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

Activities of aortae to produce prostaglandin (PG) I2-like substance in stroke-prone spontaneously hypertensive rats (SHRSP), stroke-resistant SHR (SHRSR) and normotensive control rats from the Wistar-Kyoto (WK) colony were compared. PGI2-like substance was produced by the incubation of the aortic ring in pH 9.0 borate-buffered saline and the amount produced was estimated by comparison of its anti-aggregatory activity with that produced by known amounts of the sodium salt of synthetic PGI2. Before the development of stroke, amounts of this substance generated in SHRSP and SHRSR were significantly higher than those in WK rats (p less than 0.01 and p less than 0.02, respectively). Remarkably reduced capacity to generate PGI2-like substance was observed in some SHRSP after the development of stroke.
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PMID:Production of prostacyclin-like substance in stroke-prone and stroke-resistant spontaneously hypertensive rats. 3 17

Local application of prostacyclin (PGI2) to cerebral (pial) microvessels, inhibited the aggregation of platelets induced in the vessels by exposing them to a filtered mercury light source following intravenous sodium fluorescein. The inhibition was consistantly observed in venules rather than arterioles and was manifest by a lengthening of the time required for the noxious stimulus to produce an initial aggregate, and/or by a lengthening of the time required for enlarging aggregates to totally block the venule. The consistency of the inhibition diminished at doses below 100 microgram/ml. Inhibition was observed whether or not alcohol was used as the vehicle for PGI2 and whether or not the body temperature of the anesthetized mouse was permitted to fall.
Stroke
PMID:Topical prostacyclin (PGI2) inhibits platelet aggregation in pial venules of the mouse. 38 37

Twenty-seven heparinized dogs were exposed to 35 min of cerebrospinal fluid compression ischemia followed by 30 min of recirculation. The degree and distribution of post-ischemic reperfusion was then assessed by means of a 14C-antipyrine autoradiographic blood flow study. The animals were assigned to 5 groups by the administration of drugs as follows: 1) no additional drugs; 2) indomethacin 1.5 or 4 mg/kg prior to ischemia; 3) indomethacin 4 mg/kg 5 min after ischemia; 4) prostaglandin I2 (PGI2) infusion 30--180 ng/kg/min beginning 5 min after ischemia; and 5) indomethacin 4 mg/kg 5 min after ischemia plus PGI2 infusion 30--130 ng/kg/min beginning 5 min after ischemia. Animals receiving no additional drugs had relatively low post-ischemic blood flows with focal zones of greatly impaired reperfusion. Animals receiving either indomethacin or PGI2 after ischemia did not differ significantly from the no additional drug group. A significant enhancement of post-ischemic reperfusion occurred in animals receiving indomethacin prior to ischemia and those receiving the combination of indomethacin and PGI2 after ischemia. These observations implicate an imbalance in prostaglandin pathways at the blood-endothelial interface in the genesis of post-ischemic reflow impairment and suggest novel drug therapy for enhancing nutrient flow after ischemia.
Stroke
PMID:Prostaglandin I2 and indomethacin prevent impairment of post-ischemic brain reperfusion in the dog. 39 21

Prostaglandins participate in the regulation of blood pressure in normotensive and hypertensive subjects; vascular tone is subject to the continuous relaxing influence of endogenous vasodilating prostaglandins. Prostaglandin I2 (PGI2; prostacyclin), probably the most important physiological modulator of vascular tone, decreases blood pressure together with a concomitant increase in cardiac output and a reduction in systemic vascular resistance secondary to peripheral vasodilation. In addition, vasodilation within the splanchnic, pulmonary and coronary vascular beds has been observed, with increased blood flow through the mesenteric, renal and coronary vascular beds. These changes in regional blood flow have been associated with the inhibition, by PGI2, of the vasoconstrictor response to sympathetic nervous stimulation and pressor hormones [noradrenaline (norepinephrine), angiotensin II]. However, other prostaglandins, such as prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha), induce coronary vasoconstriction and have different effects on pulmonary artery blood pressure because of their effect on pulmonary vascular resistance. Nonsteroidal anti-inflammatory drugs (NSAIDs; e.g. indomethacin) have been reported to induce hypertension parallel to a fall in cardiac output, suggesting that the underlying mechanism is an increase in systemic vascular resistance. In animal models these agents reduced regional blood flow in the ischaemic myocardium, with a corresponding increase in infarct size. Ibuprofen, which inhibits prostaglandin synthesis to a lesser extent than indomethacin, did not exert systemic or coronary haemodynamic effects. NSAIDs also provide protection in shock models but may exacerbate haemodynamic derangements and decrease survival in acute hypovolaemic hypotension. To what extent do NSAIDs and opioids influence cardiovascular status during the postoperative course and analgesic therapy? Continuous infusion of NSAIDs for analgesia had no major haemodynamic effects. Also, there were insignificant changes in indices of left heart function (cardiac output, stroke volume) and the systemic circulation (mean arterial pressure, systemic vascular resistance) following intravenous ketorolac injections, whereas cardiac output and mean arterial pressure decreased after administration of morphine. The pulmonary circulation was unaffected by ketorolac administration, whereas morphine administration induced an increase in pulmonary vascular resistance. Indices of right and left cardiac work were decreased by morphine. Thus, ketorolac produces fewer haemodynamic effects than morphine, although it is possible that some of the effects of morphine may result from morphine-induced histamine release. NSAIDs may be seen as a worthwhile gain with respect to morphine in clinical situations when hypotension is disadvantageous or when reduction in afterload is not a specific therapeutic aim.
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PMID:Cardiovascular risks and benefits of perioperative nonsteroidal anti-inflammatory drug treatment. 128 61

Endothelium exerts an important influence on cerebral vascular tone through the production and release of a diverse group of vasoactive factors. Relaxing factors produced by endothelium include nitric oxide (or a nitric oxide-containing compound), a hyperpolarizing factor, and prostacyclin. Endothelium-derived contracting factors include cyclooxygenase products of arachidonic acid and endothelins. Several pathophysiological conditions are associated with increased formation of endothelium-derived contracting factors. Such endothelial dysfunction in the cerebral circulation may shift the balance of vascular tone toward constriction and may potentially contribute to the onset or maintainance of cerebral ischemia and stroke.
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PMID:Regulation of the cerebral circulation by endothelium. 129 44

By means of the radioimmunologic method changes of concentration of 6-keto-prostaglandin F1 alpha (PGF1 alpha)--the stable metabolite of prostacyclin in the rat brain have been evaluated during 5-min clinical death and up to 2 hrs after resuscitation. Ischemia did not produce significant changes of 6-keto-PGF1 alpha concentration in the brain. In the early postresuscitation period the concentration of 6-keto-PGF1 in the and 7-fold control values. Later the concentration of 6-keto-PGF1 alpha in the brain decreased reaching in 30 min a 3-fold the control level, and in 60 and 120 min after resuscitation control values. The reasons of unsuccessful therapy of ischemic stroke with prostacyclin are discussed.
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PMID:Changes in endogenous prostacyclin in the rat brain during clinical death and after resuscitation. 129 27

We evaluated the effects of beraprost Na (Sodium (+-)-(1R*,2R*, 3aS*,8bS*)-2,3,3a,8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3- hyd roxy-4-methyl-1- octen-6-ynyl]-1H-cyclopenta[b]benzofuran-5-butylate, beraprost), a stable and orally active prostacyclin (PGI2) analog with potent antiplatelet and vasodilating properties, on two stroke models, namely sudden death induced by arachidonate (AA) in rabbits and spontaneous stroke in stroke-prone spontaneously hypertensive rats (SHRSP). In the AA-induced sudden death model, 30 min after beraprost administration (1 or 3 mg/kg, po), AA was injected into the rabbit internal carotid artery, and incidence of convulsion and sudden death were assessed. Beraprost decreased both incidence of convulsion and mortality of rabbits. In SHRSP, orally administered beraprost (100 micrograms/kg, twice a day from 56-385 d of age) improved survival rate and decreased incidence of stroke. Preventive effects of beraprost on the two stroke models may have been caused mainly by the improvement of cerebral circulation. These results indicate that beraprost may have potential in the treatment and/or prevention of the cerebral circulatory disorders.
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PMID:The effects of beraprost Na, a stable prostacyclin analog, on animal models of stroke. 138 52

Severe necrotizing pancreatitis is accompanied by release of hemorrhagic ascites fluid (HAF), which is thought to be related to the occurrence and frequency of cardiocirculatory and pulmonary failure as a consequence of acute pancreatitis. The purpose of this study was to evaluate the role of HAF due to these systemic complications. Experiments were performed in 25 pigs (mean b.wt. 22 +/- 1 kg) under general anesthesia and mechanical ventilation. The animals received 50 ml/kg b.wt. i.p. of either physiologic saline solution (control CO, n = 9) or hemorrhagic ascites fluid (HAF, n = 16). HAF was obtained from 16 pigs with pancreatitis induced by intraductal infusion of bile salt. Eight animals in the HAF group were pretreated with indomethacin (10 mg/kg i.v. INDO/HAF). All animals were followed up for 6 h. Mean arterial pressure, cardiac output, and stroke volume fell significantly in the HAF (-25%, -27%, -27%) and in the INDO/HAF groups (-24%, -20%, -17%) as compared with controls (-6%, -6%, -6%). Also, left ventricular end-diastolic pressure (LVEDP) decreased by 52% and 48% in both HAF recipient groups, whereas LVEDP was unchanged in the control group. Myocardial contractility (Vmax) remained unaltered in all experimental groups. No significant differences in gas exchange and lung dry/wet weight ratio were observed. Lipase and PGI2 of the unpretreated HAF group rised to 203% and 198% in arterial blood at 6 h compared with unaltered levels in the control group. No increase of prostanoid concentrations was detected in the indomethacin-pretreated group, whereas lipase increase by a comparable extent as in the HAF group. We conclude that the early consequences of HAF are mainly characterized by systemic hypotension due to hypovolemia.
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PMID:Hemodynamic effects following intraperitoneal infusion of pancreatic ascites fluid. 141 Aug 1

We examined whether the renal protective effect of the angiotensin I converting enzyme inhibitor enalapril in stroke-prone spontaneously hypertensive rats (SHRSP) is dose-related and associated with alterations in the urinary excretion of prostaglandin (PG) E2 and 6-keto-PGF1 alpha, a stable breakdown product of prostacyclin. Enalapril maleate at 1.5, 5 and 15 mg/kg/day or vehicle was chronically administered to saline-drinking SHRSP (six per group) starting at 8.1 weeks of age. Vehicle-treated SHRSP developed severe hypertension, proteinuria and strokes (age at death, 14 +/- 1 weeks; mean +/- S.E.). Enalapril prolonged survival dose-dependently and reduced proteinuria; all SHRSP given 15 mg/kg/day lived beyond 23 weeks of age without evidence of stroke or proteinuria. There was no effect of enalapril at any dose on systolic arterial blood pressure in spite of variable levels of urinary protein excretion and onset of stroke in the different groups. Likewise, urinary 6-keto-PGF1 alpha and PGE2 excretion did not differ among the groups except for an increase in 6-keto-PGF1 alpha in the 15 mg/kg/day group at one week after initiation of enalapril therapy. These results are consistent with a dose-related renal protective action of enalapril in saline-drinking SHRSP that is not closely associated with sustained alterations in urinary excretion of renal vasodilatory PGs.
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PMID:The antiproteinuric action of enalapril in stroke-prone spontaneously hypertensive rats is unrelated to alterations in urinary prostaglandins. 154 1

Antiphospholipid antibodies provide a model for immune-mediated thrombosis. Study of the pathophysiological effects of antiphospholipid antibodies has revealed several potential thrombotic mechanisms. Experiments designed to elucidate these mechanisms have used both in vitro and in vivo techniques. Results implicate endothelial anticoagulant dysfunction, abnormalities of prostacyclin, antithrombin III, placental anticoagulant protein, proteins C and S, and complement activation, any of which could lead to thrombosis. In an individual patient, thrombosis may result from a combination of these abnormalities or it may require the presence of other nonimmune-mediated perturbations of the coagulation system.
Stroke 1992 Feb
PMID:Antiphospholipid antibodies: origin, specificity, and mechanism of action. 156 68


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