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

The thromboxane A2-receptor antagonistic properties of Bay U 3405 [(3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9-carbaz o-lepropanoic acid] have been evaluated in various pharmacologic models. Bay U 3405 specifically inhibits platelet aggregation induced by U 46619, collagen, platelet-activating factor, and the second wave of ADP (IC50 0.5, 0.07, 0.3, 0.19 microM) in human plasma. The plasma phase of ADP-induced aggregation is not affected. U 46619-induced platelet aggregation is competitively antagonized (pA2 = 6.3). In humans, ex vivo platelet aggregation is inhibited after oral application of 2 or 50 mg Bay U 3405. Bay U 3405 also specifically and competitively antagonizes U 46619-induced contractions of rabbit aortic rings (pA2 = 7.4). In vivo, Bay U 3405 protects rabbits dose dependently from arachidonic acid or collagen-induced thromboembolism (ED50 1-3 mg/kg p.o). Chronic administration of Bay U 3405 to stroke-prone spontaneously hypertensive rats reduces stroke-related mortality and diminishes the occurrence of cerebral hemorrhages. From these results, we conclude that Bay U 3405 is an orally active, selective, and competitive thromboxane A2-receptor antagonist that may be beneficial in the treatment of cardiovascular or cerebrovascular diseases.
Stroke 1990 Dec
PMID:Characterization of Bay U 3405, a novel thromboxane A2/endoperoxide receptor antagonist. 214 34

Intracranial bleeding is an important cause of brain masses and edema. To study the pathophysiology of intracerebral hemorrhage, we produced experimental hemorrhages in 53 rats and characterized the lesion by histology, brain water content, and behavior. Adult rats had 2 microliters saline containing 0.5 unit bacterial collagenase infused into the left caudate nucleus. Histologically, erythrocytes were seen around blood vessels at the needle puncture site within the first hour. By 4 hours there were hematomas, the size of which depended on the amount of collagenase injected. Necrotic masses containing fluid, blood cells, and fibrin were seen at 24 hours. Lipid-filled macrophages were observed at 7 days and cysts at 3 weeks. Water content was significantly increased 4, 24, and 48 hours after infusion at the needle puncture site and for 24 hours in posterior brain sections. Behavioral abnormalities were present for 48 hours, with recovery of function occurring during the first week. Brain tissue contains Type IV collagen in the basal lamina. Collagenase, which occurs in an inactive form in cells, is released and activated during injury, leading to disruption of the extracellular matrix. Collagenase-induced intracerebral hemorrhage is a reproducible animal model for the study of the effects of the hematoma and brain edema.
Stroke 1990 May
PMID:Collagenase-induced intracerebral hemorrhage in rats. 216 Jan 42

Bay U 3405 [(3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9- carbazolepropanoic acid] potently inhibits platelet aggregation, thromboxane A2-induced contraction of smooth muscles, and coronary artery thrombosis. We have previously demonstrated inhibition of arachidonic acid-induced sudden death by Bay U 3405. The purpose of this study was to investigate the effects of Bay U 3405 on thromboembolism provoked by collagen. Collagen fibrils dissolved in an isotonic glucose solution were injected into a marginal ear vein of anesthetized rabbits. Sudden death occurred within a few minutes due to elevated thromboxane A2 levels causing intravascular platelet aggregation and myocardial ischemia. In the vehicle-treated group, 100% of the animals died. One of the most prominent parameters was the massive fall in blood pressure. All animals pretreated with 10 mg/kg orally Bay U 3405 survived, showing only a transient hypotensive effect. Tracings of the electrocardiogram and heart rate were unchanged. Bay U 3405 will therefore be useful to elucidate the role of thromboxane A2 in various cardiovascular and respiratory diseases.
Stroke 1990 Dec
PMID:Effect of Bay U 3405, a new thromboxane antagonist, on collagen-induced thromboembolism in rabbits. 226 Jan 39

The natural history of amaurosis fugax with hemodynamically insignificant degrees of internal carotid artery stenosis is uncertain. Seventy-three patients over age 40 who presented with amaurosis fugax without obvious cause and had ipsilateral stenoses of 50% or less with carotid duplex scanning were followed for a mean period of 35.5 months (range 3-110) without surgical intervention. At the initial vascular laboratory duplex evaluation, 35 patients had normal arteries (47.9%), 29 had minor (0-19%) stenoses of the ipsilateral internal carotid arteries (39.7%), and 11 had 20-50% stenosis (15.1%). Four patients with 0-19% stenosis and one patient with 20-50% stenosis experienced a subsequent stroke or permanent ipsilateral blindness. When analyzed by life-table format, stroke, blindness, and early death were more frequent in patients with minor degrees of stenosis than in those with normal arteries. Investigations in all patients with amaurosis fugax should be aimed at identifying whether the symptoms are explained by arteriosclerotic, systemic, collagen, cardiac, hematologic, or ophthalmologic disease. When no other etiology is found, and localized carotid bifurcation atherosclerosis of even modest degrees is identified, an atheroembolic etiology should be considered.
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PMID:The natural history of amaurosis fugax with minor degrees of internal carotid artery stenosis. 229 74

We describe two patients with cerebrovascular complications of Ehlers-Danlos syndrome type IV. A 16-year-old girl with spontaneous internal carotid artery dissection and a 46-year-old woman with aneurysmal subarachnoid hemorrhage and multiple aortic dissections were both deficient in collagen type III, analyzed in cultured skin fibroblasts. To our knowledge, spontaneous carotid artery dissection associated with collagen type III deficiency has not been reported previously. Early clinical recognition of this syndrome is of great importance in view of the hazards of angiography and surgery. Collagen type III deficiency plays a role in the pathogenesis of intracranial saccular aneurysms and may also be involved in the pathogenesis of carotid cavernous fistulas and dissections of the cervical arteries.
Stroke 1990 Apr
PMID:Cerebrovascular disease in Ehlers-Danlos syndrome type IV. 198 66

To determine whether the duration of hypertension is an essential component in the evolution of myocardial dysfunction, renal artery constriction was performed in male Fischer 344 rats at 4 months of age, and in vivo global cardiac performance of sham-operated and experimental animals was evaluated 8 months later. Systemic arterial blood pressure increased to 173 +/- 5 mm Hg 2 weeks after the arteries were clipped and remained elevated for the following 5 months. Blood pressure decreased over the remaining 3 months to a value not significantly different from control rats that were killed, 132 +/- 4 mm Hg. After 8 months of renovascular hypertension, we observed that the elevated level of systolic arterial pressure was accompanied by a distinct absence of left ventricular hypertrophy when measured at the ventricular weight level. Moreover, left ventricular end-diastolic pressure increased in hypertensive animals from 6.0 to 24.0 mm Hg while peak left ventricular pressure was identical to controls. In addition, peak +dP/dt and -dP/dt were depressed in hypertensive animals. Although stroke volume was unaltered, cardiac output in renal artery clipped animals was depressed by 34% while total peripheral resistance was elevated by 50%. Ventricular chamber remodeling in the hearts of hypertensive animals was evidenced as a 19% increase in the transverse and a 16% increase in the longitudinal axes of the left ventricle with a 27% diminution of wall thickness. Myocardial damage, in the form of myocyte loss and replacement fibrosis, increased in the hearts of hypertensive animals resulting in a ninefold augmentation in the volume fraction of collagen within the ventricular wall. These alterations in the architectural properties of chamber geometry coupled with the abnormalities in contractile performance resulted in a severe reduction in ejection fraction from 82% to 47% and a marked elevation in transmural diastolic and systolic stress in hypertensive animals. The gradient in stress across the ventricular wall, from epicardium to endocardium, revealed a direct correlation with the regional distribution of myocardial damage. In conclusion, the loading state of the myocardium, tissue injury, and myocardial fibrosis all appear to be critical determinants in the genesis of left ventricular failure in long-term pressure overload.
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PMID:Left ventricular failure induced by long-term hypertension in rats. 233 33

The hemodynamic and myocardial effects of chronic treatment (5 months) with converting enzyme inhibitor (CEI, enalapril, group T1, n = 10) or a beta 1 blocker (atenolol, group T2, n = 13) of normotensive mature male Wistar rats were studied and compared to untreated younger rats (group C0, 11 months old, n = 14) and to untreated age-matched controls (group C1, 16 months old, n = 14). Heart rate was significantly decreased in T2 rats but unchanged in the T1 group. There was a significant decrease in systolic and diastolic arterial blood pressure (BP) in both treated groups (systolic T1:90 +/- 17, T2: 87 +/- 10, vs. C1: 102 +/- 11 mm Hg, and diastolic T1: 60 +/- 17, T2: 59 +/- 9, vs. C1: 73 +/- 13 mm Hg). Cardiac output was unchanged by therapy but stroke volume was significantly increased in the T2 group (0.24 +/- 0.03 vs. 0.19 +/- 0.04 cm3 in C1). Total peripheral resistance was significantly decreased in T1 and T2 groups. Left ventricular weight to body weight ratio (LVW/BW) was significantly decreased in T1 (1.74 +/- 0.11 vs. 2.02 +/- 0.22 in C1) but unchanged in T2 (1.90 +/- 0.15 vs. 2.02 +/- 0.22). The left ventricular passive pressure-volume curve was significantly rightward shifted by beta-blocker therapy (T2) but unchanged by CEI (T1). This corresponds to a decrease of chamber stiffness k in the T2 group compared to C1 and T1 groups. A significant fibrosis was seen in group T2 (mean collagen fiber thickness of 3.03 +/- 0.24 vs. 2.8 +/- 0.15 micron) but not in the T1 group (2.94 +/- 0.14 vs. 2.8 +/- 0.15 micron). Thus, despite the similar decrease in BP induced by the CEI and the beta blocker, the cardiac effects of the two drugs were opposite: CEI decreased LVW/BW with no change in the left ventricular pressure-volume curve and myocardial fibrosis whereas beta blocker did not change the LVW/BW, but induced a left ventricular dilation associated with a decrease in chamber stiffness and an increase in subendocardial fibrosis.
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PMID:Long-term cardiac effects of hypotensive agents in normotensive mature rats: comparison of beta-blocking agent and converting enzyme inhibition. 247 16

We studied 23 patients suffering cerebral ischemia who also had laboratory evidence of either a lupus anticoagulant (LA) or an abnormal anticardiolipin antibody (ACA). Four patients had lupus or a lupus-like illness, three had drug-induced lupus, and 16 had no overt evidence of collagen-vascular disease. Cerebral ischemic events were multiple in 71% of the patients; two patients presented with multi-infarct dementia. Recognized cerebrovascular disease risk factors were present in 57% of the patients. The partial thromboplastin time was prolonged in only 35% of the patients. An LA was identified in 15 of 21 patients tested, and an elevated ACA titer was identified in 10 of 12 patients tested. Simultaneous assays for LA and ACA were discordant in eight of 10 patients tested. LA- and ACA-associated brain ischemia is often recurrent, but other risk factors for cerebrovascular disease are often present. The laboratory findings in such patients may display considerable heterogeneity.
Stroke 1989 Feb
PMID:Lupus anticoagulants, anticardiolipin antibodies, and cerebral ischemia. 249 72

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

To study the pathogenesis of platelet activation in ischemic stroke, ionized calcium ([Cai2+]) was measured in aequorin-loaded gel-filtered platelets in the basal and stimulated state. Basal [Cai2+] was increased in stroke patients maximally 36-72 hours after onset. The increase in [Cai2+] after stimulation with thrombin, collagen, and platelet-activating factor were also greater in stroke patients, but the profiles of these [Cai2+] changes were parallel to control. Cross incubation of control platelets with plasma from stroke patients resulted in raised basal [Cai2+] and caused the release of serotonin from platelets. These results indicate that the higher platelet basal [Cai2+] in stroke patients represents a lowered threshold for activation and that this may be due to a plasmatic factor rather than a primary platelet defect.
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PMID:A plasmatic factor may cause platelet activation in acute ischemic stroke. 258 96


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