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

Thromboxane synthetase activity is selectively inhibited by (E)-3-[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid hydrochloride monohydrate (OKY-046). A single dose of 100 mg OKY-046 was orally administered to patients with ischemic cerebrovascular disease and healthy volunteers. Platelet aggregation and thromboxane B2 (TXB2) generation of intact and homogenised platelets induced by 1.0 mM sodium arachidonate were measured before and at 1, 4, 6 and 8 h after dosing. OKY-046 inhibited arachidonate-induced aggregation in platelet rich plasma from some, but not all, individuals, whereas platelet TXB2 generation was almost completely inhibited by a single dose of 100 mg OKY-046, in all of the patients and healthy volunteers. Endogenous TXA2 and prostacyclin (PGI2) biosynthesis were assessed by measurement of urinary immunoreactive TXB2 (i-TXB2) and 6-keto-PGF1 alpha (i-6-keto-PGF1 alpha) before and at 0-3, 3-6, 6-9 h after dosing. OKY-046 increased the urinary i-6-keto-PGF1 alpha coincidently with a decrease of urinary i-TXB2, both in patients and healthy volunteers. These effects of a selective thromboxane synthetase inhibitor will improve a disturbed balance between TXA2 and PGI2, associated with the development of ischemic cerebrovascular disease.
Stroke
PMID:The effect of a thromboxane synthetase inhibitor, OKY-046, on urinary excretion of immunoreactive thromboxane B2 and 6-keto-prostaglandin F1 alpha in patients with ischemic cerebrovascular disease. 388 80

Thirty-two patients with acute cerebral infarction received either prostacyclin or placebo intermittently for 65 hours. Pulse and blood pressure were not altered by prostacyclin. After infusion there was no change in infarct volume or cerebral blood flow in either group. After normalisation for starting values, age and site of cerebral infarction there was a greater than 10% improvement in speech in the prostacyclin group, but minimal changes in neurological score or disability status. Age is related to neurological score at 14 days after stroke by decreasing improvement by 6.8% for each additional 10 years. This study has not been able to demonstrate that prostacyclin is effective in the treatment of ischaemic stroke, but due to the sample size the chance of proving this statistically (the power) was small. Similarly any conclusion that prostacyclin is not effective may be wrong because of the Type II error probability being high.
Stroke
PMID:Double-blind controlled trial of prostacyclin in cerebral infarction. 389 Feb 79

9 beta-Methyl carbacyclin (9 beta Me; ciprostene) is a synthetic, chemically stable analogue of prostacyclin (PGI2; epoprostenol). The platelet anti-aggregating and cardiovascular effects of 9 beta Me have been compared to PGI2 in anaesthetized monkeys and dogs. In addition, their haemodynamic effects have been compared in open-chest anaesthetized dogs and conscious dogs. Intravenous infusion of 9 beta Me and PGI2 to the anaesthetized monkey resulted in a dose-dependent hypotension, tachycardia and inhibition of ex vivo ADP-induced platelet aggregation. 9 beta Me was 72 times less active than PGI2 both as a hypotensive and anti-aggregating agent. Intravenous infusion of 9 beta Me and PGI2 to the anaesthetized beagle dog resulted in a qualitatively similar haemodynamic profile. Thus both substances induced a dose-dependent hypotension accompanied initially by a slightly increased heart rate, a dose-dependent increase in cardiac output, stroke volume and an increased peak LV dP/dt. At the higher doses studied, the initial increases in the parameters measured were succeeded by dose-dependent falls. 9 beta Me was 76 times less active than PGI2 as a hypotensive agent. In the anaesthetized greyhound, a dose-dependent anti-aggregating and hypotensive effect was seen with either drug, with 9 beta Me being 23 and 40 times less active than PGI2, respectively. Intravenous infusion of 9 beta Me and PGI2 to the conscious beagle dog induced a dose-dependent hypotension and a variable effect on heart rate. 9 beta Me was 33 times less active than PGI2 as an hypotensive agent. The duration of the hypotensive response induced by 9PMe was not significantly different from that induced by PGI2 in either monkey or beagle dog.
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PMID:The cardiovascular and platelet actions of 9 beta-methyl carbacyclin (ciprostene), a chemically stable analogue of prostacyclin, in the dog and monkey. 389 65

In a pilot study, 26 patients with acute completed strokes (48 hours to 5 days after cerebral infarction) were randomly assigned to the prostacyclin (PGI2) or placebo groups. PGI2 sodium salt (Epoprostenol, Wellcome Research Laboratories and Upjohn Company) or its solvent (glycine buffer) were infused into the subclavian vein for six-hour periods in five courses separated by six-hour intervals. Prostacyclin was administered at a rate of 2.5-5.0 ng/kg/min. A significant alleviation of neurological deficits occurred 6 and 54 hours after the treatment in patients receiving prostacyclin. This improvement lost its statistical significance at the end of a two-week observation period. It is concluded that further modified controlled studies are required to evaluate the therapeutic usefulness of PGI2 in the treatment of patients with cerebral ischaemia.
Stroke
PMID:Double-blind controlled trial of the therapeutic effects of prostacyclin in patients with completed ischaemic stroke. 390 21

This study investigates the interaction of thromboxane, prostacyclin, and the hemodynamic dysfunction of graded bacteremia. Arterial, venous, and pulmonary artery catheters were inserted into eight adult female pigs under barbiturate anesthesia. After a 60-min control period Aeromonas hydrophila (1.0 X 10(9)/ml) was infused intravenously at 0.2 ml/kg/hr, increasing gradually to 4.0 ml/kg/hr at 4 hr. Hemodynamic measurements, blood gases, and radioimmunoassay of thromboxane B2 (TxB) and prostaglandin 6-keto-F1 (PGI) were performed during the control period, at 10, 20, 30, 45, 60, 75, and 90 min of bacteremia and at 30-min intervals thereafter. During the bacterial infusion, cardiac index (CI), mean arterial pressure (MAP), paO2, pvO2, stroke volume (SV), and left ventricular stroke work (LVSW) decreased significantly, and pulmonary vascular resistance (PVR), pulmonary artery pressure (PAP), and intrapulmonary shunt (Qs/Qt) increased significantly. TxB was significantly increased at 30 min and remained elevated thereafter. PGI did not rise above control levels until after 240 min of bacterial infusion. TxB cross-correlated most frequently with CI, PVR, SV, paO2, and Qs/Qt, changes in TxB preceding the other variables by 0-60 min. PGI cross-correlated significantly with MAP, LVSW, CI, paO2, and Qs/Qt, changes in PGI preceding MAP, LVSW, and CI by 0-60 min, but following paO2 and Qs/Qt by 30-60 min. TxB is increased early in graded bacteremia and appears related to cardiorespiratory dysfunction. PGI increases late in graded bacteremia, following the onset of respiratory failure, and may mediate the arterial hypotension of septic shock.
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PMID:Thromboxane, prostacyclin, and the hemodynamic effects of graded bacteremic shock. 391 37

We tested the antiplatelet effects of low-dose aspirin in patients with occlusive cerebrovascular disease, because conventional dosage aspirin inhibits vascular synthesis of prostacyclin at the same time that it inhibits platelets. The effects on platelet function and thromboxane A2 synthesis of 40 mg of aspirin daily or 40 mg aspirin plus dipyridamole were measured in 23 patients starting within a week after the onset of cerebral ischemia. All patients had normal baseline platelet aggregation responses to four stimuli: arachidonate, epinephrine, adenosine diphosphate and collagen. The generation of thromboxane A2 by platelets, measured as serum thromboxane B2, was also normal. After 3 to 7 days of low dose aspirin therapy, platelet aggregation responses were suppressed to the extent observed with higher dosage aspirin. Serotonin release during platelet aggregation was inhibited by more than 95% and thromboxane B2 levels in clotted blood fell by more than 95%. Responses to aspirin treatment were similar in patients with transient ischemic attacks and in those with stroke and were also similar in both sexes. No differences in platelet responses were observed between patients receiving aspirin alone and aspirin plus dipyridamole. Thus 40 mg aspirin daily inhibited platelet responses as effectively as higher doses of aspirin in patients who had recent cerebral ischemia and showed a cumulative antiplatelet effect.
Stroke
PMID:Effects of low dose aspirin on platelet function in patients with recent cerebral ischemia. 396 66

The aim of this study was to determine the effect of ACTH-induced hypertension on the hemodynamic dose-response curves to intravenous infusion of prostacyclin (PGI2) in conscious sheep. PGI2 was infused for 10 minutes at doses of 0.05-0.50 micrograms/kg per min and hemodynamic dose-response curves were performed before, during and after ACTH-induced hypertension. Prior to ACTH administration prostacyclin infusions produced dose dependent decreases in mean arterial pressure (MAP), calculated total peripheral resistance (CTPR) and stroke volume (SV). These changes were accompanied by an increase in cardiac rate (CR) and cardiac output (CO). After five days of ACTH treatment MAP had risen from 72 +/- 1 to 91 +/- 2 mm Hg and infusions of PGI2 produced similar effects on MAP to those seen prior to ACTH. However the effects on CTPR, CO, SV and CR were all potentiated relative to normotensive animals. Three days after ACTH administration had ceased and basal pressure had returned to normotensive levels, the responses of CR, CO and SV to PGI2 infusions were similar to those seen prior to ACTH. However the exaggerated fall in CTPR seen during ACTH treatment was still present and this resulted in a very large decrease in MAP. These studies suggest that in this model of steroid-induced hypertension the resistance vessels are more sensitive to PGI2 and that the blood pressure response to PGI2 is regulated by different mechanisms to those seen prior to ACTH.
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PMID:The hemodynamic effects of prostacyclin infusions in normotensive and ACTH induced hypertensive conscious sheep. 609 93

We examined the effects of nifedipine, a calcium slow-channel blocking drug, on haemodynamics, blood gases, cardiac arrhythmias, and prostanoid release in anaesthetised greyhounds before, during, and after a 40-min occlusion of the left anterior descending coronary artery. Fifteen minutes after commencing treatment with nifedipine (5 micrograms/kg + 0.67 micrograms kg-1 min-1), there were significant reductions in arterial blood pressure, left ventricular end-diastolic pressure, and vascular resistance, with increases in cardiac output and stroke volume. Although coronary artery blood flow was unchanged, oxygen extraction was decreased, indicating that nifedipine reduced oxygen consumption. Nifedipine prevented the haemodynamic changes that occur in control dogs during acute myocardial ischaemia and markedly reduced the number of arrhythmias during coronary artery occlusion. The incidence of ventricular fibrillation induced by release of the occlusion was significantly reduced from 88% in the control group to 22% in the group receiving nifedipine. The release of thromboxane B2 and 6-keto PGF1 alpha (stable breakdown products of thromboxane A2 and prostacyclin, respectively) from the acutely ischaemic myocardium was not altered by nifedipine. It is concluded that this low dose of nifedipine had marked antiarrhythmic activity during both coronary artery occlusion and reperfusion. The relationship to dosage and possible mechanisms for this effect are discussed.
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PMID:Nifedipine reduces arrhythmias but does not alter prostanoid release during coronary artery occlusion and reperfusion in anaesthetised greyhounds. 619 Nov 39

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.
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PMID:Platelet structure and function role of prostaglandins. 624 76

1. The haemodynamic effects of short-term prostacyclin infusions (0.05-0.50 microgram/kg per min) were investigated in conscious adult sheep. 2. Haemodynamic dose-response curves to prostacyclin were performed before, during and after production of ACTH-induced hypertension. 3. Prior to ACTH administration prostacyclin produced dose-dependent reductions in mean arterial pressure, total peripheral resistance and stroke volume and these were accompanied by increased in heart rate and cardiac output. 4. After 5 days of ACTH-induced hypertension prostacyclin produced similar effects on mean arterial pressure to those seen prior to ACTH but the effects on heart rate, cardiac output, stroke volume and total peripheral resistance were markedly increased. 5. These studies demonstrate that the responsiveness of the circulation to prostacyclin is altered in ACTH-induced hypertension.
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PMID:ACTH hypertension modifies the haemodynamic effects of prostacyclin infusions in sheep. 625 3


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