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

The present study was performed in 34 patients with transient cerebral ischemia, TCI. Twenty-four of the patients were examined angiographically. Atherosclerotic abnormalities were demonstrated in 13 and a total occlusion of the interior carotid artery was found in one patient. The angiograms were normal in 10 patients. One patient suffered from hyperlipoproteinemia, type IV, and one from diabetes mellitus. The platelet aggregation in vitro was increased significantly, as more patients than normal controls showed secondary aggregation with low ADP-concentration: less than or equal to 1 mumol (p less than 0.001). The fibrinolytic capacity was significantly reduced (p less than 0.01) but not particularly in the patients with increased tendency for platelet aggregation. No correlation found between changes in platelet aggregation, the fibrinolytic activity and the angiographic findings. The results described may favor the concept that a prophylactic use of drug excerting an antiaggregation effect on platelets might be useful in patients suffering from TCI.
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PMID:Platelet aggregation and fibrinolytic activity in transient cerebral ischemia. 84 81

Adenosine diphosphate (8 mg per minute for five minutes) was infused into the carotid artery of 63 rabbits. The effects were twofold: systemic hypotension and platelet aggregation in the cerebral circulation. As a consequence of the last effect, platelet emboli were produced which occluded cerebral arteries in a number and size sufficient to cause cerebral ischemia. Areas of focal ischemia were observed through a cranial window, and documented with antipyrine autoradiography. Platelet thrombi were almost entirely transient, being fragmented and removed within a very short time of cessation of ADP infusion. Consequently, no permanent tissue damage ensued. This experimental model approaches the spontaneous transient ischemia attacks (TIAs) in man, demonstrating that these can be caused by pure platelet emboli. A high cholesterol diet administered for two months prior to ADP infusion did not enhance the effect of the procedure or make the platelet aggregation and the following ischemia longer in duration or more severe.
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PMID:Animal model of TIA: an experimental study with intracarotid ADP infusion in rabbits. 119 26

A 49-year-old man had for 30 years suffered from severe recurrent thromboembolism with leg-vein thrombosis, pulmonary emboli, mesenteric infarction, cerebrovascular accident, cerebral vein thrombosis, portal vein thrombosis and femoral artery occlusion requiring leg amputation. In addition to moderately increased clotting activation with single-fold positive demonstration of fibrin monomers and a D-dimer concentration of 1 mg/l platelet aggregation was increased and could not be influenced by aspirin, 300 mg daily. Despite aspirin there were recurrent transitory attacks of cerebral ischaemia. Fibrin monomers were threefold positive and D-dimer concentration was increased to 4 mg/l (elevated clotting activation). Ticlopidine administration (250 mg daily) reduced adenosine diphosphate-induced platelet aggregation by 30% without effect on collagen-induced platelet aggregation. In parallel to these changes the patient's general condition clearly improved: fibrin monomers were no longer demonstrated and the D-dimer level fell to 0.5 mg/l.
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PMID:[Recurrent thromboembolism due to increased acetylsalicylic acid-resistant platelet aggregation]. 188 75

As an approach to understanding the molecular basis of the pathophysiology of cerebral ischemia, we examined qualitative and quantitative changes in pertussis toxin substrates, Gi1 and G0, in the membrane of rat cerebral cortex after decapitation. Within 1 min after decapitation, the extent of pertussis toxin-catalyzed [32P]ADP ribosylation of the G proteins in the cerebral cortex membrane was significantly decreased and the magnitude of the decrease became slightly larger upon further incubation of the decapitated brain. Addition of guanine nucleotides, GTP and GDP, or the purified beta gamma subunits of transducin to the membranes of control and ischemic cerebral cortex stimulated [32P]ADP ribosylation of the G proteins. The stimulation of [32P]ADP ribosylation in the control situation by guanine nucleotides was almost to the same extent as that in ischemia. However, the stimulation by transducin beta gamma subunits was different; the control stimulation was greater than that in ischemia. In immunoblots probed with antibodies against Gi1 alpha, G0 alpha, and T beta, the immunoreactivity of the corresponding proteins in ischemia was similar to that in control, suggesting that the amounts of G proteins were not changed in ischemia. These results suggest that ischemia accelerates the dissociation of alpha-GDP-beta gamma to alpha-GDP and free beta gamma and causes the denaturation of the dissociated alpha-GDP, thereby decreasing [32P]ADP ribosylation.
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PMID:Ischemia of rat brain decreases pertussis toxin-catalyzed [32P]ADP ribosylation of GTP-binding proteins (Gi1 and G0) in membranes. 189 6

We studied adenosine diphosphate-induced platelet aggregation and the associated release of thromboxane B2 in 49 patients with subarachnoid hemorrhage in relation to angiographic vasospasm. Postoperative cerebral angiography was performed less than or equal to 3 (median 1) days after surgery for an aneurysm 5-14 days after subarachnoid hemorrhage. Correspondingly, one sample from each patient was taken within 24 hours either before or after angiography. The occurrence of severe as well as diffuse, moderate, or severe angiographic vasospasm was associated with the presence of delayed cerebral ischemia (p less than 0.05). Patients with diffuse angiographic vasospasm had significantly higher (p less than 0.05) values for thromboxane B2 release than the others, even after adjustment by the clinical grades on admission and before surgery, the timing of surgery, the time from subarachnoid hemorrhage to angiography and blood sampling, and nimodipine therapy. Severe and diffuse angiographic vasospasm were also associated with poor outcome at 1 year (p less than 0.05). Our results suggest that augmented release of platelet thromboxane may be involved in the pathogenesis of vasospasm in large cerebral arteries.
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PMID:Angiographic vasospasm and release of platelet thromboxane after subarachnoid hemorrhage. 202 74

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

1. A possible cerebroprotective effect of a chemically stable prostacyclin analogue, beraprost sodium, was investigated in a canine model of cerebral ischaemia. Cerebral ischaemia was produced by the combined occlusions of the left subclavian and the brachiocephalic arteries with preceding ligations of the intercostal arteries. 2. The decrease in baroreceptor reflex sensitivity (BRS), measured by phenylephrine-induced reflex bradycardia, following 5 min ischaemia was used to assess the cerebroprotective effect. 3. Beraprost (1 microgram kg-1 min-1 i.v., infused for 15 min just before ischaemia) completely prevented the decrease in BRS. Although the lower dose of beraprost (0.1 microgram kg-1 min-1 i.v.) failed to show such a protective effect, its inhibitory effect on ADP-induced platelet aggregation was as potent as that of the higher dose. 4. The extent of decrease in BRS was inversely correlated with the extent of the residual blood flow in the medulla oblongata during ischaemia. Since beraprost did not affect the extent of the residual blood flow during ischaemia, its cerebroprotective effect could not be ascribed to the reduction of the degree of ischaemia by increasing collateral blood flow to the brain. 5. Post-ischaemic reduction of the regional blood flow in the medulla and the cerebral cortex was completely prevented by the higher dose of beraprost. 6. The present study suggests that the cerebroprotective effect of beraprost may be independent of its anti-aggregatory and vasodilator effects. It is possible that the protection may be due to a prostacyclin-like cytoprotective effect through membrane stabilization.
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PMID:Protective effect of beraprost sodium, a new chemically stable prostacyclin analogue, against the deterioration of baroreceptor reflex following transient global cerebral ischaemia in dogs. 211 14

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.
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PMID:Effect of nimodipine on platelet function in patients with subarachnoid hemorrhage. 239 64

We tested the hypotheses that after complete cerebral ischemia, first, rate of recovery of ATP, phosphocreatine (PCr), and intracellular pH (pHi) varies with ischemic duration and second, rate of metabolic recovery is a more sensitive predictor of consequent electrophysiological deficit than steady-state metabolic recovery. With the use of transient intracranial hypertension in anesthetized dogs, ischemic duration was set for either 3, 12, or 30 min, which depressed somatosensory-evoked potential (SEP) recovery amplitude by 30, 59, and 88%, respectively. In contrast, ATP, PCr, and pHi, measured by 31P magnetic resonance spectroscopy, fully recovered. When ischemic duration was increased from 3 to 12 min, mean recovery time of ATP (6 min) remained rapid but that of pHi (12-28 min) was prolonged. After 30 min of ischemia, pHi recovery was not slowed further (25 min) but that of ATP was now markedly prolonged (36 min). PCr recovery time increased progressively with ischemic duration (5, 11, and 21 min, respectively) and correlated best with SEP recovery (r = 0.74). We conclude that the brain's ability to rapidly normalize pH is a sensitive predictor of electrophysiological recovery after short ischemia but that ATP regeneration becomes important with prolonged ischemia. PCr recovery rate was the best overall predictor, probably because it depends on both pHi and the ratio of ATP to ADP by the creatine kinase reaction.
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PMID:Postischemic recovery rate of cerebral ATP, phosphocreatine, pH, and evoked potentials. 251 29


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