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

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

Aspirin inhibits thromboxane A2 and prostaglandin formation in platelets and prostaglandin I2 (prostacyclin) in vascular cells. It prevents platelet aggregation by irreversible acetylation of cyclooxygenase, a key enzyme in the arachidonic acid metabolism. Oral aspirin can be extensively hydrolyzed to inactive salicylate in the stomach and the liver (first-pass) before it enters the systemic circulation. Presystemic acetylation of platelets thus occurs during aspirin absorption, with a concomitant sparing of peripheral vascular cyclo-oxygenase, mainly exposed to salicylate. On the basis of its antiplatelet effect, aspirin has been assessed during the past two decades in patients with a history of myocardial infarction, stroke, transient ischemic attack or unstable angina. A meta-analysis of randomized controlled trials of long term aspirin treatment for secondary prevention of vascular disease indicated that aspirin (300-1500 mg daily) significantly reduced fatal and non-fatal vascular events. More recently aspirin (160 mg daily) produced a significant reduction in hospital vascular mortality and in non-fatal events in patients with suspected acute myocardial infarction. Combination of aspirin with streptokinase was significantly better than either drug alone. On the other hand two primary prevention trials of aspirin in healthy doctors did not show any modification of vascular mortality despite an overall reduction of non-fatal myocardial infarction. Resolution of some problems related to the mechanism of action of aspirin and to selection of trial populations will possibly increase the benefit/risk ratio of aspirin treatment for prevention of vascular disease.
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PMID:Aspirin as an antithrombotic drug: from the aggregometer to clinical trials. 215 Jul 36

We compared responses to calcium ionophore A23187, vasopressin, and substance P in helical strips of dog middle cerebral, basilar, and posterior communicating arteries to obtain a better understanding of humoral control of cerebrovascular tone in different brain regions and its potential impact on mechanisms of cerebral vasospasm. A23187 relaxed these different arterial strips partially precontracted with prostaglandin F2 alpha to a similar extent. Vasopressin produced concentration-dependent relaxation in basilar and posterior communicating arterial strips, whereas middle cerebral arterial strips either contracted or relaxed slightly. Relaxations induced by A23187 and vasopressin were either abolished or converted to contractions by removal of the endothelium. In contrast, the relaxation of cerebral arterial strips to substance P was markedly attenuated but not abolished by endothelium denudation; the remaining relaxation was suppressed by indomethacin. In some cerebral arterial strips with intact endothelium, substance P caused a transient contraction that was reversed to a relaxation by indomethacin or ONO-3708, a prostaglandin antagonist. In arterial strips denuded of endothelium from the same dogs, substance P always produced relaxations. Relaxations of cerebral arterial strips to A23187 and vasopressin appear to be mediated by endothelium-derived relaxing factor. The function of vasopressin receptors in endothelial cells differs markedly in basilar and posterior communicating arteries versus middle cerebral arteries. Substance P-induced relaxations appear to be primarily associated with endothelium-derived relaxing factor and with prostaglandin I2, whereas contractions appear to be mediated by endothelium-derived prostaglandins.
Stroke 1988 Nov
PMID:Endothelium-dependent and -independent responses to vasodilators of isolated dog cerebral arteries. 246 Sep 77

We exposed helical strips of dog middle cerebral arteries to oxyhemoglobin for 5 hours, rinsed them with bathing medium, and stored them overnight; we compared the responses of strips thus treated with the responses of strips without oxyhemoglobin treatment. Relaxation induced by nicotine was abolished by hexamethonium and was markedly inhibited after exposure to oxyhemoglobin. A low concentration of KCl (5 mM) elicited relaxation that was abolished by ouabain and significantly reduced by oxyhemoglobin. Endothelium-dependent relaxation caused by calcium ionophore A23187 was attenuated, and that caused by substance P was reversed to contraction after exposure to oxyhemoglobin. Contraction elicited by substance P also depended on endothelium and was abolished by indomethacin. Relaxation induced by TRK-100, a stable analogue of prostaglandin I2, was moderately attenuated by oxyhemoglobin. On the other hand, concentration-dependent relaxation induced by papaverine and contractile responses to KCl, serotonin, and prostaglandin F2 alpha were not affected by oxyhemoglobin. Our results indicate that vasodilations mediated by vasodilator nerves, the electrogenic sodium pump, endothelium-derived relaxing factor, and prostaglandin I2 were impaired in dog cerebral arteries exposed to oxyhemoglobin. After exposure to oxyhemoglobin, vascular endothelium appears to participate in cerebroarterial contraction via a release of vasoconstrictor prostaglandins. These actions of oxyhemoglobin may be involved in the genesis of cerebral vasospasm after subarachnoid hemorrhage.
Stroke 1989 May
PMID:Prolonged exposure to oxyhemoglobin modifies the response of isolated dog middle cerebral arteries to vasoactive substances. 247 Jan 67

Seven anesthetized dogs treated with prostaglandin I2, indomethacin, and heparin were compared with 12 controls to test the hypothesis that the salutary effect of treatment on recovery of neuronal function and cerebral blood flow (CBF) after ischemia is coupled to the inhibition of platelet accumulation. In this model of right hemisphere multifocal ischemia, cortical somatosensory evoked response (CSER) amplitude, 14C autoradiographic blood flow, and 111In-labeled platelet accumulation were measured. The ratio of injured to noninjured hemispheric 111In activity (cpm/g) provided an index of platelet accumulation. Treatment improved CBF of the injured hemisphere compared with control after 4 hours of reperfusion (74 +/- 17 versus 53 +/- 13 ml/100 g/min, p less than 0.05), and it enhanced recovery of CSER amplitude (percent of baseline) after 1 hour of reperfusion compared with control (27.1 +/- 4.7% [treatment] versus 15.5 +/- 2.8% [control], p less than 0.05). However, the effect on CSER was not sustained after 4 hours of recovery. Despite these effects on CSER and CBF, treatment failed to inhibit 111In-labeled platelet accumulation in the injured hemisphere (1.7 +/- 0.3% [treatment] versus 1.5 +/- 0.1% [control], p greater than 0.05). Platelets may adhere to damaged endothelium despite aggressive platelet antiaggregant therapy.
Stroke 1988 Jun
PMID:Effects of prostacyclin, indomethacin, and heparin on cerebral blood flow and platelet adhesion after multifocal ischemia of canine brain. 328 1

Forty-five conditioned male mongrel dogs were exposed to multifocal ischemia sufficient to maintain suppression for 60 minutes of the P1-N1 amplitude of the cortical sensory evoked response (CSER), a quantifiable index of neuronal function. Ischemia was induced and regulated by successive embolization of 20 to 50 microliters increments of air via the right internal carotid artery. Subsequently, the P1-N1 amplitude recovery of the CSER was followed for an additional 15, 60, or 120 minutes while the dogs were treated or left untreated. The combination of prostaglandin I2 (PGI2), indomethacin, and heparin promoted a statistically significant augmentation of return of CSER amplitude relative to no treatment, PGI2 alone, indomethacin alone, PGI2 and heparin, indomethacin and heparin, or PGI2 and indomethacin. After 60 minutes of recovery, animals receiving combined PGI2, indomethacin, and heparin achieved a 57% recovery of P1-N1 amplitude relative to baseline, while the corresponding recoveries in all other groups clustered around 20%. By 120 minutes of postischemic follow-up, the CSER recovery induced by PGI2, indomethacin, and heparin was 80% compared to 17% in untreated animals. By 15 minutes into the recovery period, the combination of the three agents had eliminated very low flows in the "neuron-disabling" range (defined as 0 to 15 ml/100 gm/min for gray matter and 0 to 6 ml/100 gm/min for white matter) in contrast to the relative inefficacy of no treatment or treatment with other than the triple combination of drugs. The study lends some support to a planned clinical trial of PGI2, indomethacin, and heparin in acute occlusive stroke in humans.
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PMID:Prostaglandin I2, indomethacin, and heparin promote postischemic neuronal recovery in dogs. 675 Dec 13

Defibrotide, a polydeoxyribonucleotide, has been found to modulate endothelial cell function, causing an increase in tissue plasminogen activator (t-PA) levels, a decrease in plasminogen activator inhibitor (PAI) levels, and an increase in prostaglandin I2 (PGI2) formation in humans. Defibrotide has no direct anticoagulant effect but has a synergistic action with heparin. A strong antithrombotic effect has been observed in animal models. Thus, defibrotide has a beneficial effect in cases of deep venous thrombosis (DVT), peripheral obliterative vascular disorder (POVD), stroke, vasculitis, and thromboembolism. Defibrotide also inhibits platelet function and activation. A significant decrease in platelet aggregate formation on the suture line in microarterial anastomosis in rats is one way defibrotide can inhibit platelet function and activation. In humans, a slight prolongation' of the lag period in collagen-induced aggregation has been observed. In addition, a slight decrease in the maximum amplitude of the secondary wave of ADP and adrenalin-induced aggregations was also found. Platelet adhesion is diminished, the platelet differential count on formvar membrane is altered, and platelet aggregate formation is significantly inhibited. With an increase in platelet cyclic AMP (cAMP) content and a decrease in malonyl dialdehyde (MDA) and thromboxane B2 (TXB2) formation, the levels of platelet secretion products such as PF-4 and beta-thromboglobulin (beta-TG) in plasma decreased progressively. It was also demonstrated that the 14C-glucose transport defect of the platelet membrane of atherosclerotic patients was partially corrected with defibrotide treatment.
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PMID:Effect of defibrotide on platelet function. 880 24

1. Prostacyclin elicits potent vasodilation and inhibition of platelet aggregation through binding to its membrane receptor. The impairment of prostacyclin receptor activity is implicated in various human cardiovascular diseases. We recently succeeded in molecular cloning of cDNA for the mouse, rat, and human prostacyclin receptors. 2. In the present study, we examined the mRNA expression of the prostacyclin receptor in various rat tissues, and further investigated its gene expression in the hypertrophied cardiac ventricles of stroke-prone spontaneously hypertensive rats (SHRSP). 3. In rat tissues, a single RNA band of approximately 3.7 kb was detected by northern blotting analysis using rat prostacyclin receptor cDNA as a probe. In adult Wistar rats, abundant mRNA expression was observed in the aorta, lung and spleen. Substantial amounts of transcript were expressed in the heart, pancreas, thymus and stomach. In contrast, no mRNA expression was detected in the brain. 4. We further examined the mRNA expression of the prostacyclin receptor in the ventricles of 21 week old SHRSP. The ventricles of SHRSP showed remarkable hypertrophy, compared with those of age-matched Wistar-Kyoto (WKY) rats. The expression of prostacyclin receptor mRNA in the hypertrophied ventricles of SHRSP was almost equivalent to that in the ventricles of WKY. 5. The present study revealed the gene expression of the prostacyclin receptor in various rat tissues, and further demonstrated the receptor mRNA expression in hypertensive cardiac hypertrophy. The present study will give a clue to investigate the clinical implication of prostacyclin and its receptor.
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PMID:Gene expression of prostacyclin receptor in the hypertrophied heart of spontaneously hypertensive rats. 907 86

We investigated the protective effect of chronic treatment with AE0047, a dihydropyridine-type calcium channel blocker, on vascular endothelial abnormalities in stroke-prone spontaneously hypertensive rats (SHRSP). Ten-week repeated antihypertensive treatment with AE0047 inhibited blood pressure elevation and improved endothelium-dependent relaxation in response to acetylcholine in aorta isolated from SHRSP. Furthermore, the abnormal production of prostaglandin I2 and thromboxane A2 in the aorta was normalized to a level equivalent to that in Wistar-Kyoto rats. These results suggest that chronic treatment with AE0047 exerts protective effects against endothelial abnormalities associated with the development of hypertension.
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PMID:Protection against endothelial abnormalities by a novel calcium channel blocker, AE0047, in stroke-prone spontaneously hypertensive rats. 1021 83

The neuroprotective effect of a central type prostacyclin receptor ligand was examined in a rat model of focal cerebral ischemia. Under halothane anesthesia, male Sprague-Dawley rats were subjected to left middle cerebral artery occlusion. A selective central type prostacyclin receptor ligand, 15-deoxy-(16-m-tolyl)-17,18,19,20-tetranorisocarbacyclin methylester, or a peripheral type prostacyclin receptor ligand, iloprost methylester, were administered intravenously immediately after ischemia. Twenty-four hours after ischemia, brain damage was evaluated. In separate experiments, concentrations of 15-deoxy-(16-m-tolyl)-17,18,19,20-tetranorisocarbacyclin in ischemic brain tissue were measured by injection of a tritium labeled compound. Treatment with 15-deoxy-(16-m-tolyl)-17,18,19,20-tetranorisocarbacyclin methylester (0.03 mg/kg) significantly (P<0.05) reduced the volume of brain damage by 35%. With this treatment, the concentration of this compound in the brain was more than 10 nM. Treatment with iloprost methylester did not show a neuroprotective effect. These results indicated that activation of a central type prostacyclin receptor attenuates ischemic brain damage. The present study demonstrated that the intravenous application of a central type prostacyclin receptor ligand could be a novel therapeutic agent for acute stroke.
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PMID:Specific ligand for a central type prostacyclin receptor attenuates neuronal damage in a rat model of focal cerebral ischemia. 1179 66


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