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

This study examined the calcium dependency of contractions in arteries from rats made hypertensive by aortic coarctation and in rats with genetic hypertensive (stroke-prone spontaneously hypertensive rats). Mesenteric artery and aortic strips were suspended in tissue baths for isometric force recording and contractions to two drugs were characterized: 1) a phorbol ester, TPA (12-O-tetrade-canoylphorbol-13-acetate), and 2) the calcium channel agonist, Bay K 8644. Thoracic aortae and mesenteric arteries from hypertensive rats were more sensitive to the contractile properties of the protein kinase C activator TPA than comparable arteries from normotensive rats. In thoracic aortae from coarcted rats, the contractile activity of Bay K 8644 was potentiated compared to normotensive values. In the presence of 19.2 mmol/L KCl, responses to Bay K 8644 in thoracic aortae from normotensive rats were potentiated and did not differ from coarcted values. In contrast, contractions to Bay K 8644 and TPA in abdominal aortae obtained below the coarctation were not different from normotensive values. Upon exposure to 26.2 mmol/L KCl, contractions to Bay K 8644 in abdominal aortae were potentiated and those in aortae from coarcted rats did not differ from sham values. Contractile responses to both drugs were blocked by nifedipine and verapamil and responses were attenuated in calcium-free solution. We conclude that calcium channel function and its regulation by protein kinase C contribute to altered vascular reactivity in hypertension. Further, these abnormalities have a pressure dependency, because they did not occur in abdominal aortae from coarcted rats.
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PMID:Calcium and contractile responses to phorbol esters and the calcium channel agonist, Bay K 8644, in arteries from hypertensive rats. 169 54

Aggregation and secretion of washed platelets from stroke-prone spontaneously hypertensive rats (SHRSP) were greatly reduced by the development of the hypertension compared with those of platelets from age-matched normotensive Wistar-Kyoto rats (WKY). Concomitantly, thrombin-induced phosphorylation of the 47 kDa protein in SHRSP platelets was significantly decreased. However, TPA-induced aggregation, secretion and 47 kDa protein phosphorylation in SHRSP platelets were similar to those in WKY platelets. These results suggest that protein kinase C activity and its substrate were normally present in SHRSP platelets and that defects in the receptor-mediated activation of protein kinase C. This defective protein phosphorylation may be an underlying mechanism for the dysfunction of SHRSP platelets.
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PMID:Defects of thrombin-induced protein phosphorylation in platelets from stroke-prone spontaneously hypertensive rats. 394 26

Streptokinase remains the most widely used agent worldwide, largely because it is the cheapest. Because of cost considerations when the incremental cost of the use of accelerated TPA exceeds $35,000 (US) per life year added, and because an iatrogenically induced stroke in a patient who is otherwise likely to have a good outcome is unacceptable, streptokinase may be used in patients with small to moderate-sized infarctions and those aged less than 60 years. Streptokinase is the agent of choice in patients who have an increased risk of stroke and may be used in patients presenting after 6 hours. Streptokinase also may have a role in patients with cardiogenic shock. Administration of accelerated TPA is the treatment of choice in patients at high risk such as those with large anterior infarctions, the elderly, and patients with bypass grafts, and it is an alternative to urokinase when streptokinase has been administered previously. The most important approach is to treat as many patients as early as possible with thrombolytic therapy regardless of which agent is used. Thrombolytic therapy still is widely underused. More lives will be saved, regardless of which thrombolytic drug is used, by encouraging patients to present early, improving on the "door-to-needle" time, and treating more patients with a therapy that can save thousands of lives worldwide.
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PMID:Selecting a thrombolytic agent. 758 72

At present, data are available from three large-scale randomized trials of mortality that directly compared different thrombolytic regimens, namely, GISSI-2, ISIS-3, and GUSTO-1. These trials randomized over 100,000 patients worldwide. When examined individually as well as in aggregate, these trials demonstrate at most only small absolute differences between thrombolytic agents both in terms of lives saved and major complications, including hemorrhagic stroke. Specifically, TPA produces more strokes and cerebral bleeds, but whether or not there is a small incremental mortality benefit is not yet clear. All three trials indicate that the choice of thrombolytic agent is much less important to ultimate survival than is the delay time between onset of symptoms and initiation of treatment. Further, any potential differences in efficacy and safety between the available thrombolytic agents are unlikely to pertain to the majority of infarct patients who present to hospitals more than 4 h after the onset of symptoms. Since all three agents appear to be effective when given up to 12 h after the onset of symptoms, a clinical strategy must be adopted to increase thrombolytic utilization for late arrivers regardless of which agent is chosen. Patients excluded from thrombolytic therapy because of age, gender, presence of bundle-branch block on admitting electrocardiogram, and late arrival in the emergency department in fact benefit substantially from thrombolysis as long as contraindications to the drug do not exist. Nonetheless, only one-third of U.S. patients with acute myocardial infarction receive thrombolytic therapy, compared with over two-thirds of patients in the United Kingdom and several other European countries.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thrombolytic therapy: pre- and post-GISSI-2, ISIS-3, and GUSTO-1. 815 57

Thrombolytic therapy has been proposed in the treatment of cerebrovascular occlusive disease. Early clinical experiences with Urokinase and Streptokinase raised concern about the risk of hemorrhagic complications. More recently, tissue plasminogen activator (tPA) has been evaluated experimentally with promising results. Its clinical utilization has been recently initiated. A review of experimental and clinical data on thrombolysis in cerebral ischemia is presented. TPA treatment produced recanalization and clinical improvement in several patients. The rate of intracranial hemorrhagic complications is similar to the incidence of spontaneous hemorrhagic conversion of ischemic infarction. Nevertheless, large placebo-controlled clinical trials are necessary to further define the efficacy and the optimal modality of administration of tPA in thromboembolic stroke.
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PMID:Thrombolysis in cerebral ischemia. A review of clinical and experimental data. 830 72

With the discovery of new and effective acute stroke therapies, health care professionals now have the means to reverse the effects of an acute stroke. These advances must be aggressively applied to the acute stroke population using the EBR concept. It is clear from all of the issues and studies reviewed in this article that an organized approach and team concept are necessary for the efficient and effective care of acute stroke patients. Health care professionals currently treat acute myocardial infarction and trauma patients with a similar organization and sense of urgency. This paradigm should be translated and modified for the acute stroke population. Improved public and professional education are a vital part of this effort, and will have to be ongoing for its success. The approval of TPA as the first acute stroke therapy provides an opportunity to reverse the effects of a stroke. However, patients must present and be treated soon after stroke onset for this therapy to be safe and effective.
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PMID:Emergency brain resuscitation. 923 89

The GUSTO trial and an Australian consensus meeting in 1993 led to the recommendation that recombinant tissue plasminogen activator (r-TPA) was the preferred thrombolytic in patients with acute myocardial infarction (AMI) and ST segment elevation under the age of 75, whose infarction was anterior, who could be treated within four hours of the onset of symptoms and who did not have a contraindication to thrombolysis. Available data suggest that streptokinase (SK) should not be administered in a patient who has received this drug three days or more previously. New data on the risks of stroke confirm that the use of r-TPA is associated with a higher risk of intracranial haemorrhage than SK, and those with a high risk profile for intracranial haemorrhage (hypertension and advanced age) should receive SK rather than r-TPA. It may be justified to give r-TPA to any patient with a large infarct regardless of location, within four hours of the onset of infarction in an attempt to achieve TIMI flow grade 3 (complete) reperfusion, reduce mortality and improve left ventricular function and clinical outcomes. The focus for the future will be on how to treat more patients earlier with thrombolytic agents, rather than the choice of agent.
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PMID:Alteplase (r-TPA) vs streptokinase. 977 31

Cytidine and choline, present in cytidine 5'-diphosphate choline (CDP-choline), are major precursors of the phosphatidylcholine found in cell membranes and important regulatory elements in phosphatide biosynthesis. Administration of CDP-choline to rats increases blood and brain cytidine and choline levels; this enhances the production of endogenous CDP-choline which then combines with fatty acids (as diacylglycerol), to yield phosphatidylcholine. We examined the effect of providing cytidine and choline on incorporation of free fatty acids into phosphatidylcholine and other major phospholipids in PC12 cells. Addition of equimolar cytidine and choline (100-500 microM) to [3H]-arachidonic acid (50 microM, 0.2 microCi, bound to bovine serum albumin) dose-dependently increased the accumulations of [3H]-phosphatidylcholine (PtdCho), [3H]-phosphatidylinositol (PtdIno) and [3H]-phosphatidylethanolamine (PtdEtn) (by up to 27+/-3%, 16+/-3% and 11+/-3%, respectively, means+/-S.E.M.). This effect was seen with 8-18 h of incubation. The incorporation of [3H]-oleic acid into [3H]-PtdCho was even more enhanced (by up to 42+/-3%) as were the incorporations of [14C]-choline and [3H]-glycerol. The effects of choline and cytidine were enhanced by 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 microM), which activates CTP:phosphocholine cytidylyltransferase (CT) and facilitates choline uptake. Replacing choline by ethanolamine also enhanced the incorporation of [3H]-arachidonic acid into [3H]-PtdEtn, [3H]-PtdIno and [3H]-PtdCho. Arachidonic acid (10-200 microM) alone failed to affect the incorporation of [14C]-choline into phosphatidylcholine. We suggest that the increases in phospholipid synthesis caused by concurrent cytidine and choline supplementation enhance the incorporation of arachidonic acid and certain other fatty acids into the major glycerophospholipids. Removing these fatty acids as source of potentially toxic oxidation products could contribute to the beneficial effects of CDP-choline in treating stroke or other brain damage.
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PMID:Enhancement of free fatty acid incorporation into phospholipids by choline plus cytidine. 1008 83

Lot of advancement has taken place, not only in the management but also in the pathophysiology and imaging modalities in patients of stroke. Indolent chronic infections, particularly those due to H. pylori, have been identified as one of the risk factors. The mechanism of inflammation in inducing a precoagulant state has also been worked out. SPECT studies have detected ischaemic areas before appearance of CT abnormalities. CT angiography identifies abnormalities in the 'circle of willis' in posterior circulation strokes much better, and helps weigh the risk versus benefit of thrombolysis. With experiance in use of r-TPA, the list of contra indications and precautions has become longer than its indications. Newer drugs like lubeluzole and edselen have also been recommended. Various other drugs e.g. aptiganel hydrochloride, MDL 28170, 'basic fibroblast growth factor' and 'superoxide dismutase' are at an experimental stage. The concept of a 'stroke cocktail' may be in vogue soon. Controversies still exit regarding the exact indication of prophylactic anticoagulant and the 'international normalized ratio' (INR) to be achieved. Guidelines have been laid down for the approach to patients with asymptomatic carotid artery stenosis. However, the paramount message in stroke care is dissipation of the concept of 'brain attack', amongst the primary care medical and para-medical personnel.
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PMID:Ischaemic stroke: new frontiers. 1051 74

Reperfusion of intracranial arteries can be detected by transcranial Doppler (TCD). The authors report microembolic signals (MES) on TCD as a sign of clot dissolution and recanalization. Microembolic signals were detected during routine diagnostic TCD examination performed in the emergency room in patients eligible for thrombolytic therapy. Microembolic signals were found at the site of M1 middle cerebral artery (MCA) high-grade stenosis or near-occlusion. Transcranial Doppler was performed before, during, and after thrombolytic therapy. Of 16 consecutive patients, 3 (19%) had MES on TCD. All three patients had a severe MCA syndrome at 2 hours after stroke onset scored using the National Institutes of Health Stroke Scale (NIHSS). In patient #1 (NIHSS 12), clusters of MES were detected distal to a high-grade M1 MCA stenosis preceding spontaneous clinical recovery by 2 minutes. Because of subsequent fluctuating clinical deficit, intraarterial thrombolysis was given with complete recovery. In patient #2 (NIHSS 20), TCD detected an M1 MCA near-occlusion. At 1.5 hours after intravenous tissue plasminogen activator, TCD showed minimal MCA flow signals followed by MES, increased velocities, and normal flow signals in just 2 minutes. She gradually recovered up to NIHSS 8 in 5 days. In patient #3 with NIHSS 22 and an M1 MCA near-occlusion, TCD detected MES 15 minutes after TPA bolus followed by MCA flow velocity improvement from 15 cm/sec to 30 cm/sec. The patient recovered completely by the end of tissue plasminogen activator infusion. The authors conclude that embolic signals detected by TCD at the site of arterial obstruction can indicate clot dissolution. Intracranial recanalization on TCD can be associated with MES and changes in flow waveform, pulsatility, and velocity if insonation is performed at the site of arterial obstruction.
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PMID:Intracranial clot dissolution is associated with embolic signals on transcranial Doppler. 1066 79


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