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

The authors studied the interaction between red blood cells (RBCs) and prostacycline (P) in normal subjects and patients with transient disorders of the cerebral circulation and cerebral stroke. RBCs accelerated P disintegration with the formation of inactive products, with the process being most accelerated in RBC aggregation. It has been found that hyperosmolarity of the medium and disoxygenation of RBCs increase their ability to break down P while lactacydosis decreases this ability. It has been also established that there is a greater proportion of people with a marked ability of RBCs to break down P among patients with cerebral dyshemias, particularly with cerebral stroke. This might be due to alterations in the conformation of the surface layers of RBCs in abnormal conditions.
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PMID:[Effect of erythrocytes on the stability of prostacyclin in healthy subjects and patients with cerebral dyshemias]. 353 19

A new stable prostacyclin analog, OP-41483, was used in patients with severe congestive heart failure (CHF) due to coronary artery disease and compared with nitroprusside. During infusion of both drugs, mean brachial arterial pressure, total pulmonary resistance, pulmonary artery wedge pressure and systemic vascular resistance decreased significantly. Cardiac index and stroke index also increased significantly. Platelet aggregation did not change significantly during nitroprusside but decreased significantly with OP-41483 infusion. Thus, this analog may be useful for treatment of patients with CHF due to coronary artery disease.
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PMID:Vasodilator therapy with a new stable prostacyclin analog, OP-41483, for congestive heart failure due to coronary artery disease and comparison of hemodynamic effects and platelet aggregation with nitroprusside. 353 72

In a canine model of global brain ischemia, six dogs received a selective thromboxane A2 synthetase inhibitor, UK 38,485 (dazmagrel) before the ischemic event; six received a saline placebo. Cerebral blood flow (CBF), systolic and diastolic arterial pressure, cardiac output, pH, PaCO2, PaO2, and arterial and jugular-vein thromboxane B2 (a stable metabolite of thromboxane A2) and 6-keto PGF1 alpha (a stable metabolite of prostacyclin) were measured at baseline, after release of aortic and venae caval occlusion and at intervals up to 120 min thereafter. Treated animals showed nearly complete post-ischemic inhibition of thromboxane B2 production; control animals showed increases in jugular venous thromboxane B2. Arterial and jugular venous levels of 6-keto PGF1 alpha were significantly higher in treated animals at most post-ischemic intervals. CBF in both groups was similar to baseline values at time 0, then declined similarly in both groups by 30 min to approximately equal to 35% of baseline values where it remained thereafter. There were no significant differences in other variables at any interval. We conclude that inhibition of thromboxane A2 production does not alter post-ischemic brain hypoperfusion.
Stroke
PMID:Inhibition of thromboxane A2 production does not improve post-ischemic brain hypoperfusion in the dog. 354 49

The therapeutic efficacy of prostacyclin in nonhemorrhagic cerebral infarction was assessed in a placebo-controlled double-blind trial. A total of 80 patients with stroke onset within 24 hours were randomized into placebo (37 patients) and prostacyclin (43 patients) groups. Demographic data and risk factors were comparable. Patients in the prostacyclin group received a continuous i.v. infusion of prostacyclin at an average rate of 8.5 ng/kg/min for an average of 64 hours. The placebo group received vehicle only in a similar fashion. During treatment hemodynamic changes were more prominent in the patients receiving prostacyclin and included reduction of systolic and diastolic blood pressure and increase in pulse rate. In contrast there was only a slight (but significant) reduction of diastolic blood pressure in the placebo group. Neurologic deficit scores were determined on admission, at Day 3, and at Weeks 1, 2, and 4. Mean neurologic deficit scores upon entry were comparable in the placebo and prostacyclin groups, and a significant improvement in the score for neurologic deficit was noted in both. The placebo group tended to fare better throughout the study, with a significant difference in neurologic deficit score favoring the placebo group at Week 2 (p = 0.0048). Two patients in the placebo and one in the prostacyclin group died. The only difference in adverse reactions was flushing (6 patients in prostacyclin vs. 0 in placebo group, p less than 0.05). The results of this study suggest a lack of therapeutic efficacy of prostacyclin in a defined population of patients with nonhemorrhagic cerebral infarction.
Stroke
PMID:Intravenous prostacyclin in acute nonhemorrhagic stroke: a placebo-controlled double-blind trial. 355 Dec 12

Many strokes are thought to develop as a consequence of platelet aggregation on areas of arterial endothelial damage, with subsequent embolism or thrombus formation. Aspirin prevents platelet adhesion and aggregation by inhibiting the formation of thromboxane A2 by platelets. This suggests that aspirin could be used to prevent stroke. However aspirin also inhibits endothelial formation of the anti-aggregatory substance prostacyclin, though probably only in a slightly higher dose than that just capable of inhibiting platelet aggregation. Consequently, too high an aspirin dose may defeat its purpose. The effect of aspirin on platelets lasts for as long as they survive, whereas the effects of aspirin on endothelium are shorter. Theoretical considerations suggest that aspirin, given in brief pulses just to reach platelet inhibitory concentrations in plasma, and administered at the maximum interval that will maintain inhibition of platelet aggregation, should offer the most favourable balance between altered platelet and altered endothelial function from the viewpoint of stroke prevention. Data are presented showing that rapid rather than slow or delayed release aspirin preparations are necessary to achieve suitable plasma aspirin concentration-time profiles in humans, and that a peak plasma aspirin concentration of around 1.2 mg/L is necessary in vivo to inhibit aggregability of previously untreated platelets.
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PMID:The basis for aspirin dosage in stroke prevention. 366 79

Although laser endarterectomy has recently been suggested as useful in the treatment of arteriosclerotic obstructions, the "in vivo" clotting effects have not been well delineated. In this study, the common carotid and femoral arteries of ten mongrel dogs were exposed, and alternating 1 cm segments of each artery were treated with surgical endarterectomy and low-powered CO2 laser endarterectomy. Segments were then harvested, and subjected to histologic examination and vascular prostacyclin synthesis determinations, as measured by 6-keto PFG1a radioimmunoassay. Gross examination and light and scanning electron microscopy showed increased platelet aggregation and more extensive damaging of the underlying media of the laser compared to the surgical segments. Six-keto PFG1a levels were significantly lower (p = 0.001) in the laser compared to surgical sites (mean 232 +/- 72 pg/mg vs 515 +/- 144 pg/mg), or controls (895 +/- 337 pg/mg). These findings suggest that laser endothelial evaporation leads to increased thrombotic potential in the early post-operative period in comparison to surgical endarterectomy.
Stroke
PMID:Laser endarterectomy: a comparison of thrombotic potential following CO2 laser vs surgical endarterectomy. 375 58

Perinatal cerebral infarction, or stroke, is a not uncommon finding in newborns who survive after intensive care. Asphyxia, with its component parts hypoxemia and hypotension, represents the most common cause of perinatal cerebral infarction and may result in neuropathological changes in the periventricular white matter. Previous studies have demonstrated regional alterations in cerebral blood flow (CBF) in response to hypoxemic insult. This work examines the effects of hypoxemia on regional cerebral prostaglandin levels in the developing brain, since some observers believe that local CBF is controlled in part by prostaglandins. In this study, newborn beagle pups were anesthetized, subjected to tracheotomy and artificially ventilated to maintain normoxemia and normocarbia. Mean arterial blood pressure (MABP) was continuously monitored by means of an indwelling catheter and transducer, and craniectomies were performed. When the pups were physiologically stabilized, they were randomly assigned to receive acute hypoxemic insult (pO2 14.0 +/- 1.55 mm Hg, mean +/- standard deviation) accomplished by altering the oxygen concentration in the inspired air) or to receive no insult (mean pO2 84.3 +/- 13.0 mm Hg). Fifteen minutes following stable hypoxemic or normoxic conditions, all pups underwent in vivo freezing of the intracranial contents under anesthesia followed by rapid sacrifice. No significant differences were noted between the MABP, pH, or pCO2 values for the control and hypoxemic pups during the experimental period. Regional cerebral prostaglandin data demonstrated a significant increase in prostaglandin (PG)E2 in the gray matter of hypoxemic pups when compared to the normoxic controls (p less than 0.02). No significant differences were noted for 6-keto-PGE1 alpha, the stable metabolite of prostacyclin, or thromboxane (TX)B2, the stable metabolite of TXA2, in the gray matter. In addition, although 6-keto-PGE1 alpha was significantly lower in the periventricular white matter of the hypoxemic pups (p less than 0.05), there were no changes in the white matter in either PGE2 or TXA2. This regional differential synthesis of PGE2 in response to hypoxemic insult may explain the relative failure of CBF to the periventricular white matter and thus the neuropathological alterations attributed to it.
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PMID:Beagle puppy model of perinatal cerebral infarction. Regional cerebral prostaglandin changes during acute hypoxemia. 377 84

Thromboxane A2 and prostacyclin are two compounds which have been implicated as important modulators of local cerebral blood flow. Concentrations of the stable metabolites of these two compounds, thromboxane B2 and 6-keto-PGF1 alpha, were measured in cerebrospinal fluid (CSF) from eight acute ischaemic stroke patients and 14 patients with no evidence of cerebrovascular disease. Concentrations of thromboxane B2 ranged from 0.15 to 4.0 pg/ml and were significantly higher (P = 0.025) in the ischaemic stroke group when compared with the control group (0.1-0.3 pg/ml). Simultaneously acquired concentrations of 6-keto-PGF1 alpha were not elevated in the stroke group when compared to normals. These clinical findings support evidence from animal studies that emphasizes the importance of cerebral prostaglandins in mediating the secondary vascular changes of cerebral infarction. In conclusion there is an aberration in CSF thromboxane B2 concentrations in patients who have had a stroke. This may be an acute or chronic phenomenon.
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PMID:Prostanoid concentrations in human CSF following acute ischaemic brain infarction. 379 12

Endothelium of cerebral surface vessels (pial arterioles and venules) was injured with a light/dye technique in anesthetized mice. This induced platelet aggregation at the site of injury. The onset of aggregation was monitored through a microscope in mice given angiotensin II acetate, 4 micrograms i.v. 30 minutes earlier. Aggregation latency was compared with that in vehicle treated (saline) mice. Angiotensin II caused a highly significant delay in aggregation within the arterioles which was not related to a change in shear rate of blood. Angiotensin II added to platelet rich plasma, failed to influence the aggregation produced by subsequent addition of 0.5 microM ADP or 0.5 mM sodium arachidonate. Angiotensin is a well known stimulator of prostacyclin synthesis or release, and angiotensin has been reported to inhibit platelet aggregation ex vivo by increasing prostacyclin in the effluent superfusing the mass of aggregating platelets. Our data represent the first report of an antiaggregating effect of angiotensin II in vivo in an intact microvascular bed. The data is consonant with the literature describing increased prostacyclin levels following angiotensin II infusion. The antiaggregating effect of angiotensin in cerebral microvessels may help explain a recent observation describing increased survival of gerbils treated with angiotensin following carotid ligation.
Stroke
PMID:Angiotensin delays platelet aggregation after injury of cerebral arterioles. 381 Jul 22

Prostacyclin is a powerful vasodilator and inhibitor of platelet aggregation that has been implicated to play a role in cerebrovascular disease. Prostacyclin is unstable in aqueous solution and stabilized in serum by binding to an unidentified serum protein as measured by gel filtration. In 15 patients with ischemic stroke we measured the serum prostacyclin binding capacity and the rate of degradation of exogenously added prostacyclin. There was a significant reduction in serum prostacyclin binding capacity and a significant increase in rate of degradation in the patients with ischemic stroke as a whole compared to controls, and in patients with persistent deficits. Decreased serum prostacyclin binding capacity and accelerated rate of prostacyclin degradation in vitro, may reflect an accelerated rate in vivo of prostacyclin degradation, thereby increasing susceptibility to stroke. Since only a small number of patients were investigated, the findings are of a preliminary nature and must be confirmed by further studies with large numbers of patients and appropriate patient controls.
Stroke
PMID:Reduction of serum prostacyclin stability in ischemic stroke. 388 Sep 46


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