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

Using the middle cerebral artery occlusion model in cats, we evaluated the possible role of the cyclooxygenase pathway in alterations of local cerebral blood flow and the development of cortical edema following prolonged ischemia or recirculation. We divided 57 cats into three groups, and each cat received saline (control), indomethacin, or the free radical scavenger ONO-3144. Each group was subdivided into prolonged ischemia (4 hours of occlusion: PI) and recirculation (2 hours of occlusion followed by 2 hours of recirculation: RC) subgroups. We compared local cerebral blood flow and cortical specific gravity between the PI and RC subgroups of the control and drug-treated groups. In the PI subgroup, indomethacin did not influence the time course of local cerebral blood flow but significantly worsened the decrease in cortical specific gravity. On the other hand, indomethacin significantly improved postischemic hypoperfusion and ameliorated the decrease in cortical specific gravity in the RC subgroup. The effects of ONO-3144 were similar to those of indomethacin, except that ONO-3144 did not affect cortical specific gravity in the PI subgroup. Indomethacin inhibits cyclooxygenase activity, whereas ONO-3144 scavenges the oxygen-centered radical released in the conversion of prostaglandin G2 to prostaglandin H2. Thus, prostaglandins do not seem to play a major role in the occurrence of brain edema due to prolonged regional ischemia. By contrast, oxygen-centered radicals released from the cyclooxygenase pathway appear to be at least partially responsible for the occurrence of recirculation-induced edema and postischemic hypoperfusion.
Stroke 1989 Jun
PMID:Effect of indomethacin and a free radical scavenger on cerebral blood flow and edema after cerebral artery occlusion in cats. 272 47

Pial arterioles of mice were suffused in situ with tert-butyl hydroperoxide (TBHP). This agent has been reported to stimulate synthesis or release of the constrictor, thromboxane. In the present study we observed pial arterioles by in vivo microscopy. Locally applied TBHP produced dose-dependent constriction, significantly inhibited by each of three drugs: acetylsalicylic acid, OKY-046, and SQ-29548. These drugs are respectively a cyclooxygenase inhibitor, a thromboxane synthetase inhibitor, and a thromboxane receptor blocker. Since each acts by a different mechanism to interfere with thromboxane-mediated responses and each inhibited the contractile response to TBHP, thromboxane appears to be a mediator of this response. Platelet aggregation was not seen after local application of TBHP, and the dwell time of platelets at the site of TBHP application is less than 1 second. Thus, platelets are an unlikely source of the thromboxane mediating the local constriction. It is much more likely that the source of thromboxane is either the wall of the pial vessels or the underlying brain and/or its vessels. These data do not distinguish between the latter two possibilities, but if this suggestion is correct, then the data show for the first time that thromboxane can be released from normal brain and/or brain vessels in amounts sufficient to cause arteriolar constriction.
Stroke
PMID:Evidence that in vivo constriction of cerebral arterioles by local application of tert-butyl hydroperoxide is mediated by release of endogenous thromboxane. 294 99

Vascular responses to acetylcholine (ACh) and the calcium ionophore A23187 were studied in rings of canine basilar arteries. In preparations that were precontracted to a stable plateau by 3 X 10(-6) M prostaglandin F2 alpha (PGF2 alpha), 10(-9) to 10(-7) M A23187 elicited significant relaxation of the basilar arteries if the endothelium was intact. Judging from histologic findings, the ability of a ring to relax in this manner is due to the presence of the endothelium. The same concentration of A23187 did not relax vascular tissues in which the endothelium was purposely disrupted. Although 10(-7) to 10(-3) M ACh did not sufficiently produce endothelium-dependent relaxation of canine basilar artery rings, ACh in the same concentration did produce significant relaxation in canine femoral rings. Our results suggest that the sensitivity of the muscarinic receptor of cerebral arteries appears to be appreciably different from that of peripheral (femoral) arteries. Pretreatment with 1.5 X 10(-5) M indomethacin, a cyclooxygenase inhibitor, potentiated the contractile responses produced by PGF2 alpha in intact rings. Preincubation with the lipoxygenase inhibitors nordihydroguaiaretic acid at (NDGA) at 1.5 X 10(-5) M or AA861 at 10(-5) M prevented A23187-induced relaxation. The same concentration of NDGA and AA861 did not affect endothelium-independent relaxation induced by glyceryl trinitrate. We suggest that endothelium-dependent relaxation of the canine basilar artery by A23187 may be mediated by noncyclooxygenase metabolite(s).
Stroke
PMID:Endothelium-dependent relaxation of canine basilar arteries. Part 1: Difference between acetylcholine- and A23187-induced relaxation and involvement of lipoxygenase metabolite(s). 311 18

The effects of the calcium ionophore A23187, arachidonic acid, and acetylcholine were studied in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in physiological saline. In unstimulated rings, A23187, arachidonic acid, and acetylcholine caused endothelium-dependent contractions. The contractions of rings caused by uridine 5'-triphosphate were not affected by removal of the endothelium. An inhibitor of cyclooxygenase, indomethacin (10(-5) M), prevented excitatory responses to A23187, arachidonic acid, and acetylcholine but did not alter contractions caused by KCl. An inhibitor of thromboxane synthetase, dazoxiben (10(-4) M), significantly reduced endothelium-dependent contractions to A23187 and arachidonic acid but did not significantly affect contractions caused by acetylcholine. These results demonstrate that A23187, arachidonic acid, and acetylcholine cause excitatory endothelium-dependent responses in canine cerebral blood vessels by increasing the release of product(s) of cyclooxygenase from endothelial cells; in the case of A23187 and arachidonic acid, thromboxane A2 contributes to the endothelium-dependent contractions.
Stroke 1988 Apr
PMID:Endothelium-dependent contractions to calcium ionophore A23187, arachidonic acid, and acetylcholine in canine basilar arteries. 312 26

It remains uncertain whether platelet activation in ischemic stroke is contributory or secondary to brain ischemia. The efficacy of aspirin (ASA) in stroke prevention suggests that platelet activation contributes to the occurrence of stroke. On the other hand, platelet activation may be simply a generalized consequence of cerebral ischemic damage. To examine this issue, plasma levels of the platelet specific proteins beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) were measured in fifty-eight patients with various defined types of acute ischemic strokes. beta-TG was a broader indicator of platelet activation than PF4. Compared with an age-matched control group, thromboembolic and cardioembolic stroke patients had significantly elevated beta-TG levels (p less than 0.001). Also, beta-TG levels in these stroke categories were significantly higher in samples drawn within the first week after the event than in those drawn later (p less than 0.001). In contrast, beta-TG levels in lacunar stroke patients and in most TIA patients were normal. beta-TG levels did not correlate with the volume of cerebral infarction as measured by planimetry from CT scans. Moreover, beta-TG levels in patients on chronic ASA therapy at the time of stroke did not differ from those in patients of the same diagnostic categories not taking aspirin. These data indicate that platelet activation may be important in some, but not all, subtypes of ischemic stroke and that platelet activation can occur in stroke even though the platelet cyclooxygenase pathway is suppressed.
Stroke
PMID:Enhanced in vivo platelet activation in subtypes of ischemic stroke. 316 Dec 20

The purpose of our experiment was to examine whether the cyclooxygenase inhibitor indomethacin ameliorates neuronal injury in the gerbil hippocampal CA1 sector following 5 minutes of forebrain ischemia. Thirty minutes before bilateral carotid artery occlusion, Mongolian gerbils were injected intraperitoneally with 1 (n = 10), 2 (n = 10), 5 (n = 12), or 10 (n = 7) mg/kg of indomethacin. Seven days after occlusion, the gerbils were perfusion-fixed and neuronal density in the hippocampal CA1 sector was assessed. The mean +/- SEM neuronal density in nine unoperated normal gerbils was 307 +/- 9/mm, in 10 untreated ischemic gerbils 55 +/- 21/mm, and in seven vehicle-treated ischemic gerbils 15 +/- 9/mm. The mean +/- SEM neuronal density in ischemic gerbils treated with 1, 2, 5, or 10 mg/kg indomethacin was 132 +/- 28/mm, 154 +/- 29/mm, 176 +/- 30/mm, and 136 +/- 39/mm, respectively. Indomethacin at any dose significantly ameliorated ischemic neuronal damage in the gerbil hippocampal CA1 sector.
Stroke 1988 Nov
PMID:Indomethacin ameliorates ischemic neuronal damage in the gerbil hippocampal CA1 sector. 318 24

The goal of this study was to determine whether responses of cerebral arterioles to products released by platelets are impaired in stroke-prone spontaneously hypertensive rats (SHRSP). The diameter of pial arterioles was measured during suffusion with adenosine 5'-diphosphate (ADP), serotonin, and the thromboxane analogue U-46619, using intravital microscopy in normotensive Wistar-Kyoto rats (WKY) and SHRSP (7-10 months old). Responses of cerebral arterioles to ADP and serotonin were profoundly impaired in SHRSP. ADP (10(-5) M) increased pial arteriolar diameter 17 +/- 3% (mean +/- SE) in WKY and only 4 +/- 1% in SHRSP. Serotonin (10(-5) M) increased pial arteriolar diameter 15 +/- 2% in WKY and, in contrast, reduced the diameter 13 +/- 1% in SHRSP. Nitroglycerin produced a similar dilatation of cerebral arterioles in WKY and SHRSP, suggesting that impairment of dilatation in SHRSP in response to ADP and serotonin was not related to nonspecific impairment of vasodilatation in SHRSP. The thromboxane analogue U-46619 produced a similar constriction of arterioles in WKY and SHRSP. We also examined the possibility that impaired dilator responses of cerebral arterioles in SHRSP in response to ADP and serotonin may be related to production of a cyclooxygenase vasoconstrictor substance. Indomethacin (10 mg/kg i.v.) partially restored dilator responses to ADP and serotonin in SHRSP, without altering responses in WKY. Thus, we speculate that vasoactive substances released by platelets may release a prostanoid constrictor substance from cerebral vessels of SHRSP and thereby predispose SHRSP to cerebral ischemia and, perhaps, stroke.
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PMID:Responses of cerebral arterioles to adenosine 5'-diphosphate, serotonin, and the thromboxane analogue U-46619 during chronic hypertension. 320 60

Two lines of evidence strongly support the hypothesis that high potassium diets protect arterial endothelial cells from hypertensive damage. Stroke-prone spontaneously hypertensive rats (SHRSP) fed normal (0.75%) K or high (2.1%) K and normotensive Wistar-Kyoto rats (WKY) were examined in an endothelial function study and a histological study. In the endothelial function study, aortic rings were suspended in tissue baths to monitor isometric tension. Rings contracted with norepinephrine were tested with acetylcholine and sodium nitroprusside. In normal K SHRSP (blood pressure, 156 mm Hg), endothelium-dependent acetylcholine relaxation was severely depressed by 49% (p less than 0.001), whereas in high K SHRSP (blood pressure, 155 mm Hg), normal values were preserved. Endothelium-independent nitroprusside relaxation was virtually the same in both the SHRSP groups (high K vs normal K diet). Since indomethacin did not improve the impaired acetylcholine relaxation in normal K SHRSP, the cyclooxygenase products do not appear to have affected the endothelium-dependent relaxation in the normal K SHRSP. Thus, the endothelium-dependent relaxation response was much decreased in the normal K SHRSP and was preserved in the high K SHRSP. Thus, a high K diet appears to protect the aortic endothelium from a hypertension-induced dysfunction. In the histological study, aortic and mesenteric intimal lesions were assessed blindly under the microscope and graded from 0 to 60 for aortic and from 0 to 40 for mesenteric lesions. Aortic intimal lesion scores were 28 in normal K SHRSP (blood pressure, 209 mm Hg) and 13 in high K SHRSP (blood pressure, 207 mm Hg; -54%; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High potassium diets protect against dysfunction of endothelial cells in stroke-prone spontaneously hypertensive rats. 326 May 81

Six anesthetized dogs treated with indomethacin, prostacyclin (PGI2), and heparin were compared with 7 anesthetized controls (ischemia without treatment) to determine whether cyclooxygenase inhibition would lead to enhanced granulocyte accumulation because of preferential formation of lipoxygenase products. Cortical somatosensory evoked response, [14C]iodoantipyrine autoradiographic blood flow, and 111In-labelled granulocyte accumulation were compared 4 hours after a 60-minute exposure to multifocal brain ischemia. Treatment with indomethacin, PGI2, and heparin eliminated neuron-disabling brain blood flows without altering early postischemic granulocyte accumulation. Granulocyte accumulation after 4 hours of reperfusion was not significantly different in control and treated dogs. The final amplitude of the cortical somatosensory evoked response in the treated group averaged 38.0 +/- 13.6% (mean +/- SEM) of the corresponding baseline value compared with 21.0 +/- 4.6% in the control group, but this difference was not significant.
Stroke
PMID:Indomethacin, prostacyclin, and heparin improve postischemic cerebral blood flow without affecting early postischemic granulocyte accumulation. 329 33

The effect of the cyclooxygenase inhibitors ibuprofen and meclofenamate were studied to assess the role of prostaglandin release in mediating the hemodynamic response to acute pulmonary microembolism in awake rabbits. In Group I (n = 10), a control group receiving only saline infusion, there was no change in pulmonary artery pressure, thermodilution cardiac output, or pulmonary vascular resistance. Group II (n = 12) received sequential intravenous doses of polyacrylamide microspheres averaging 34 mu in diameter, and demonstrated a progressive decrease in cardiac output and stroke volume and increases in pulmonary artery pressure and pulmonary vascular resistance. Pretreatment with either ibuprofen (Group III; n = 10) or meclofenamate (Group IV; n = 9) resulted in no change in resting hemodynamics and only minimally altered the effect of microembolism on pulmonary artery pressure. However, both ibuprofen and meclofenamate abolished the microembolism-induced decrease in cardiac output and stroke volume and blunted the increases in pulmonary artery pressure and pulmonary vascular resistance. The hemodynamic consequences of pulmonary microembolism in awake rabbits, particularly the decrease in cardiac output, are partly mediated by prostaglandin release, which alters pulmonary vascular tone and/or myocardial function.
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PMID:Prostaglandin mediation of hemodynamic responses to pulmonary microembolism in rabbits: effects of ibuprofen and meclofenamate. 358 84


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