Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Circulating platelet aggregates formed in vivo were serially measured, and platelet-aggregation thresholds were determined in vitro in 82 patients with acute cerebral ischaemia. The percentage of aggregated platelets was increased in 53 patients with completed stroke (30.9% +/- 2.0) and in 29 patients with transient ischaemic attacks (34.1% +/- 2.3), all studied within 10 days of the acute event. These values were higher (P less than 0.001) than levels of aggregated platelets in 30 patients with non-vascular neurological disease (16.8% +/- 2.3). The percentage of aggregated platelets returned to normal 10 days to 6 wk after acute cerebral ischaemia. Aspirin and dipyridamole did not affect either the increase in or subsequent normalisation of circulating-platelet-aggregate levels in these patients. Platelet-aggregation sensitivity to adenosine diphosphate and adrenaline was also increased in patients with acute cerebral ischaemia, but this abnormally resolved during convalescence. Platelet activation is abnormal in acute cerebral ischaemia but usually returns to normal with or without anti-platelet therapy. This activation of platelets may contribute to the clinical manifestations of occlusive vascular disease.
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PMID:Platelet activation in acute cerebral ischaemia. Serial measurements of platelet function in cerebrovascular disease. 6 34

A review is given on the clinical studies performed with aspirin in patients with chronic vascular occlusions of the limbs and on studies in cerebral ischemia using aspirin and sulfinpyrazone. Aspirin reduces the risk of reocclusions in patients after vascular surgery and also reduces the risk of peripheral vascular occlusions in diabetic patients. In doses of 1.2-1.5 g/day it also reduces the frequency of transient ischemic attacks. Conclusive results of similar studies with sulfinpyrazone and dipyridamole can be expected of the ongoing studies. Aspirin has no effect on the course of glomerulonephritis in children. Warfarin plus dipyridamole seem to have some effect in patients renal allografts. Sulfinpyrazone and ASA reduced the incidence of shunt thromboses in hemodialyzed patients. Several case reports in patients with thrombocytemia or Raynaud's syndrome made it likely that treatment with antiplatelet drug reduces the incidence of vascular occlusions.
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PMID:Use of platelet inhibitor drugs in peripheral and cerebral vascular disorders. 36 58

Acute myocardial infarction is most commonly initiated by fissuring of an atheromatous plaque. Through such fissures the blood is exposed to thrombogenic constituents of the intima, causing thrombotic obstruction of the coronary artery. Why plaque fissuring occurs is not known. Our investigation is to establish which types of plaque undergo fissuring by relating their mechanical with their cellular and biochemical properties; and to quantify the distribution of fissures. Results so far indicate that fissures occur predominantly in plaques with lipid pools in one segment of intima, and that the commonest single site of fissuring is that of maximal stress concentration as predicted by computer modelling. The results also suggest that arterial spasm at the immediate site of fissuring is not involved, as more than half the fissures occur at sites where there is no residual medial smooth muscle. Obstructive coronary thrombosis is initiated in most cases by plaque fissure with local haemorrhage which induces intravascular platelet aggregation. Recent observations with novel techniques have provided evidence that platelet aggregation in vivo is initiated by ADP and potentiated by thromboxane A2 and thrombin, with actual contribution of exposed collagen still undetermined. These observations provide an explanation for the limited effectiveness of any simple platelet-inhibiting drug, including Aspirin, by itself whenever arterial, eg. coronary or cerebral thrombosis is initiated by haemorrhages into atheromatous plaques. On the other hand, Aspirin is significantly effective when myocardial infarction follows unstable angina and when strokes follow transient episodes of cerebral ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coronary thrombosis: pathogenesis and prevention. 210 21

Aspirin has been tested for its benefit in preventing cardiovascular disease in randomized trials in three categories of patients. In secondary prevention among those with a history of myocardial infarction (MI), stroke or transient cerebral ischemia, or unstable angina pectoris, 25 randomized trials demonstrated significant reductions from aspirin of 25% for the occurrence of an "important vascular event" (nonfatal MI, nonfatal stroke, or vascular death), 32% for nonfatal MI, 27% for nonfatal stroke, and 15% for vascular mortality. Among those evolving an MI, the Second International Study of Infarct Survival (ISIS-2) showed a significant reduction of 23% in five-week vascular mortality among those started on a one-month regimen of daily aspirin within 24 hours of the onset of symptoms of suspected MI. Aspirin also significantly reduced reinfarction, nonfatal stroke, and important vascular events. Finally, in primary prevention, the US Physicians' Health Study (PHS) showed a significant 44% reduction in the occurrence of a first MI among apparently healthy male physicians; numbers of strokes and vascular deaths were insufficient to permit conclusions for these endpoints. Thus, aspirin is of clear benefit in reducing MI, stroke, and vascular death in secondary prevention and among those evolving an MI. It is also beneficial in the primary prevention of MI among men over 40, but data concerning its effects on stroke and vascular death remain inconclusive.
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PMID:Prevention of cardiovascular disease: risks and benefits of aspirin. 223 Oct 66

The effect of short and long-term therapy with aspirin (50 mg/day) on platelet alpha granule secretion was studied in 11 healthy controls and 57 patients suffering from transient cerebral ischemic attacks (TIA) with and without accompanying diabetes and hypertension. Plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF 4) were measured as indicators of platelet alpha granule secretion. beta-TG and PF 4 levels were increased following cerebral ischemia. Aspirin treatment failed to suppress plasma levels of both proteins when measured a month and then a year after initiation of treatment. Therefore, these proteins may be poor indicators of platelet inhibition by aspirin.
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PMID:Platelet alpha granule secretion in cerebral ischemia: effect of short and long term low dose aspirin treatment. 245 69

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

A total of 243 patients who had reversible ischemic attacks (RIA) were submitted to clinical trial to determine whether dipyridamole (400 mg/day) (D) or aspirin (100 mg/48 hours) + dipyridamole (300 mg/day) (ASA + D) would produce significant reduction in the subsequent occurrence of RIA and completed stroke. One hundred and fifteen were selected for Group ASA + D and 71 were treated with dipyridamole only. The treatment groups were similar in relation to age, sex, risk factors, duration and presumed vascular territory of RIA, incidence of alterations of arterial supra-aortic trunks, cerebral infarct (CT scan), and platelet function. Patients were followed for a mean time of 21 months. At the end of the study, 21.7% of the ASA + D group and 19.7% in the D group had suffered new episodes of RIA or completed stroke (p = 0.88). Frequency of stroke (reversible ischemic neurologic deficit or completed stroke) was 7.8% in the ASA + D patients and 9.8% in the D patients (p = 0.83). Subgroup analysis did not show significant differences either. It is concluded that ASA + D has no significantly greater beneficial effect than that observed with D alone in the secondary prevention of atherothrombotic cerebral ischemia. However, a statistical Type II error cannot be excluded by the reduced number of recurrences.
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PMID:Low-dose acetylsalicylic acid (ASA) plus dipyridamole versus dipyridamole alone in the prevention of stroke in patients with reversible ischemic attacks. 332 18

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

Evaluating the use of antithrombotic drugs in artery disease has been a long and difficult process, which is far from complete. The aims of treatment have ranged from the primary prevention of myocardial infarction or stroke, through the restoration of blood flow to ischaemic organs in order to salvage threatened tissue, to the prevention of recurrent vascular occlusion. Drugs studied in depth by clinical trial include the oral anticoagulants, antiplatelet drugs (especially aspirin), and thrombolytic agents. Their results are considered under the headings of coronary artery disease, cerebral ischaemia, and peripheral vascular disease. Aspirin, with or without dipyridamole, prevents progression of unstable angina to myocardial infarction or death, probably reduces long-term mortality after myocardial infarction, and prevents aortocoronary bypass graft occlusion. It decreases the risks of stroke or death in patients with transient cerebral ischaemia, diminishes cardiovascular morbidity after a thrombotic stroke, and may improve the outcome after some kinds of surgery for peripheral vascular disease. The benefits of oral anticoagulant treatment to prevent artery occlusion remain poorly defined. Oral anticoagulants prevent systemic embolism in many groups of high-risk patients, and probably reduce the risk of recurrence after embolism has occurred. Whether their long-term use to prevent reinfarction in patients with a previous myocardial infarct can be justified remains uncertain. They are of little or no proven value in patients with transient cerebral ischaemia or thrombotic stroke. On the other hand, there is increasing support for early thrombolytic treatment after myocardial infarction, especially since two multicentre trials have now shown reduced mortality in patients treated with intracoronary streptokinase within 4-6 hours of infarction and a further large multicentre study also demonstrated reduced mortality in patients treated with early intravenous streptokinase. In addition, the local infusion of streptokinase leads to recanalization in a high proportion of patients with a recent peripheral artery occlusion who are poor candidates for surgery.
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PMID:The use of antithrombotic drugs in artery disease. 352 34

Two randomized, double-blind clinical trials in cerebrovascular disease are described. The Controlled trial of Aspirin in Cerebral Ischemia compared aspirin (650 mg twice daily) with placebo in medically and surgically treated groups of patients who had experienced transient ischemic attacks. The Randomized Trial of Aspirin and Sulfinpyrazone in Threatened Stroke compared aspirin (325 mg four times daily), sulfinpyrazone (200 mg four times daily) and aspirin plus sulfinpyrazone with placebo in patients with transient cerebral ischemia.
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PMID:Summary of design features: clinical trials of platelet-active drugs in cerebrovascular disease. 700 55


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