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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aspirin inhibits platelet function by acetylating platelet cyclo-oxygenase. When aspirin is administered in doses as low as 40-160 mg per day, it inhibits platelet cyclo-oxygenase activity by more than 80%. The effect of aspirin on platelet function is maintained for the life-span of the platelet and there is evidence that aspirin also acetylates platelets before they are released in the circulation and while they are still within megakaryocytes. Aspirin also inhibits the synthesis of PGI2 by vascular wall cells but compared to the platelet, this vessel wall effect is relatively short-lived and requires slightly larger doses of aspirin. In vivo studies in rabbits indicate that very high doses of aspirin are thrombogenic. However, there is no evidence that aspirin is thrombogenic in man even when administered in high therapeutic doses. The optimal antithrombotic dose of aspirin has not yet been determined. Clinically, impressive results have been obtained with low doses of aspirin (ranging from 100 to 300 mg per day) in preventing aorta coronary bypass thrombosis, in patients undergoing hemodialysis, and in patients with unstable angina. Aspirin is also effective in preventing stroke and death in patients with cerebral ischemia when administered in doses of approximately 1 gram per day. There are trends suggesting that aspirin is effective when administered in doses between 300 mg per day and 1500 mg per day in patients who have survived myocardial infarction. The side-effects of aspirin are mainly gastrointestinal and are dose-related. Generalized bleeding is very uncommon and limited mainly to patients with other hemostatic abnormalities or due to the concomitant use of anticoagulant therapy.
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PMID:Effect of aspirin on hemostasis and thrombosis. 330 53

Ponies with electromagnetic blood flow transducers implanted around the main pulmonary and left main coronary arteries, were used to evaluate effects of chronic sublethal endotoxin on cardiac output (CO), stroke volume, and left coronary blood flow (LCBF). Plasma thromboxane (TX), as indicated by TXB2, prostacyclin as indicated by 6-keto-prostaglandin (PG) F1 alpha, and hematologic and blood chemical values also were evaluated. Over 24 hours, 2 groups of ponies were given progressively increasing IV and intraperitoneal doses of Escherichia coli lipopolysaccharide (LPS) at 0, 6, 12, and 18 hours. Group 1 was not treated and group 2 was treated with flunixin meglumine, before each LPS insult. Initial LPS inoculation in group 1 led to 10-fold increases in TXB2 and 6-keto-PGF1 alpha values by 30 and 90 minutes, respectively. These eicosanoid values returned to base line by 6 hours after each insult. Although repeated LPS injections stimulated recurring high plasma concentrations of 6-keto-PGF1 alpha, TXB2 production became less with each successive LPS insult. Cardiac output decreased to 55% to 60% of base-line values in association with increased 6-keto-PGF1 alpha values. Left coronary blood flow could not be evaluated accurately. Severe lactic acidosis developed in group 1. Group-2 ponies remained clinically normal, indicating protection of cardiovascular function and peripheral perfusion with flunixin meglumine. Seemingly, flunixin meglumine helped to maintain acceptable cardiovascular function and tissue perfusion during endotoxemia. Flunixin meglumine given to healthy ponies had no effect on cardiovascular function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Equine endotoxemia: cardiovascular, eicosanoid, hematologic, blood chemical, and plasma enzyme alterations. 330 60

The classification, epidemiology, pathophysiology, diagnosis, and treatment of ischemic cerebrovascular disease (ischemic stroke) are reviewed, and the major drugs used in the prevention of this disease are discussed. Ischemic stroke is a major problem in terms of morbidity and mortality because of the high prevalence of atherosclerosis in the United States population. The pathogenesis of cerebral ischemia is multifactorial, beginning with an atherosclerotic plaque on the arterial wall that may result in stenosis or ulceration with subsequent thrombosis or embolization. Platelets may adhere to the exposed arterial wall endothelium, stimulating further platelet aggregation and accumulation of leukocytes and fibrin. Consequences of cerebral ischemia include transient ischemic attacks and brain infarcts. Diagnosis is based mainly on patient history and ancillary radiologic studies. Treatment of ischemic cerebrovascular disease is primarily preventive, since the brain has limited capacity to recover neurologic function after an infarction. Transient ischemic attacks are treated with either antiplatelet agents, anticoagulants, or surgery. Treatment of stroke is also preventive, although anticoagulation is sometimes used to prevent stroke progression. Agents that may reverse neurologic impairment following an acute stroke, such as prostacyclin, calcium-channel blockers, and opiate antagonists, are being investigated. Antiplatelet therapy is indicated in subsets of patients with cerebral vascular insufficiency. Anticoagulation therapy, if needed, should be given for only three to four months.
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PMID:Current concepts in clinical therapeutics: ischemic cerebrovascular disease. 331 77

Aspirin is of proven value as an antithrombotic drug. In unstable angina it reduces the risk of death and myocardial infarction by half. After a myocardial infarction it reduces the risk of death by about 10% and of coronary incidence (coronary death or definite myocardial infarction) by about 25%. These effects appear to be additive with those of beta-blocking drugs. Aspirin also reduces the risk of occlusion of aortocoronary saphenous vein grafts by about half. In transient cerebral ischaemia, aspirin may reduce the risk of stroke and death by 50%. In most clinical trials to date the daily dose of aspirin ranges from 325 mg to 1400 mg. Interest in very low doses of aspirin (less than 60 mg daily) is considerable but has yet to be translated into proven clinical benefit. Dipyridamole has not been shown to be effective as an antithrombotic when used alone. Its antiplatelet action ex vivo may be enhanced by combination with aspirin but clinical trials have shown relatively little advantage of the combination over aspirin alone. Sulphinpyrazone has not become established as a first line antithrombotic drug. Epoprostenol is useful in extracorporeal circulations to prevent platelet consumption and possibly in severe inoperable peripheral vascular disease.
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PMID:Aspirin and other antiplatelet drugs in the prophylaxis of thrombosis. 333 89

The cardiopulmonary effects of a third-degree scald burn involving the anterolateral chest wall was compared with a burn of equal size (30% of total body surface) to the flanks in anesthetized sheep with lung lymph fistulas. The chest-burn group was characterized by immediate decreases in cardiac output (6.5 to 3.0 L/min), central venous pressure (5 mm Hg to 0 mm Hg), pulmonary wedge pressure (10 mm Hg to 6 mm Hg), and urine output 1.5 ml/kg/hr to less than 0.5 ml/kg/hr. The temperature of pulmonary artery blood increased from 38 to 42 degrees C and plasma prostacyclin increased from 20 to 200 pg/ml. These changes were significantly different from those seen in the body sheep with burns. Initial fluid requirements necessary to restore filling pressures were 50% greater in the sheep with chest burns than in the sheep with body burns. An early decrease in static lung compliance was also seen after chest burn that was not the result of increased lung edema. A progressive decrease in compliance, urine output, and stroke output was also seen in the later postburn period (6 to 7 hours), which was significantly improved by a chest wall escharotomy. Postmortem analysis in the chest-burn group revealed a significantly increased malondialdehyde content, a reflection of increased oxygen radical-induced lipid peroxidation relative to the body burn. Pretreatment of the chest burn with ibuprofen, 12.5 mg/kg, prevented the initial vasodilator and lung compliance changes so that early cardiopulmonary status was identical to that seen with a body burn alone. Ibuprofen also decreased the lung tissue malondialdehyde content. We conclude that a burn involving the chest wall results in cardiopulmonary abnormalities, not seen after a body burn of a comparable size, which appear to be due to hyperthermia and an increased release of prostacyclin and O2 radicals.
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PMID:Early pulmonary and hemodynamic effects of a chest wall burn (effect of ibuprofen). 338 75

Organotypic cultures of rat cerebella were exposed to anoxia for 30 min. Prostacyclin (0.5 micrograms/ml medium) or 0.05 M Tris buffer pH 7.5 were added to the cultures immediately before exposure to anoxia. Cultures for histological, histoenzymatic and electron microscopic examination were taken immediately, 30 min and one, three, 24 and 72 h following anoxia. Cultures pretreated with prostacyclin showed a marked decrease in lactate dehydrogenase activity. Electron microscopic examination revealed that severe swelling and degenerative changes of neurons and glia induced by anoxia were much less pronounced in cultures treated with PGI2. Prostacyclin pretreatment also resulted in the appearance of morphological features of activation in glial cells. The results indicate that prostacyclin exerts a cytoprotective effect on the nerve tissue in vitro, predominantly reducing cell swelling and acidosis. This direct protection, besides vascular action of prostacyclin, may provide a basis for its beneficial clinical effect in ischemic stroke.
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PMID:The effect of prostacyclin on the morphological and enzymatic properties of CNS cultures exposed to anoxia. 351 27

Nutritional antioxidants support prostacyclin synthesis by preventing lipid hydroperoxide-mediated inhibition of prostacyclin synthetase. Recent preliminary clinical studies indicate that supplementary antioxidants exert antithrombotic effects in vivo that are most likely attributable to enhanced prostacyclin production. Optimal antioxidant nutrition may thus have preventive and therapeutic value for disorders in which inappropriate platelet aggregation plays an etiologic role, including MI, stroke, atherogenesis, pre-eclampsia, and the vascular complications of diabetes. In light of evidence that platelet aggregation encourages the implantation of hematogenous tumor metastases, supplemental antioxidants should also impede tumor dissemination--an effect which will be complemented by the immunostimulant actions of these nutrients. By exerting anticarcinogenic, immunostimulant and anti-metastatic effects, nutritional antioxidants should act to inhibit neoplasia at each stage of its development.
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PMID:An antithrombotic role for nutritional antioxidants: implications for tumor metastasis and other pathologies. 352 Feb 53

This study characterizes the effect of dazmegrel, a thromboxane synthetase inhibitor, on platelet function in the dog and introduces its potential use in combination with aspirin therapy. Ex vivo testing of dazmegrel alone was performed with three dosages and three administration regimens. Platelet aggregation response, malondialdehyde formation and prostaglandin metabolites generation were evaluated. To maintain complete thromboxane A2 inhibition, dazmegrel had to be given 3 times per day at dosages of not less than 6 mg/kg. The same result was achieved with a single daily administration of combined dazmegrel and aspirin in equal dosages of 3 mg/kg. Dazmegrel, both alone and with aspirin, increased and sustained heightened levels of prostacyclin, unlike the simultaneous inhibition of both prostaglandin metabolites seen with aspirin therapy alone. Because the combination of dazmegrel and aspirin effectively blocks thromboxane A2 formation and also enhances prostacyclin formation, the synergistic action of these agents increases their combined antiplatelet effect to a level not attainable by either agent alone. The significance of this combined therapy warrants further experimental study and may soon merit clinical trial for the prevention of stroke and other major thrombotic complications.
Stroke
PMID:A new combination therapy for selective and prolonged antiplatelet effect: results in the dog. 352 Sep 78

To explain the high neonatal mortality from peritonitis-induced septic shock despite current resuscitation practices, the efficacy of dopamine, naloxone, and prostacyclin was evaluated in an experimental neonatal model. Hemodynamics were monitored and survival was measured in anesthetized neonatal swine, which were subjected to fatal fecal-Escherichia coli peritonitis-induced septic shock. All the animals received fluid resuscitation, antibiotics, and bicarbonate to correct acidosis. Pharmacologic resuscitation began when cardiac output dropped below baseline in the experimental groups. Although significant differences were observed between groups in cardiac output, mean arterial and mean pulmonary arterial pressures, left ventricular stroke work, stroke volume, and pulmonary vascular resistance indices (P less than 0.02), and each animal exhibited favorable hemodynamic responses during the first several hours of dopamine and naloxone infusion, these drugs failed to prolong survival. Also, 5 of the 9 naloxone-treated pigs (56%), died with histologically proven intestinal ischemia (P less than 0.02). Thus, dopamine, naloxone, and prostacyclin (at doses commonly recommended for the treatment of septic shock) fail to positively influence the fatal course of this condition, and the use of naloxone in this model is associated with profound intestinal ischemia.
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PMID:Comparative effects of dopamine, naloxone, and prostacyclin in the resuscitation of fecal-Escherichia coli peritonitis-induced septic shock in neonatal swine. 352 48

Three different levels of global forebrain ischemia were induced in rats and their plasma levels of Thromboxane B2 (TXB2) and 6 Keto PGF1 alpha were determined to investigate the relation between severity of ischemia and eicosanoid production. Ischemia stimulates the activity of cellular lipase whose actions cause deacylation of brain phospholipids and release of free fatty acids. Arachidonic acid (A.A.) is one of the predominant fatty acids which is liberated in brain after ischemia. A.A. is the primary substrate for the synthesis of prostaglandins (PGs), Thromboxane A2 (TXA2) and Prostacyclin (PGI2), which play an important role in regulation of platelet aggregation and vasotonus. Thromboxane is a potent platelet aggregator and vasoconstrictor. On the other hand, PGI2 has the opposite nature. Therefore it can be considered that PGs and moreover, the balance of TXA2 and PGI2 may have an intimate relation to the development of cerebral ischemia. Three different levels of ischemia were produced by bilateral carotid artery ligation (BLCL) using three kinds of rats with different blood pressure ranges, namely, SHRSP (Stroke-prone spontaneously hypertensive rats), SHRSR (Stroke-resistant spontaneously hypertensive rats) and WKY (Wistar kyoto rats). It is known that higher pressure groups suffer severe ischemia by BLCL procedure. Hypertensive rats (SHRSP, SHRSR) were originally produced from WKY. The experimental animals used were about 300 gr and 16 weeks old male rats. The plasma and brain TXB2 and 6 Keto-PGF1 alpha, stable metabolites of TXA2 and PGI2 were measured by radioimmunoassay. The chronological changes of brain and plasma PGs levels after ischemia using SHRSR were also investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of bilateral common carotid artery ligation on prostaglandin levels (TXA2, PGI2) in spontaneously hypertensive rats (SHRSP, SHRSR) and normotensive rats (WKY)]. 352 27


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