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

Ticlopidine inhibits platelet aggregation induced by adenosine diphosphate (ADP) and most other platelet agonists in ex vivo studies of human platelets. The drug also improves other abnormalities of platelet function seen in patients with cerebrovascular disease, peripheral arterial disease, ischaemic heart disease or other conditions involving platelet hyperaggregation. Abnormal platelet activity has been implicated in a variety of clinical conditions in which patients are at high risk of thromboembolic events, and thus the effectiveness of ticlopidine has been investigated in such patients. Since the initial review of the drug appeared in the Journal, data from several large multicentre studies have shown that ticlopidine has a substantial benefit to offer patients who have experienced transient ischaemic attacks or stroke, and in those with peripheral arterial disease or ischaemic heart disease. Ticlopidine reduces the incidence of further stroke, myocardial infarction or vascular death, and is superior to placebo and aspirin in this regard in studies of patients with recent stroke or transient ischaemic attacks, or intermittent claudication. Ticlopidine is equally effective in both men and women and also improves symptoms of claudication in patients with peripheral arterial disease, and appears to reduce anginal pain. Patients with subarachnoid haemorrhage and sickle cell disease have shown some improvement with ticlopidine administration. The drug reduces thromboembolic events and re-stenosis in patients undergoing haemodialysis and cardiac surgery, and appears to prevent the progression of nonproliferative diabetic retinopathy. Ticlopidine in large clinical trials is associated with a higher incidence of adverse effects than placebo and an overall incidence similar to aspirin. Most adverse effects do not require withdrawal of treatment. Gastrointestinal symptoms (particularly diarrhoea) are most common, occurring almost twice as frequently with ticlopidine as with aspirin. Other adverse effects associated with ticlopidine include skin rash, haemorrhagic disorders, and haematological effects; these latter effects require careful monitoring of patients during the initial weeks of therapy. In conclusion, ticlopidine is a valuable addition to the prophylactic treatments available for the management of patients with cerebrovascular disease, peripheral arterial disease or ischaemic heart disease, who present a high risk of thromboembolic events. Although tolerability may be a problem for some patients, the overall benefit conferred by the drug would appear to outweigh this potential disadvantage. Because of its antiplatelet activity, ticlopidine has a promising role in other disorders mediated by platelet dysfunction. However, the precise role of the drug in these additional therapeutic indications awaits clarification with wider clinical experience.
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PMID:Ticlopidine. An updated review of its pharmacology and therapeutic use in platelet-dependent disorders. 222 15

The trigger of the coagulopathy that complicates heat stroke is obscure, but direct platelet activation by heat is a possibility we set out to study. Platelet rich plasma (PRP), prepared from blood donors, was incubated at increasing temperatures (38-45 degrees C) and then platelet aggregation was undertaken in response to decreasing low doses of ADP (less than 2.0 mumol/l). Hyperaggregability was manifested when the incubation temperature reached 43 degrees C and was maximum at 44 degrees C before complete inhibition of responses at 45 degrees C. The platelet hyperactivity induced by heating at 44 degrees C persisted after reincubating PRP samples at 37 degrees C. These platelet responses could not be triggered in PRP samples prepared from subjects after the overnight ingestion of aspirin or after the addition of aspirin to PRP before starting the heating procedure. However, aspirin was less effective when added to PRP after the appearance of the heat-induced hyperaggregability. In conclusion, these results indicate that platelets can be activated directly by heat. This mechanism which may be operational in heat stroke, is unaffected by cooling (body cooling being basic in the management of heat stroke) but can be prevented by the early administration of aspirin.
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PMID:Direct activation of platelets by heat is the possible trigger of the coagulopathy of heat stroke. 231 Jul 1

We studied adenosine diphosphate-induced platelet aggregation and the associated release of thromboxane B2 in platelet-rich plasma from 88 patients with subarachnoid hemorrhage and 26 healthy controls. During the first 3 days after subarachnoid hemorrhage, the patients showed significantly decreased (p less than 0.05) platelet aggregability and thromboxane release relative to the controls, but these effects disappeared in a few days. Platelet count increased for 3 weeks after subarachnoid hemorrhage. Surgery in 67 patients was followed by significant increases in platelet aggregability (p less than 0.05) and thromboxane release (p less than 0.001). Greatest thromboxane release was found in the eight patients showing delayed (postoperative) ischemic deterioration with a permanent neurologic deficit. Although platelet hyperaggregability and increased thromboxane release were particularly prominent in these eight patients, the role of these hematologic parameters in the pathogenesis of delayed ischemic deterioration remains unclear.
Stroke 1990 Apr
PMID:Platelet thromboxane release after subarachnoid hemorrhage and surgery. 232 38

We studied platelet function in 41 patients with subarachnoid hemorrhage who were randomized to receive either nimodipine or placebo in a double-blind fashion. Nimodipine was given to 21 patients, intravenously for 7-10 days and then orally until 21 days after the subarachnoid hemorrhage. The other 20 patients received placebo in a similar manner. Nimodipine did not significantly influence platelet aggregability. For the first 1-5 days after the subarachnoid hemorrhage, nimodipine treatment did not have any notable effect on adenosine diphosphate-induced platelet thromboxane B2 release, but a significant (p less than 0.05) inhibitory effect was observed thereafter. During intravenous administration, nimodipine prevented the increase in thromboxane release otherwise observed after subarachnoid hemorrhage. Concomitant with the decrease in thromboxane release, nimodipine increased the platelet count both before and after surgery so that the capacity for thromboxane formation per liter of blood decreased less than expected on the basis of thromboxane release per 10(7) platelets. Our study suggests that nimodipine might diminish the chance of cerebral ischemia by inhibiting platelet thromboxane release.
Stroke 1990 Sep
PMID:Effect of nimodipine on platelet function in patients with subarachnoid hemorrhage. 239 64

The incidence of second wave of platelet aggregation induced by a small dose of ADP (1 mumol/l) was compared with plasma levels of beta-thromboglobulin in 81 normal individuals, 34 patients with acute myocardial infarction, 11 patients with acute cerebrovascular disease and 26 patients with renal disease. Platelet hyperaggregability was observed in 7% of normal individuals. Plasma levels of beta-thromboglobulin were higher in normal individuals over 60 years of age (48 vs. 32 micrograms/l). In contrast, hyperaggregability was observed in 79% of patients with acute myocardial infarction and in 64% of those with acute cerebrovascular disease. Median plasma levels of beta-thromboglobulin were also significantly elevated in patients with acute myocardial infarction (82 micrograms/ml) or acute cerebrovascular disease (99 micrograms/l). Levels of beta-thromboglobulin in plasma were significantly higher in those patients who demonstrated hyperaggregability. In patients with renal disease only 12% had signs of hyperaggregability. Nevertheless their plasma levels of beta-thromboglobulin were elevated (76 micrograms/l) and correlated with the serum creatinine values. These investigations indicate that patients with acute myocardial infarction or stroke have hyperreactive platelets and evidence of increased platelet inactivation in the circulation. However, evaluation of increased levels of beta-thromboglobulin requires consideration of renal function.
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PMID:Relationship between platelet aggregation and plasma beta-thromboglobulin levels in arterio-vascular and renal diseases. 240 89

In 14 patients with acute myocardial infarction, a 24-hour Iloprost infusion was started with a mean delay of 309 +/- 22 minutes from onset of symptoms. Patients were haemodynamically monitored with a pulmonary artery catheter and an arterial cannula. The dose of Iloprost was 1-4 ng kg-1 min-1 and titrated according to blood pressure and systemic vascular resistance. When 2.0-4.0 ng kg-1 min-1 of Iloprost were infused, 5 out of 10 patients required dose reduction due to hypotension, nausea or both. However, in all patients the infusion period was completed as planned. Acute reductions of systolic blood pressure and vascular resistance were seen, whereas stroke volume increased and heart rate remained unchanged. The infusion of Iloprost caused profound inhibition of ADP-induced platelet aggregation but no significant changes in plasma values for platelet-specific proteins or thromboxane B2 were recorded. It is concluded that it was possible to safely administer Iloprost over 24 hours in the early phase of acute myocardial infarction and profound anti-aggregatory effects were observed. These findings should be evaluated in a controlled study.
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PMID:Central haemodynamic and antiplatelet effects of iloprost--a new prostacyclin analogue--in acute myocardial infarction in man. 244 Jun 82

We examined platelet aggregability during nocturnal sleep and daytime wakefulness in patients with a history of sleep-related stroke onset (SOS) and compared it to that of matched awake-onset stroke (AOS) patients and controls without evidence of vascular disease. Aggregability was evaluated in-vitro at least seven weeks following stroke onset. Platelets were more aggregable to ADP, collagen and arachidonic acid (AA) during both sleep and wakefulness in patients with AOS (p less than 0.01). No significant difference in the mean aggregation thresholds during sleeping or waking periods were found between SOS and control groups. However, platelets were significantly more responsive to AA during sleep than during wakefulness in the SOS patients (p less than 0.01). This difference was confined to the subgroup of SOS patients who had experienced nocturnal as opposed to daytime sleep-related stroke onset, suggesting that the observed difference in platelet responsiveness to AA may be related to a circadian fluctuation in platelet aggregability rather than to a sleep-related fluctuation. Significant sleep-related changes in platelet aggregability were not identified in the other two groups.
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PMID:Platelet aggregability in sleep-related stroke. 249 75

We compared combination therapy with low-dose aspirin plus ticlopidine to therapy with aspirin alone or ticlopidine alone in patients suffering transient ischemic attack or cerebral infarction. In 17, 24, and 23 patients, respectively, 300 mg/day aspirin, 200 mg/day ticlopidine, and 81 mg/day aspirin plus 100 mg/day ticlopidine were administered orally. Aspirin alone markedly inhibited platelet aggregation induced by arachidonic acid, partially inhibited platelet aggregation induced by adenosine diphosphate, and did not inhibit platelet aggregation induced by platelet activating factor. Ticlopidine alone inhibited platelet aggregation induced by adenosine diphosphate and platelet activating factor, but did not inhibit platelet aggregation induced by arachidonic acid. Combination therapy with aspirin plus ticlopidine markedly inhibited platelet aggregation induced by all three agonists. Plasma concentrations of beta-thromboglobulin and platelet factor 4 remained unchanged by aspirin alone, were slightly reduced by ticlopidine alone, and were markedly reduced by aspirin plus ticlopidine. Plasma concentration of thromboxane B2 was reduced by aspirin alone or with ticlopidine, but not by ticlopidine alone. The level of 6-ketoprostaglandin F1 alpha was reduced only by aspirin alone. Bleeding time was significantly prolonged by aspirin alone and by ticlopidine alone, although the greatest prolongation was produced by aspirin plus ticlopidine. Our results indicate that the combination of aspirin plus ticlopidine is a potent antiplatelet strategy, although the clinical importance of the changes observed need to be determined by a properly designed and controlled prospective study.
Stroke 1989 Dec
PMID:Combination therapy with low-dose aspirin and ticlopidine in cerebral ischemia. 253 43

We examined mitochondrial oxidative function 5 minutes and 2 hours after a gradual asphyxial insult in newborn lambs. We subjected 16 ventilated newborn lambs to 75-90 minutes of hypoxia and hypercarbia that resulted in bradycardia and systemic hypotension over the final 15 minutes of the insult. At the end of asphyxia, the lambs were resuscitated and returned to control ventilator settings. Samples of brain were removed 5 minutes (n = 8) and 2 hours (n = 8) after asphyxia. Each group of eight lambs was subdivided into those less than 3 or greater than 3 days old to evaluate the effect of age on postasphyxia mitochondrial function. After classification into nonsynaptic and synaptic mitochondria, mitochondrial respiration (oxygen consumption) was measured using five different substrates. Data from asphyxiated lambs were compared with that from a control group of ventilated nonasphyxiated lambs (n = 8). In the lambs less than 3 days old, there was significant depression of mean +/- SEM nonsynaptic mitochondrial state 3 (adenosine diphosphate-dependent) respiration to 29.5 +/- 5.2% of control with four of the five substrates and of state 4 respiration to 33.7 +/- 0.9% of control with three of the five substrates 5 minutes after asphyxia. By 2 hours after asphyxia, mean +/- SEM nonsynaptic mitochondria state 3 respiration increased to 70.4 +/- 6.4% of control while state 4 respiration increased to 58.2 +/- 4.5% of control. In contrast, lambs greater than 3 days old exhibited no inhibition of nonsynaptic mitochondrial function after asphyxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Stroke 1989 May
PMID:Mitochondrial function after asphyxia in newborn lambs. 271 9

PAF-acether, a naturally occurring phospholipid, is a potent activator of various biological processes, including platelet aggregation. The mechanisms of action of PAF are largely unknown. We have found that the psychotropic triazolobenzodiazepine drugs, alprazolam and triazolam, potently (IC50 less than 1 microM) inhibit PAF-induced shape change, aggregation and secretion of human platelets. These effects are specific for PAF-activation, since the responses of human platelets to other agonists (ADP, thrombin, epinephrine, collagen, arachidonate and the Ca++ ionophore, A23187) are not inhibited by these triazolobenzodiazepines. The action of triazolobenzodiazepines on PAF-induced platelet function has clinical relevance, especially in diseases where enhanced platelet aggregability may lead to thrombosis and atherosclerosis. In addition, the ability of triazolobenzodiazepines to inhibit other PAF-mediated cellular-responses, such as anaphylactic shock or bronchoconstriction, suggests that these drugs may be useful in preventing several known pathophysiological effects of PAF. The specific antagonism of PAF action by psychotropic drugs also suggests that PAF or PAF-like phospholipids may play a role in neuronal function. This possibility was tested by examining the effects of PAF on neural cells of the clonal line NG108-15, grown in culture in a chemically defined, serum-free medium. Low concentrations of PAF (0.5-2.5 microM) induced neurite extension in NG108-15 cells, whereas higher concentrations (greater than 3 microM) were cytotoxic. Using NG108-15 cells preloaded with aequorin, it was found that PAF causes an increase in intracellular ionized calcium concentration, which is dependent on the presence of extracellular calcium. These results suggest that PAF-induced Ca++ uptake may play a role in neuronal development, and that circulating PAF may contribute to the neuronal degeneration caused by the exposure of neural tissues to blood in situations such as spinal cord injury, trauma, or stroke.
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PMID:Interactions of the alkyl-ether-phospholipid, platelet activating factor (PAF) with platelets, neural cells, and the psychotropic drugs triazolobenzodiazepines. 289 25


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