of Vitamin C, beta-carotene and beta-cryptoxanthin and higher amounts of oxidised purines and pyrimidines in lymphocyte DNA. The GSTM1 null genotype was associated with elevated glutathione as well as with higher Vitamin C concentration in plasma. Vitamin C was higher in GSTT1+ compared with GSTT1 null--as was glucose-6-phosphate dehydrogenase activity. The homozygous GSTP1 a/a genotype was associated with significantly higher levels of GST activity measured in lymphocytes, in comparison with the b/b genotype. Using multifactorial statistical analysis we found significant associations between smoking, GSTP1 genotype, plasma Vitamin C, and purine base damage in lymphocyte DNA. The difference in Vitamin C plasma levels between smokers and non-smokers was seen only with the GSTP1 b/b genotype. This group accounted also for most of the increase in purine oxidation in smokers. In contrast, the link between smoking and oxidised pyrimidines in DNA was seen only in the GSTT1 null group. It seems that polymorphisms in the phase II metabolising enzyme glutathione S-transferase may be important determinants of commonly measured biomarkers.

Topics: Analysis of Variance; Antioxidants; Ascorbic Acid; Case-Control Studies; DNA Damage; Glutathione; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Isoenzymes; Male; Middle Aged; Myocardial Infarction; Oxidative Stress; Polymorphism, Genetic; Pyrimidines; Rural Health; Smoking

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Myocardial Infarction

Low-fat soluble-antioxidant status is associated with an increased risk of heart disease.. The aim of this study was to examine whether low plasma concentrations of vitamin C confer an independent risk of acute myocardial infarction (AMI).. Male patients (n = 180) aged <65 y with a first AMI and without an existing diagnosis of angina (>6 mo) who were admitted within 12 h after onset of symptoms were compared with apparently healthy volunteers (n = 177). Plasma concentrations and dietary intakes of vitamin C were determined during hospitalization and 3 mo later.. Compared with the control subjects, the patients had higher total cholesterol and lower HDL-cholesterol concentrations and more of them smoked. The relative risk of AMI for the lowest compared with the highest quintile of plasma vitamin C during hospitalization (14.5 and >60.5 micromol/L, respectively) was 8.37 (95% CI: 3.28, 21. 4) after adjustment for classic risk factors. At 3 mo, mean (+/-SEM) plasma vitamin C concentrations in patients had increased significantly, from 19.6 +/- 1.2 to 35.1 +/- 1.9 micromol/L (P < 0. 001) and no longer conferred a risk of AMI [relative risk: 1.02 (95% CI: 0.51, 2.03)]. Habitual dietary vitamin C intake of patients (before AMI) did not differ significantly from that of control subjects. The increase in plasma vitamin C after recovery from the infarction could not be explained by a similarly large increase in dietary vitamin C.. A low plasma concentration of vitamin C was not associated with an increased risk of AMI, irrespective of smoking status. The apparent risk of AMI due to a low plasma vitamin C concentration was distorted by the acute phase response.

Topics: Adult; Ascorbic Acid; Blood Pressure; Cholesterol; Cholesterol, HDL; Cohort Studies; Humans; Male; Middle Aged; Myocardial Infarction; Risk Factors; Scotland; Smoking; Social Class; Surveys and Questionnaires; Triglycerides

Epidemiologic studies have shown dietary antioxidants to be inversely correlated with ischemic heart disease.. We investigated whether dietary beta-carotene, vitamin C, and vitamin E were related to the risk of myocardial infarction (MI) in an elderly population.. The study sample consisted of 4802 participants of the Rotterdam Study aged 55-95 y who were free of MI at baseline and for whom dietary data assessed by a semiquantitative food frequency questionnaire were available. During a 4-y follow-up period, 124 subjects had an MI. The association between energy-adjusted beta-carotene, vitamin C, and vitamin E intakes and risk of MI was examined by multivariate logistic regression.. Risk of MI for the highest compared with the lowest tertile of beta-carotene intake was 0.55 (95% CI: 0.34, 0.83; P for trend = 0.013), adjusted for age, sex, body mass index, pack-years, income, education, alcohol intake, energy-adjusted intakes of vitamin C and E, and use of antioxidative vitamin supplements. When beta-carotene intakes from supplements were considered, the inverse relation with risk of MI was slightly more pronounced. Stratification by smoking status indicated that the association was most evident in current and former smokers. No association with risk of MI was observed for dietary vitamin C and vitamin E.. The results of this observational study in the elderly population of the Rotterdam Study support the hypothesis that high dietary beta-carotene intakes may protect against cardiovascular disease. We did not observe an association between vitamin C or vitamin E and MI.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Diet; Female; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Regression Analysis; Risk Factors; Smoking; Surveys and Questionnaires; Vitamin E

Topics: Angiotensin-Converting Enzyme Inhibitors; Ascorbic Acid; Drug Therapy, Combination; Drug Tolerance; Hemodynamics; Humans; Myocardial Infarction; Nitroglycerin

This study sought to investigate the relations between plasma antioxidant status, extent of atherosclerosis and activity of coronary artery disease.. Previous studies indicate that increased antioxidant intake is associated with decreased coronary disease risk, but the underlying mechanisms remain controversial.. Plasma samples were obtained from 149 patients undergoing cardiac catheterization (65 with stable angina, 84 with unstable angina or a myocardial infarction within 2 weeks). Twelve plasma antioxidant/oxidant markers were measured and correlated with the extent of atherosclerosis and the presence of an unstable coronary syndrome.. By multiple linear regression analysis, age (p < 0.001), diabetes mellitus (p < 0.001), male gender (p < 0.001) and hypercholesterolemia (p = 0.02) were independent predictors of the extent of atherosclerosis. No antioxidant/oxidant marker correlated with the extent of atherosclerosis. However, lower plasma ascorbic acid concentration predicted the presence of an unstable coronary syndrome by multiple logistic regression (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.40 to 0.89, p = 0.01). The severity of atherosclerosis also predicted the presence of an unstable coronary syndrome (OR 1.7, 95% CI 1.14 to 2.47, p = 0.008) when all patients were considered. When only patients with significant coronary disease were considered (at least one stenosis >50%), ascorbic acid concentration (OR 0.56, 95% CI 0.37 to 0.85, p = 0.008) and total plasma thiols (OR 0.52, 95% CI 0.34 to 0.80, p = 0.004) predicted the presence of an unstable coronary syndrome, whereas the extent of atherosclerosis did not.. These data are consistent with the hypothesis that the beneficial effects of antioxidants in coronary artery disease may result, in part, by an influence on lesion activity rather than a reduction in the overall extent of fixed disease.

Topics: Aged; Angina Pectoris; Angina, Unstable; Antioxidants; Arteriosclerosis; Ascorbic Acid; Biomarkers; Coronary Disease; Female; Humans; Linear Models; Lipid Peroxidation; Logistic Models; Male; Middle Aged; Myocardial Infarction

1. The ability of EPC-K1 to improve myocardial infarction was evaluated in a rat model with coronary artery occlusion and reperfusion. 2. The myocardial infarct size was 30.5 +/- 1.7% by intravenous (i.v.) administration and 28.8 +/- 2.7% by intraduodenal (i.d.) administration of the saline EPC-K1 at doses between 1 and 10 mg/kg, i.v. and at doses between 50 and 200 mg/kg, i.d., reduced myocardial infarct size dose dependently. Significant reduction in myocardial infarct size was found at a dose of 10 mg/kg, i.v., and 200 mg/kg, i.d.

Topics: Animals; Antioxidants; Arterial Occlusive Diseases; Ascorbic Acid; Combined Modality Therapy; Coronary Disease; Disease Models, Animal; Free Radical Scavengers; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Rats; Rats, Wistar; Vitamin E

This study demonstrated that magnesium (Mg) reduces free radicals after a brief coronary occlusion-reperfusion sequence.. Magnesium has been shown to reduce infarct size in patients with acute myocardial infarction. We hypothesized that this action of Mg occurs through its action on free radicals.. Eighteen mongrel dogs were studied (nine control, nine receiving Mg). Catheters were placed into the coronary sinus for continuous blood withdrawal. A Varian E-4 electron paramagnetic resonance spectrometer was used to monitor the ascorbate free radical (AFR) signal in the coronary sinus blood; AFR is a measure of total oxidative stress. Occlusion of the left anterior descending coronary artery for 20 min was followed by reperfusion. The study animals received 4 g Mg intravenously starting at 15 min of occlusion (5 min before reperfusion) and continuing during reperfusion.. Results are presented as percent change from baseline +/- SEM. Magnesium blunted the peak AFR increase: at 4 min of reperfusion there was a 4.7 +/- 3.3% increase in AFR signal in the dogs receiving Mg versus an 18.2 +/- 3.3% increase in the control animals (p < 0.05). Total radical flux was reduced during reperfusion by 53% in the Mg dogs compared with controls (p < 0.05).. Magnesium attenuates AFR increase after an occlusion-reperfusion sequence. To our knowledge this is the first in vivo real-time demonstration of Mg's impact on free radicals.

Topics: Animals; Ascorbic Acid; Cardiac Catheterization; Coronary Disease; Coronary Vessels; Dogs; Electron Spin Resonance Spectroscopy; Free Radical Scavengers; Free Radicals; Infusions, Intravenous; Magnesium; Myocardial Infarction; Myocardial Reperfusion; Oxidative Stress

The activity of glutathione peroxidase (GSH-Px) as well as the activities of other antioxidative enzymes such as CuZn superoxide dismutase (CuZn SOD), catalase (CAT), glutathione reductase (GR) in erythrocytes, the plasma activity of glutathione-S-transferase (GST), and the plasma levels of vitamin E and vitamin C were evaluated in nine patients with acute myocardial infarction (AMI). Blood samples were taken before and 1, 3, 6, and 24 hours after the institution of thrombolytic therapy. The results were compared with those in 30 healthy volunteers. A significant decrease in catalase (CAT) activity and vitamin E content in patients before and after thrombolytic therapy as compared with controls was recorded. Our results confirmed that a disturbed oxidative/antioxidative balance is present after AMI and after thrombolytic therapy.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Catalase; Erythrocytes; Glutathione Peroxidase; Glutathione Reductase; Humans; Middle Aged; Myocardial Infarction; Myocardial Reperfusion Injury; Superoxide Dismutase; Thrombolytic Therapy; Vitamin E

Ischaemic heart disease is an emerging public health problem in Sri Lanka. Implementation of programs for lifetime control and prevention of established coronary risk factors such as smoking, hyperlipidaemia, hypertension, diabetes and hereditary risk are costly and unaffordable in countries such as Sri Lanka with limited resources for health care. Other potential risk factors which are less expensive with regard to prevention require investigation. This paper summarises several studies done over the past decade at Peradeniya, to investigate three such potential coronary risk factors of IHD, namely homocysteine, vitamin C and dietary fat.

Topics: Adult; Aged; Ascorbic Acid; Diet; Homocysteine; Humans; Lipids; Middle Aged; Myocardial Infarction; Risk Factors; Sri Lanka

Topics: Animals; Antioxidants; Ascorbic Acid; Dose-Response Relationship, Drug; Drug Interactions; Humans; Myocardial Infarction; Vitamin A; Vitamin E

The authors' study show that intravenous He-Ne laser therapy (HNLT) in patients with stable angina of effort (functional class II-III) and postinfarction cardiosclerosis irrespective of ejection fraction increased plasma katalase and red cell vitamin A concentrations. HNLT aroused vitamin E concentration in red cells in anginal patients with intact ejection fraction whereas in those with reduced ejection fraction it elevated blood peroxidase, plasma vitamin A and E concentrations. For patients with postinfarction cardiosclerosis there were, respectively, higher levels of blood peroxidase, plasmic vitamin A, red cell vitamin E, plasmic SH-groups and blood peroxidase, plasmic vitamins A and E.

Topics: Adult; Angina Pectoris; Angioplasty, Balloon, Laser-Assisted; Ascorbic Acid; Catalase; Ceruloplasmin; Female; Helium; Humans; Isotopes; Male; Middle Aged; Myocardial Infarction; Myocardium; Neon; Physical Exertion; Sclerosis; Vitamin A; Vitamin E

The inhibitory effect of a phosphate diester of alpha-tocopherol and ascorbic acid (EPC-K1) was examined in myocardial infarction induced in rats, in comparison with a selective 5-lipoxygenase inhibitor, AA-861. EPC-K1 significantly reduced the infarct size at 24 and 48 h after ligation, whereas AA-861 reduced it only at 48 h after ligation. In in-vitro experiments, EPC-K1 inhibited not only superoxide anion generation (IC50 = 4.2 x 10(-5) M), but also acid phosphatase activity (IC50 = 2.4 x 10(-5) M) in rat polymorphonuclear leukocytes in a concentration-dependent manner, while AA-861 showed marginal effects on both actions. These results indicated that EPC-K1 induced cardioprotective effects by affecting neutrophil functions by inhibition of generation of superoxide-anion generation and acid-phosphatase activity. The mechanism of the reduction of the infarct size by EPC-K1 differed from that of AA-861, which latter inhibited 5-lipoxygenase and the formation of leukotriene B4.

Topics: Animals; Antioxidants; Ascorbic Acid; Benzoquinones; Free Radical Scavengers; Lipoxygenase Inhibitors; Lysosomes; Male; Myocardial Infarction; Peroxidase; Rats; Rats, Sprague-Dawley; Superoxides; Vitamin E

There is controversy concerning the ability of antioxidant vitamins to reduce myocardial infarct size. We sought to determine whether a brief prophylactic treatment of vitamin C or vitamin C plus Trolox (a water-soluble form of vitamin E) could reduce myocardial infarct size in an experimental model. We used an anesthetized open-chest rabbit model in which a branch of the circumflex coronary artery was ligated for 30 minutes followed by 4 hours of reperfusion. Experiments were performed in a randomized and blinded fashion. An IV injection of normal saline pH balanced to 7.4 (control group n = 15), vitamin C (150 mg/kg, n = 14), or vitamin C plus Trolox (150 mg/kg plus 100 mg/kg, respectively, n = 15) was administered prior to coronary occlusion. Collateral blood flow during coronary occlusion was measured by radioactive microspheres, myocardial risk zone (AR) was assessed by blue dye injection, and myocardial infarct size (AN) was assessed by triphenyltetrazolium chloride staining. All rabbits received comparable ischemic insult: Collateral blood flow and AR were similar among all three groups. Infarct size, measured as a percent of AR, did not differ significantly among the controls (21%), vitamin C (29%), or the vitamin C plus Trolox (18%) groups. Therefore, in this ischemia/reperfusion model, antioxidant vitamins did not alter myocardial infarct size.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Chromans; Disease Models, Animal; Drug Therapy, Combination; Free Radical Scavengers; Heart Rate; Hydrogen-Ion Concentration; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Rabbits; Random Allocation; Staining and Labeling; Tetrazolium Salts; Vitamin E

The aim was to examine whether intracellular antioxidants play a role in myocardial preservation following hypoxic preconditioning.. Isolated working rat hearts were subjected to 30 min ischaemia and 30 min reperfusion. Control hearts were compared to hearts preconditioned with 10 min hypoxia. Left ventricular function and lactate dehydrogenase (LDH) release were measured in each group. Ascorbate dependent (ADAR) and thiol dependent (TDAR) components of the endogenous myocardial antioxidant reserve were assessed using electron spin resonance spectroscopy.. a Hypoxic preconditioning had no effect on left ventricular function after 10 min reoxygenation. During reperfusion, the hypoxically preconditioned hearts had a significantly increased survival rate, aortic flow, developed pressure, and dP/dtmax, and a reduced lactate dehydrogenase release, compared to non-preconditioned controls (P < 0.05). Preconditioned hearts also had significantly higher preservation of baseline ADAR (79%) and TDAR (96%) compared with control hearts, (70%) and (77%), respectively (P < 0.05).. Hypoxic preconditioning enhances functional recovery and reduces cell necrosis following global ischaemia in the working rat heart. This phenomenon may, in part, be mediated through enhanced ascorbate and thiol components of the antioxidant reserve.

Topics: Animals; Antioxidants; Ascorbic Acid; Electron Spin Resonance Spectroscopy; Heart; L-Lactate Dehydrogenase; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Perfusion; Rats; Rats, Sprague-Dawley; Sulfhydryl Compounds; Time Factors

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

Vitamin E supplements may decrease the incidence of myocardial infarction by inhibiting LDL oxidation to atherogenic moieties. We previously reported that hemin is a potent and relevant lipophilic source of iron that can rapidly intercalate into LDL, catalyzing its oxidation and promoting its cytolysis of endothelium. The effects of oral vitamin E on heme-catalyzed LDL oxidation and resulting endothelial damage were studied in 10 volunteers who received daily 800 I.U. of vitamin E with or without vitamin C (1000 mg) for 2 weeks. Prior, during, and 2 weeks after supplementation, plasma LDL was isolated and its number of alpha-tocopherol molecules, resistance to heme-catalyzed oxidation, and ability to damage porcine aortic endothelial cells were assayed. Vitamin E supplementation doubled the lag phase of LDL peroxidation as compared to control (104 +/- 18 vs. 58 +/- 11 min; p < 0.001) accompanied by an increase in alpha-tocopherol content of LDL particles (26 +/- 6 vs. 11 +/- 2 mol/mol; p < 0.001). Most intriguingly, LDL-mediated endothelial cell cytotoxicity was prevented (3 +/- 2% vs. 42 +/- 12%; p < 0.001). After a 2-week washout period, LDL alpha-tocopherol content, the lag time of LDL oxidation, and oxidized LDL-mediated cytolysis all returned to baseline levels. To determine whether supplements of vitamin E and vitamin C beneficially synergize in these effects, we monitored several volunteers on daily vitamin E alone or vitamin C alone. Vitamin E alone (at doses as low as 400 I.U./day) affected all measurements in a manner identical to that when it was taken with vitamin C. Vitamin C alone had no significant effect on these measurements. We conclude: dietary vitamin E supplementation provides cytoprotection against LDL oxidation-mediated endothelial cell injury, but this salutary effect is rapidly lost after supplementation is stopped.

Topics: Administration, Oral; Adult; Animals; Ascorbic Acid; Cells, Cultured; Drug Interactions; Endothelium, Vascular; Female; Heme; Humans; Hydrogen Peroxide; Lipoproteins, LDL; Male; Middle Aged; Myocardial Infarction; Oxidation-Reduction; Swine; Vitamin E

We have investigated the timescale of increased lipid peroxidation following successful early thrombolytic therapy for acute myocardial infarction and report for the first time reciprocal changes in plasma chain-breaking antioxidants. Sixty-seven patients were recruited following a first acute myocardial infarction within 6 h of the onset of symptoms and received 70 or 100 mg of recombinant tissue plasminogen activator (Actilyse) as two intravenous bolus injections 30 min apart. Serial blood samples were taken before administration of thrombolytic therapy and after 30 min, 60 min, 90 min, 6 h and 24 h. Coronary artery patency was assessed at 90 min by coronary angiography. Malondialdehyde (MDA), a marker of lipid peroxidation, and the chain-breaking antioxidants alpha-tocopherol, retinol and ascorbate were measured by high performance liquid chromatography. When the coronary artery was patent there was an early rise in plasma MDA (time 0 0.91 +/- 0.05 mumol.l-1) with levels peaking at 90 min (1.02 +/- 0.06, P < 0.05) and returning to baseline by 6 h (0.85 +/- 0.06), accompanied by reciprocal decreases in alpha-tocopherol (time 0 7.13 +/- 0.34 mumol.mmol-1 cholesterol, 90 min 6.64 +/- 0.33, P < 0.05) and retinol (time 0 1.99 +/- 0.10 mumol.l-1, 90 min 1.81 +/- 0.08, P < 0.05). Ascorbate levels did not change significantly until 24 h (time 0 29.5 +/- 4.9 mumol.l-1, 24 h 22.6 +/- 4.4, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Chromatography, High Pressure Liquid; Coronary Circulation; Female; Free Radicals; Humans; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Myocardial Infarction; Myocardial Reperfusion Injury; Recombinant Proteins; Thrombolytic Therapy; Tissue Plasminogen Activator; Vascular Patency; Vitamin E

Both Trolox (a water-soluble analogue of alpha-tocopherol) and ascorbic acid were more effective than superoxide dismutase or catalase in protecting myocyte cell cultures from free radical attack (induced by hypoxanthine and xanthine oxidase). In a canine model of two hours of left anterior descending coronary artery occlusion followed by four hours of reperfusion, Trolox and ascorbic acid reduced the area of infarction within the area at risk. The Trolox group received 500 mL of deoxygenated saline solution containing 2.0 g of Trolox, 3.0 g of ascorbic acid, and 18 mg of EDTA (ethylenediaminetetraacetic acid) infused into the ascending aorta 30 seconds before and four minutes after reperfusion. Saline controls received 500 mL of deoxygenated saline solution containing 18 mg of EDTA. The angioplasty group had unmodified reperfusion by simple release of the occlusion. The area at risk and the area infarcted were estimated with Evans blue and triphenyl tetrazolium hydrochloride stains, respectively. The ratio of the area infarcted to the area at risk was significantly lower with Trolox (angioplasty, 30.4% +/- 5.1%; saline, 20.8% +/- 2.9%; and Trolox, 8.7% +/- 4.0%; p less than 0.01). In summary, the antioxidants Trolox and ascorbic acid effectively reduced myocardial necrosis after ischemia.

Topics: Animals; Antioxidants; Ascorbic Acid; Benzopyrans; Cells, Cultured; Chromans; Disease Models, Animal; Dogs; Free Radicals; Heart; Hemodynamics; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Necrosis

The addition of ascorbate to ischemic rat hearts prevents the myocardial damage associated with reoxygenation. H2O2 oxidizes myoglobin (Mb+2) to higher oxidation states (Mb+4 and Mb+5) which are rapidly reduced by ascorbate. It is proposed that the operation of a myoglobin redox cycle, in which H2O2 causes the two-electron oxidation of myoglobin, is a critical determinant of reperfusion injury. Conversely, the reduction of myoglobin, in one-electron steps, may represent an essential protective mechanism against such injury in the heart.

Topics: Animals; Ascorbic Acid; Creatine Kinase; Hydrogen Peroxide; L-Lactate Dehydrogenase; Myocardial Infarction; Myocardial Reperfusion Injury; Myoglobin; Oxidation-Reduction; Rats; Rats, Inbred Strains; Spectrophotometry

The effects of CV-3611, a new free radical scavenger, on coronary circulation failure and infarct size after ischemia/reperfusion were studied in conscious beagle dogs. The dogs underwent occlusion of the left circumflex coronary artery for 60 min and then were reperfused for 14 days. The dogs were divided into three groups: a control group, a pre-treated group that received CV-3611 or alpha-tocopherol, and a post-treated group that received CV-3611. During occlusion, varying degrees of ventricular arrhythmia were noted; after reperfusion, the arrhythmia tended to become severe. CV-3611 at a daily dose of 10 mg/kg or 30 mg/kg and alpha-tocopherol at a daily dose of 60 mg/kg reduced the incidence of overall post-occlusion arrhythmia. Coronary blood flow in the control group was reduced to 20% of the preocclusion level at 7 days after reperfusion, whereas in the CV-3611 and alpha-tocopherol treated groups, the decreased coronary flow was remarkably suppressed. The infarct size for the CV-3611- and alpha-tocopherol-treated groups, measured at 14 days after reperfusion, was reduced by 70% when compared with the control group. Based on these observations, it is proposed that CV-3611 exerts its beneficial effects on ischemic tissue by protecting against oxygen free radical-mediated damage induced by ischemia/reperfusion.

Topics: Animals; Ascorbic Acid; Blood Pressure; Coronary Circulation; Coronary Disease; Dogs; Free Radicals; Heart Rate; Hemodynamics; Myocardial Infarction; Myocardial Reperfusion Injury; Vitamin E

The effect of two different combined treatments with vitamin E acetate and vitamin C on infarct size and recovery of regional myocardial function was investigated in ischemic, reperfused porcine hearts. The left anterior descending coronary artery was distally ligated in 30 thoracotomized pigs for 45 minutes followed by 3 days of reperfusion. Infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic (dye technique) myocardium. Regional myocardial function was assessed by sonomicrometry. Ten pigs received vitamin E acetate (12 gm intravenously three times for 1 week) before ischemic and vitamin C (4.4 gm intravenously) before reperfusion (therapy A). Another 10 pigs were treated with vitamin E acetate (12 gm intraarterially) and vitamin C (4.4 gm intravenously) during ischemia (therapy B). An additional 10 pigs served as a control group. Global hemodynamics did not differ significantly among the groups before and during ischemia. Mean plasma concentrations of vitamin E amounted to 107 micrograms/ml in group A, 16 micrograms/ml in group B, and 0.9 micrograms/ml in the control group at the onset of reperfusion. Therapy A reduced the size of the infarct from 73 +/- 12% to 47 +/- 16% of the region at risk (p less than 0.005) and improved regional systolic shortening from 0 +/- 7% to 11 +/- 6% at 3 days after reperfusion (p less than 0.01). Therapy B decreased the size of the infarct to 64 +/- 9% of the region at risk (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Ascorbic Acid; Drug Therapy, Combination; Free Radicals; Hemodynamics; Myocardial Infarction; Myocardial Reperfusion; Myocardium; Swine; Vitamin E

Vitamin A, E, C and B6 status was studied in 30 patients with myocardial infarction and in 19 age- and sex-matched patients after elective surgery or trauma. Plasma levels of the four vitamins studied were low, remained low or decreased transiently in both groups of patients during the acute catabolic response phase, and began to return to normal after the third day from the start of the catabolic response. These changes in plasma levels are therefore neither of any special pathophysiological importance in nor specific to myocardial infarction.

Topics: Adult; Aged; Ascorbic Acid; C-Reactive Protein; Humans; Middle Aged; Myocardial Infarction; Pyridoxine; Time Factors; Vitamin A; Vitamin E

Dietary intake as initially estimated by means of a 24-h recall has been related to the incidence of ischemic heart disease, stroke, and overall mortality during a 12-yr follow-up period in a prospective study of 1462 women representative of the general population. Energy intake was inversely correlated to the 12-yr incidence of myocardial infarction. The correlation was independent of age, indices of obesity, smoking habits, serum cholesterol, serum triglycerides, diabetes, systolic blood pressure, and physical activity. No correlation was found between dietary intake and incidence of stroke or overall mortality, nor was any correlation found between end-points and intake of fish, energy percentage of fat, protein, and carbohydrates. These observations suggest that suboptimal intake of nutrients may be an important factor in the pathogenesis of ischemic heart disease.

Topics: Adult; Animals; Ascorbic Acid; Cardiovascular Diseases; Cerebrovascular Disorders; Diet; Energy Intake; Female; Fishes; Humans; Middle Aged; Myocardial Infarction; Prospective Studies; Risk; Sweden

Indian and black patients admitted to King Edward VIII and R. K. Khan Hospitals with a diagnosis of cardiac infarction and diabetes mellitus were studied. The mean serum cholesterol levels were higher in the indian group. This preliminary study suggests a negative correlation between leucocyte ascorbic acid and serum cholesterol levels in Indians, especially in patients with infarction. This, however, does not preclude an effect of latent ascorbic acid deficiency on the vessel wall. The possible relevance of the findings to the development of atherosclerosis is discussed.

Topics: Adult; Age Factors; Ascorbic Acid; Black or African American; Black People; Cholesterol; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Humans; India; Leukocytes; Middle Aged; Myocardial Infarction; South Africa

Topics: Animals; Aprotinin; Ascorbic Acid; Drug Therapy, Combination; Glutamates; Glutamic Acid; Heart Failure; Ibuprofen; Myocardial Infarction; Myocardium; Nandrolone; Nandrolone Decanoate; Nifedipine; Potassium Magnesium Aspartate; Propranolol; Rabbits; Sodium Oxybate; Vitamin E

Topics: Animals; Ascorbic Acid; Flavin-Adenine Dinucleotide; Isoproterenol; Male; Myocardial Infarction; NAD; Rats; Rats, Inbred Strains; Vitamin A

Topics: Adult; Aged; Ascorbic Acid; Drug Therapy, Combination; Female; Glutathione; Humans; Male; Middle Aged; Myocardial Infarction; Oxidation-Reduction; Oxygen; Thiamine

Topics: Analgesia; Ascorbic Acid; Female; Heart; Humans; Magnesium; Male; Myocardial Infarction

Topics: Acute Disease; Ascorbic Acid; Humans; Leukocytes; Myocardial Infarction; Postoperative Period

After an acute myocardial infarction, there is an apparent acute fall in leucocyte ascorbic acid associated with an acute rise in white blood cells and serum cortisol. The apparent fall in leucocyte ascorbic acid is the result of the granulocytosis which occurs after the infarction. Estimations of ascorbic acid disclose that the granulocyte contains approximately half the ascorbic acid of the lymphocyte. When the granulocytosis subsides, the new population of white blood cells is depleted of ascorbic acid for at least 56 days, reflecting tissue desaturation which can be corrected by ascorbic acid supplements. Tissue desaturation is also reflected in subnormal serum ascorbic acid levels which persist also unless ascorbic acid supplements are given. Observations on normal subjects given infusions of tetracosactrin (Synacthen) show that adrenal stimulation can produce a similar rise in white blood cells and an apparent fall in leucocyte ascorbic acid concentration with the exception that the serum ascorbic acid remains unaltered. Therefore, while adrenal stimulation can mimic 'stress' with regard to the changes in the white blood cells, tissue depletion of ascorbic acid as reflected in the white blood cells and serum after a myocardial infarction requires a focus of damaged tissue.

Topics: Adrenal Glands; Aged; Ascorbic Acid; Cosyntropin; Female; Humans; Hydrocortisone; Leukocyte Count; Leukocytes; Male; Middle Aged; Myocardial Infarction

Fasting serum samples from 53 patients with an acute myocardial infarction were investigated for their vitamin C content during the first week of their illness. The vitamin C levels found were generally within the accepted normal limits. However, there were highly significant lower levels on the second to the fifth post-infarction days, as compared with those found on days six to eight.

Topics: Acute Disease; Ascorbic Acid; Fasting; Humans; Myocardial Infarction; Time Factors

Although the effect of cold and heat stress on myocardial metabolisms has been widely studied, this parameter has not been investigated over a wide range of environmental temperatures after myocardial infarction. Since high as well as low temperatures are known to adversely affect the myocardium, changes in enviromental temperature are likely to be of great importance to patients suffering from acute coronary insult. Therefore, the myocardial metabolism was studied at different environmental temperatures in albino rats with isoproterenol-induced infarct-like myocardial necrosis. Male albino rats weighing 100 to 150 g were selected for the study. The investigations included ECG (lead II), histology, serum free fatty acids (FFA), serum triglycerides (TGS), cardiac noradrenaline, cardiac glycogen, and adrenal ascorbic acid, after the induction of myocardial necrosis. The biochemical changes were minimum between 10 and 15 degrees C while, at 4 degrees C, marked changes were observed. No significant change was seen in the serum triglycerides.

Topics: Adrenal Glands; Alanine Transaminase; Animals; Ascorbic Acid; Aspartate Aminotransferases; Cardiomyopathies; Fatty Acids, Nonesterified; Glycogen; Heart; Isoproterenol; Male; Myocardial Infarction; Myocardium; Necrosis; Norepinephrine; Organ Size; Rats; Temperature

Topics: Adult; Aged; Ascorbic Acid; Ceruloplasmin; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardium; Oxidation-Reduction

Topics: Acupuncture Therapy; Adrenal Cortex Hormones; Adrenal Glands; Adrenocorticotropic Hormone; Animals; Ascorbic Acid; Blood Pressure; China; Environmental Exposure; Eosinophils; Guinea Pigs; Humans; Leukocyte Count; Medicine, East Asian Traditional; Myocardial Infarction; Panax; Phytotherapy; Plant Extracts; Plants, Medicinal; Rabbits; Rats; Stress, Physiological; Temperature; Vitamin E; Vitamins

Topics: Adrenal Glands; Aged; Ascorbic Acid; Aspartate Aminotransferases; Autopsy; Coronary Disease; Female; Humans; Hydrocortisone; Leukocyte Count; Leukocytes; Male; Middle Aged; Myocardial Infarction; Myocardium; Stress, Physiological; Time Factors

Topics: Ascorbic Acid; Humans; Myocardial Infarction; Time Factors; Warfarin

Topics: Acute Disease; Ascorbic Acid; Blood Transfusion; Diet; Diet Therapy; Duodenal Ulcer; Endoscopy; Esophageal and Gastric Varices; Gastritis; Gastrointestinal Hemorrhage; Hematemesis; Hernia, Diaphragmatic; Humans; Melena; Myocardial Infarction; Peptic Ulcer Hemorrhage; Radiography; Stomach Neoplasms; Vagotomy; Vitamin K

Topics: Age Factors; Ascorbic Acid; Cholesterol; Cooking; Humans; Lipoproteins; Myocardial Infarction

Topics: Arteriosclerosis; Ascorbic Acid; Calcium; Calcium, Dietary; Drug Therapy; Folic Acid; Geriatrics; Humans; Iron; Magnesium; Myocardial Infarction; Preventive Medicine; Procaine; Vitamin B Complex

Topics: Anticoagulants; Ascorbic Acid; Breast Feeding; Calcium; Calcium, Dietary; Common Cold; Dental Caries; Female; Fluorides; Humans; Infections; Iodine; Lactation; Myocardial Infarction; Penicillins; Pregnancy; Preventive Medicine; Silver Nitrate; Sulfonamides; Urinary Calculi

Topics: Ascorbic Acid; Coronary Artery Disease; Glutathione; Humans; Myocardial Infarction; Myocardial Ischemia; Myocardial Revascularization

Topics: Ascorbic Acid; Coronary Artery Disease; Glutathione; Humans; Myocardial Infarction; Myocardial Ischemia; Myocardial Revascularization

Topics: Adenosine Triphosphate; Ascorbic Acid; Bile Acids and Salts; Coumarins; Diet; Folic Acid; Heparin; Humans; Hypnotics and Sedatives; Khellin; Magnesium Sulfate; Myocardial Infarction; Purines; Quinidine; Salts; Sympathomimetics; Vitamin B Complex; Vitamin E; Vitamins