Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacological actions of iprazochrome (IC) on the vascular system were studied, and the following results were obtained: No death nor abnormal behaviors were observed in acute toxicity tests conducted on male and female mice and rats despite the administration of large doses of IC (10,000 mg/kg, p.o. and 80 mg/kg, i.v., respectively). IC inhibited dose-dependently platelet aggregation in vitro induced by arachidonate and ADP, whereas no effect was observed on ADP-induced respiratory depression in mice, which is closely related to platelet aggregation in vivo. The antiserotonergic actions of IC on the isolated external carotid arteries and femoral arteries in dogs observed in a noncompetitive manner were found to be 1/24 to 1/65 that of methysergide. On the other hand, IC showed no inhibitory effect on the paw edema of rats in vivo induced by serotonin. The inhibitory effect of IC on peritoneal dye leakage in mice was less than half that of phenylbutazone. IC prevented apoplexy in stroke-prone SHR (SHRSP) without lowering the blood pressure. Histological changes in the cerebrum of SHRSP were ischemic changes such as swelling of the neurons and shrinkage of the nuclei, mainly in the cerebral cortex and corpus striatum area.
 ...
PMID:[Pharmacological actions of iprazochrome on the vascular system]. 404 70

Stroke was induced in stroke-prone spontaneously hypertensive rats (SHRSP) by NaCl loading. They were killed at 3 weeks and cerebral lesion was confirmed by autopsy. About 2/3 of them had strokes. Platelet count and thrombin-induced aggregation were reduced to 36% and 66%, respectively, compared with the level of those in the healthy SHRSP group which did not have stroke with the same treatment. ADP and serotonin content in platelets diminished by 45% and by 65%, respectively, due to stroke while plasma thiobarbituric acid reacting substances (TBARS, lipid peroxides) in the stroke group was two-fold that in the healthy group. Blood TBARS levels were significantly higher in rats with lower platelet serotonin content than in rats with normal serotonin content. These results suggest that marked activation of platelets has occurred due to vascular injuries at the time of stroke with a consequent decrease in platelet serotonin content and increase in plasma TBARS.
 ...
PMID:The appearance of "exhausted" platelets at the time of stroke in stroke-prone spontaneously hypertensive rats. 408 11

The effects on central hemodynamics and skeletal muscle metabolism during surgery for abdominal aortic aneurysm were compared in 6 patients given a preoperative adrenergic block (group B) and in 6 patients who additionally had a temporary brachio-femoro-femoral by-pass during the aortic clamping (group B + S). The cardiac output, heart rate, arterial and pulmonary artery pressures and the cardiac filling pressure were studied. Biopsy specimens from the lateral vastus muscle and blood samples from the radial artery and the iliac vein were taken before aortic clamping and also before and 30 minutes, 4 and 16 hours after the aortic declamping. Intramuscular temperature and pH were measured. The glycogen, glucose, lactate, pyruvate, ATP, ADP, AMP, phosphocreatine (PCr) and creatine (Cr) contents of the muscle and the lactate and pyruvate concentration in iliac venous and radial arterial blood were determined, using enzymatic fluorometric techniques. In group B, aortic clamping induced severe temporary incomplete ischemia with a 300% increase in lactate/pyruvate (L/P) ratio and a fall in intramuscular pH (pHm). The adenylate energy charge (EC) decreased, but the creatine (PCr + CR) and the adenylate (ATP + ADP + AMP) pool remained unchanged. After aortic declamping, the L/P ratio, EC and pHm regained their preclamping values, but the pools of energy phosphate compounds were reduced, indicating dysfunction or damage of the muscle cells. In group B + S there were no major muscle metabolic changes during clamping or after declamping of the aorta. In group B the systemic vascular resistance (SVR), mean arterial blood pressure (MAP) and left ventricular stroke work (LVSW) increased during the occlusion. On release of the clamp, cardiac output rose, possibly due to the sudden reduction of SVR. A temporary marked fall of MAP occurred. In group B + S, no increase of SVR, MAP or LVSW was observed during aortic clamping. After the declamping, only a minor MAP drop was observed. In both groups, a brief rise in pulmonary vascular resistance after the aortic declamping suggested transient pulmonary microembolism. If a high-risk patient is to undergo reconstructive surgery of the abdominal aorta and/or technical difficulties can be expected to necessitate prolonged cross-clamping during the operation, a temporary extracorporeal by-pass may be a favorable adjuvant, improving cardiac performance and preventing derangement of muscle metabolism.
 ...
PMID:Temporary incomplete ischemia of the legs induced by aortic clamping in man. Metabolic and hemodynamic effects of temporary extracorporeal by-pass. 613 73

A long way has been travelled since platelets were likened to sponges in 1961. At that time research on thrombotic mechanisms was mainly concentrated on blood coagulation. Since then, a shift of emphasis toward the study of platelets has dramatically evolved. How to prevent platelets from becoming sticky at sites of injury has been the main concern for platelet researchers over the past decade. Following adherence of platelets to a damaged vessel wall, prostaglandin synthesis is triggered leading to the formation of thromboxane A2, the most potent platelet activating agent so far discovered. By an "autocatalytic" process, thromboxane A2 together with the released ADP are responsible for the growth of the platelet thrombus. Among the substances released by the alpha-granules is the mitogenic factor, which, by stimulating the proliferation of smooth muscle cells from the media to intimal layers in arteries, is instrumental in the generation of atherosclerotic plaques. The narrowing of the vessel wall lumen can be further aggravated by the formation of a thrombus over the plaque, thereby occluding the vessel, and leading to cardiovascular diseases or stroke depending on the location of the lesion. An all-out effort to find a means for preventing platelet stickiness is currently under way. The recent discovery of prostacyclin has been the cornerstone for most of the research carried out so far in this field. The presently available antiplatelet drugs should be used with caution. Indeed, whereas a dramatic thrombosis may occur with full platelet activation, a catastrophic hemorrhage may follow the "neutralization" of platelets. Eskimos who are fed with eicosapentaenoic acid, the precursor of a potent antiplatelet agent, may indeed be immune against thrombotic disorders; however, they have an increased tendency to bleed.
 ...
PMID:Platelet structure and function role of prostaglandins. 624 76

Rats were subjected to a 30 minute period of combined hypoxia (F1o2 = .08) and hemorrhagic hypotension (MAP = 30 mm Hg), then resuscitated by restoration of F1o2 = .30 and reinfusion of shed blood and saline. Intracranial blood volume, hemoglobin saturation, and the cytochrome alpha, alpha 2 redox state were monitored through the intact skull during hypoxic hypotension and after resuscitation utilizing reflectance spectrophotometry. Although resuscitation returned arterial blood pressure, arterial pO2, and hemoglobin saturation toward normal, a sustained, significant (p less than .005) reduction in cytochrome alpha , alpha 2 remained. A parallel series of rats was subjected to identical hypoxic hypotension. At designated intervals the animals were sacrificed to determine brain ATP, ADP, and inorganic phosphate (P1). The data are discussed in terms of relationships between high energy phosphate metabolism and recorded changes in cerebral cytochrome alpha , alpha 2 redox state.
Stroke
PMID:Failure of brain cytochrome alpha , alpha 3 redox recovery after hypoxic hypotension as determined by in vivo reflectance spectrophotometry. 627 81

Platelet aggregability and fibrinolytic activity were studied repeatedly in 83 patients with reversible cerebral ischemic attacks over a median follow-up period of 26 months. Platelet hyperaggregability, defined as in vitro secondary aggregation obtained by adenosine diphosphate concentration less than or equal to 1 mumol/l, was demonstrated in 36.1% or the patients examined 5-8 days after the attack, but only in 6% of age- and sex-matched blood donors (p less than 0.001). Fibrinolytic activity was reduced in 57.8% of the patients, as compared with 20.5% of the controls. At the time of follow-up only 8% of the survivors showed platelet hyperaggregability, whereas the fibrinolytic activity was still reduced in 44.4%. Over the observation period 21.7% of the patients had a stroke or died. No significant correlation was found between abnormalities of platelet aggregability or of fibrinolytic activity, when observed 5-8 days after the ischemic episode, and the subsequent risk of stroke or death. It is concluded that in patients with recent cerebral ischemic attacks the demonstration of platelet hyperaggregability or reduced fibrinolytic activity appears to be without prognostic significance.
 ...
PMID:Prognostic value of in vitro measurements of platelet aggregability and fibrinolytic activity in patients with reversible cerebral ischemic attacks. 636 86

The aggregation properties of washed SHRSP platelets were investigated in comparison with normotensive WKY platelets at prehypertensive (4 weeks), early hypertensive (11 weeks) and late hypertensive (17 weeks) ages in the absence of plasma factors. The number of platelets in SHRSP was markedly lower with the development of hypertension than that in WKY. The thrombin- and collagen-induced aggregation was markedly reduced in the platelets from 11 and 17 week old SHRSP compared with that of age-matched WKY, whereas the degree of platelet aggregation in 4 week old SHRSP showed a tendency to be even greater than that in WKY. The changes in blood pressure and platelet aggregability were correlated inversely. ADP did not induce aggregation in the same system used for thrombin and collagen stimulation but in another system it aggregated washed rat platelets. Aggregation responses to ADP and ionophore A23187 were also significantly lower in 14 week old SHRSP platelets than age-matched WKY platelets. Together with other evidence, these results suggest that defective Ca2+ function, rather than the presence of exhausted platelets, is responsible for hypoaggregability in SHRSP platelets.
Stroke
PMID:Hypoaggregability of washed platelets from stroke-prone spontaneously hypertensive rats (SHRSP). 642 Sep 47

The potential efficacy of the calcium channel blocker verapamil in modifying ischemic brain injury was evaluated in anesthetized rats subjected to 60 or 90 min of diffuse forebrain ischemia produced by bilateral occlusion of the carotid and vertebral arteries. Treated animals received verapamil, 2 mg/kg intravenously, prior to ischemia. Four hours of postischemic recirculation was permitted by reversing the carotid occlusions. Intermittent high-voltage slow-wave activity was noted on electroencephalograms shortly after verapamil infusion, prior to ischemia. The ischemic insult induced an isoelectric EEG, which tended to persist during recirculation in both treated and untreated animals. Similarly, verapamil pretreatment failed to influence brain water content or cerebral energy metabolites (phosphocreatine, ATP, ADP, AMP) or cerebral energy charge when assayed after four hours of recirculation. Thus, verapamil failed to confer a protective effect on brain electrical activity, water content, or energy metabolites following ischemia in this model.
Stroke
PMID:Verapamil: failure of metabolic amelioration following global forebrain ischemia in the rat. 643 33

Employing optical density methods, platelet aggregation in response to increasing concentration of ADP was tested in 24 patients with migraine and 15 controls. The migraine patients don't demonstrate platelet hyperaggregability when compared with controls. Platelet aggregate ratio (P.A.R.) was measured in 13 patients and 15 controls by the method of Wu and Hoak: a significant difference was found between and controls. The hyperaggregability found here, even if only for the P.A.R., may help explain the increased incidence of stroke and heart attack in migraine patients that has been reported elsewhere.
 ...
PMID:[Platelet aggregation in vasomotor headache]. 646 67

A trial was performed on thirty-two patients with cerebrovascular disease (transient ischaemic attack and stroke) to assess the effect of ticlopidine, a new inhibitor of platelet aggregation, on some platelet functions and coagulation, and its safety in long-term use (6 months). The results show that ticlopidine was highly effective in inhibiting ADP-induced platelet aggregation, platelet adhesiveness and circulating platelet aggregates, but it had no effect on fibrinogen levels. No serious side-effects were observed. Ticlopidine may therefore prove to be a useful antiplatelet drug in the management of patients with cerebrovascular disease.
 ...
PMID:Effects of long-term ticlopidine treatment on platelet function and its tolerability in cerebrovascular disease. 650 Jan 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>