salicylates and Myocardial-Ischemia

The mean follow-up in the clinical trials of antiplatelet drugs in the secondary prevention of ischemic atherothrombotic stroke ranges from 1 to 5.5 years. Thus, the safety and efficacy of these drugs in the very long term is not totally documented. We have assessed the safety and effectiveness of triflusal and aspirin for a very long-term period in the secondary prevention of patients with ischemic atherothrombotic stroke.. Patients with atherothrombotic ischemic stroke, including TIA, who participated in randomized clinical trials of triflusal versus aspirin were included in the study. The period of recruitment was between 1983 and 1999. After finishing their participation in the clinical trials, patients were followed up in the Neurology Department of our hospital. All patients were treated with aspirin or triflusal during a mean period of 17.2 years. Groups were comparable with respect to sex, age, risk factor and etiology of the stroke. Adverse events and vascular events (including stroke recurrence, ischemic heart disease and vascular death) that appeared throughout the study were registered. Statistical analysis was performed using the statistical package SPSS 15.0 for Windows. Kaplan-Meier curves and the log-rank test were used to compare treatments.. A total of 441 patients (305 men) with a mean age (±SD) of 51.1±12.4 years were included in the study; 288 patients (65.3%) were treated with triflusal and 153 with aspirin. There were no statistically significant differences between aspirin and triflusal concerning new vascular events (72.5 vs. 60.4%; p=0.28), stroke recurrence (49.7 vs. 46.5%; p=0.53), ischemic heart events (54.9 vs. 55.6%; p=0.90), vascular death (25.5 vs. 24%; p=0.73) and global mortality (42.5 vs. 42%; p=0.92). The incidence of serious bleeding (upper digestive tract hemorrhage and cerebral hemorrhage) was 18.3% in aspirin-treated patients and 5.5% in triflusal-treated patients (p<0.001). In reference to other adverse events, no significant differences were found between aspirin and triflusal.. In the secondary prevention of ischemic stroke, very long-term treatment with triflusal or aspirin seems to have a similar efficacy, but triflusal is safer with a lower hemorrhagic risk. Triflusal may be an alternative therapy, particularly in patients who present aspirin resistance.

Topics: Aged; Aspirin; Brain Ischemia; Dyspepsia; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Intracranial Arteriosclerosis; Ischemic Attack, Transient; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Platelet Aggregation Inhibitors; Recurrence; Salicylates; Secondary Prevention; Vascular Diseases

The aim of the study was to investigate the effects of the antiplatelet agent triflusal on the changes in platelet function in patients who underwent a cardiopulmonary bypass for coronary arteries (CABG). In 20 surgical patients, blood was sampled before and at the conclusion of surgery, 48 h later (in the intensive care unit), and after 10 days of treatment with 600 mg/day triflusal (triflusal was administered from the first day after surgery). Adenosine diphosphate (ADP) and collagen-induced platelet aggregation in whole blood, granular release of beta-thromboglobulin and platelet release of thromboxane B2 were measured. Basal values were compared with results in a group of ten healthy volunteers. All platelet determinations of activation were higher in coronary patients than in healthy volunteers. Immediately after CABG, the platelet reactivity to ADP and collagen were significantly lower, and release of beta-thromboglobulin and thromboxane B2 were higher, than in the pre-CABG samples. During the patient's stay in the intensive care unit, all values tend to return to pre-CABG values. Triflusal inhibits both platelet beta-thromboglobulin (63% with respect to the post-CABG value) and thromboxane B2 (91% with respect to the post-CABG value) release. Platelet aggregation after 10 days of triflusal treatment tended to return to the pre-CABG values. In conclusion, Triflusal reduces platelet activation caused by the coronary artery bypass graft surgery.

Topics: Adenosine Diphosphate; Adult; Aged; beta-Thromboglobulin; Collagen; Coronary Artery Bypass; Erythrocyte Count; Female; Hematocrit; Hemoglobins; Humans; Leukocyte Count; Male; Middle Aged; Myocardial Ischemia; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Salicylates; Thromboxane B2; Time Factors

Topics: Aged; Aspirin; Drug Hypersensitivity; Female; Fibrinolytic Agents; Graft Occlusion, Vascular; Humans; Male; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Salicylates; Stents

Reactive oxygen/nitrogen species suppress myocardial oxygen consumption. In this study, we determined that endogenous hydrogen peroxide through dismutation of superoxide enhances postischemic myocardial blood perfusion and oxygen consumption. Electron paramagnetic resonance oximetry was applied to monitor in vivo tissue Po2 in mouse heart subjected to regional ischemia reperfusion. Heart rate, arterial blood pressure, blood flow, infarction, and activities of mitochondrial NADH dehydrogenase and cytochrome c oxidase were measured in six groups of wild-type (WT) and endothelial nitricoxide synthase knock-out (eNOS(-/-)) mice treated with phosphate-buffered saline (PBS), superoxide dismutase mimetic (SOD(m)) M40403 [a manganese(II)-bis(cyclohexylpyridine)-substituted macrocyclic superoxide dismutase mimetic, C21H35Cl2MnN5], 10006329 EUK 134 [EUK134, manganese 3-methoxy N,N(1)-bis(salicyclidene)ethylenediamine chloride], and SOD(m) plus glibenclamide to study the protective effect of hydrogen peroxide via dismutation of superoxide on the activation of sarcolemmal potassium channels. In the PBS group, there was an overshoot of tissue Po2 after reperfusion. Treatment with SOD(m), EUK134, and SOD(m) + glibenclamide protected mitochondrial enzyme activities, reduced infarct size, and suppressed the postischemic hyperoxygenation. In particular, in the SOD(m)-treated group, there was a transient peak of tissue Po2 at 9 min after reperfusion, which was dependent on endogenous hydrogen peroxide but not nitric oxide formation as it appeared in both WT and eNOS(-/-) mice. Blood flow and rate pressure product were higher in the SOD(m) group than in other groups, which contributed to the transient oxygen peak. Thus, SOD mimetics protected mouse heart from superoxide-induced reperfusion injury. With treatment of different SOD mimetics, it is concluded that endogenous hydrogen peroxide via dismutation of superoxide at reperfusion enhances postischemic myocardial blood perfusion and mitochondrial oxygen consumption, possibly through activation of sarcolemmal ATP-sensitive potassium channels.

Topics: Animals; Coronary Circulation; Electron Spin Resonance Spectroscopy; Glyburide; Hemodynamics; Hydrogen Peroxide; KATP Channels; Male; Mice; Mice, Inbred C57BL; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Nitric Oxide; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Organometallic Compounds; Oximetry; Oxygen Consumption; Peroxynitrous Acid; Salicylates; Superoxide Dismutase

The present study examined whether opening of an ATP-sensitive K(+) (K(ATP)) channel can induce hydroxyl free radical ((*)OH) generation in the rat myocardium. Sodium salicylate in Ringer's solution (0.5 nmol/microl/min) was infused directly through a microdialysis probe to detect the generation of (*)OH as reflected by the nonenzymatic formation of 2,3-dihydroxybenzoic acid (DHBA). Induction of cromakalim (100 microM), a K(ATP) channel opener, through the microdialysis probe significantly increased the level of 2,3-DHBA. Another K(ATP) channel opener, nicorandil, also increased the level of 2,3-DHBA. When iron(II) was administered to cromakalim-pretreated animals, a marked elevation of DHBA was observed, compared with iron(II) only-treated animals. A positive linear correlation between iron(II) and formation of (*)OH, trapped as DHBA in the dialysate, was shown (r(2) = 0.988). When corresponding experiments were performed with nicorandil-treated animals, a positive linear correlation between iron(II) and DHBA in the dialysate was shown (r(2) = 0.988). However, the presence of glibenclamide (1-50 microM) decreased the cromakalim-induced 2,3-DHBA formation in a concentration-dependent manner (IC(50) = 9.1 microM). 5-Hydroxydecanoate (5-HD; 100 microM), another K(ATP) channel antagonist, also decreased cromakalim-induced (*)OH formation. The IC(50) value for 5-HD against cromakalim-evoked increase in 2,3-DHBA was 107.2 microM. In the presence of glibenclamide (10 microM), the heart was subjected to myocardial ischemia for 15 min by occlusion of the left anterior descending coronary artery (LAD). When the heart was reperfused, the normal elevation of 2,3-DHBA in the heart dialysate was not observed in animals pretreated with glibenclamide (10 microM). When corresponding experiments were performed with 5-HD (100 microM) pretreated animals, the same results were obtained. These results suggest that opening of cardiac K(ATP) channels may cause (*)OH generation.

Topics: Adenosine Triphosphate; Animals; Anti-Arrhythmia Agents; Antihypertensive Agents; Cromakalim; Decanoic Acids; Dose-Response Relationship, Drug; Ferrous Compounds; Glyburide; Hydroxy Acids; Hydroxybenzoates; Hydroxyl Radical; Hypoglycemic Agents; Inhibitory Concentration 50; Iron Chelating Agents; Male; Microdialysis; Myocardial Ischemia; Myocardium; Nicorandil; Potassium Channel Blockers; Rats; Rats, Wistar; Salicylates; Time Factors

To find out how many patients older than 64 years of age seen in a primary health care (PHC) centre receive antiplatelet drugs for secondary prevention of coronary heart disease (CHD), as well as by whom they are prescribed, which drug is chosen, and what are its contraindications, unwanted effects and motives for ending therapy.. Description of all cases of CHD among patients older than 64, identified through the audit of clinical records.. Urban health care centre with 23,702 inhabitants, with 2,742 over 64, 2,660 of whom have clinical records.. Patients over 64 with CHD, seen in the health centre within 1993.. Age, sex, type of CHD, therapy with a platelet aggregation inhibitor, drug used, dose, prescriptor, adverse events, contraindications.. We identified 179 cases of CHD, a prevalence of 6.7%, of which 60.9% were male. 94 patients received an antiplatelet drug: aspirin (88.3%), dypiridamol and triflusal (5.3% each) and ticlopidine (1 case). 111 patients were adequately treated, including 84 given aspirin or ticlopidine, 12 patients in which therapy was ended due to adverse events, and 15 patients in which use of antiaggregant drugs was contraindicated. All prescriptions originating from general practitioners were for aspirin, while specialists prescribed other drugs in 11% of cases.. Two-thirds of patients with CHD were correctly treated. Aspirin is the antiaggregant drug most frequently used, particularly among PHC physicians. Even low doses of aspirin were associated with interruptions of therapy due to adverse events.

Topics: Age Factors; Aged; Aged, 80 and over; Aspirin; Dipyridamole; Drug Prescriptions; Family Practice; Female; Humans; Male; Medical Audit; Medicine; Myocardial Ischemia; Platelet Aggregation Inhibitors; Prevalence; Primary Health Care; Salicylates; Spain; Specialization; Ticlopidine; Urban Population

We examined in vivo monitoring of hydroxyl radical (.OH) generation during myocardial ischemia for 30 min by occluding the left anterior descending (LAD) in dog heart using a microdialysis technique. The hydroxyl radical reacts with salicylate and generates 2,3- and 2,5-dihydroxybenzoic acids (DHBA) which can be measured electrochemically in picomole quantity by a high pressure liquid chromatography-electrochemical (HPLC-EC) procedure. When the premature ventricular contraction (PVC) occurred at almost 25 sec intervals, marked elevation of the levels of 2,3- and 2,5-DHBA was observed in the heart dialysate of 30-min ischemia. This study demonstrated the generation of .OH in the canine heart subjected to 30-min ischemic insult.

Topics: Animals; Chromatography, High Pressure Liquid; Dogs; Gentisates; Hydroxybenzoates; Hydroxyl Radical; Microchemistry; Microdialysis; Myocardial Contraction; Myocardial Ischemia; Salicylates; Salicylic Acid

Recent studies have suggested the ability of salicylic acid (SA) to trap the hydroxyl radicals (.OH) generated in reperfused ischaemic myocardium. This study was designed to examine the effect of SA on reperfusion-induced arrhythmias and postischaemic ventricular dysfunction. Isolated rat hearts perfused by the Langendorff technique were preperfused with SA for 10 min. Hearts were then made ischaemic for 30 min, followed by 30 min of reperfusion. The left-ventricular contractile functions, including left-ventricular developed pressure (LVDP) and its first derivative (LV dp/dt), and creatine kinase (CK) release, were determined before and after ischaemia. Epicardial electrocardiograms (ECG) were also employed to analyse the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF). SA improved LVDP and LV dp/dt, and reduced CK release, as compared to the control group (p < 0.05). The incidence of VT and VF during reperfusion was also significantly reduced by SA (p < 0.05). Analysis of tissue thiobarbituric acid-reactive products indicates that SA decreased oxidative stress during reperfusion. In conclusion, these results suggest that SA reduces ventricular dysfunction and attenuates ventricular arrhythmias by trapping OH radicals upon reperfusion in isolated rat hearts.

Topics: Animals; Anti-Arrhythmia Agents; Creatine Kinase; Electrocardiography; Free Radical Scavengers; Hydroxyl Radical; In Vitro Techniques; Male; Myocardial Ischemia; Rats; Rats, Sprague-Dawley; Salicylates; Salicylic Acid; Tachycardia, Ventricular; Thiobarbituric Acid Reactive Substances; Ventricular Fibrillation; Ventricular Function, Left; Ventricular Pressure

Direct evidence for substantial mobilization of copper in the coronary flow immediately following prolonged, but not short, cardiac ischemia is presented. In the first coronary flow fraction (CFF) of reperfusion (0.15 ml), after 35 min of ischemia, the level of copper (as well as of iron) was 8- to 9-fold higher than the preischemic value. The levels in subsequent CFFs decreased and reached the preischemic value, indicating that both metals appear in a burst at the resumption of coronary flow. When the first CFF was used in a reaction mixture containing ascorbate and salicylate, the latter underwent chemical hydroxylation and was converted to its dihydroxybenzoate derivatives. Likewise, this CFF promoted the ascorbate-driven DNA degradation. Subsequent 150 CFFs were serially collected and demonstrated low activities. Following 18 min of ischemia, the copper level in the first CFF of reperfusion was only 15% over the preischemic value. In contrast, the mobilization of iron into coronary flow was significant but markedly lower than after 35 min. The levels of copper and the redox activity of the first CFF correlated well with the degree of loss of cardiac function, after 18 and 35 min of ischemia, respectively. After 18 min of ischemia, cardiac function was about 50% and the damage is considered reversible, whereas after 35 min the functional loss exceeded 80% and is considered irreversible. These results are in accord with the causative role that copper and iron can play in heart injury following ischemia, by virtue of their capacity to catalyze the production of hydroxyl radicals, and could lead to the development of new modalities for intervention in tissue injury.

Topics: Animals; Copper; Coronary Circulation; DNA Damage; Hemodynamics; In Vitro Techniques; Iron; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Oxidation-Reduction; Predictive Value of Tests; Rats; Rats, Sprague-Dawley; Salicylates; Salicylic Acid; Time Factors