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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secondary motor dysfunction is often observed following ischemic episodes in the central nervous system. To study potential mechanisms of postischemic motor deterioration, we developed a rabbit spinal cord ischemia model that has characteristics similar to the clinical condition termed deteriorating stroke. In this model, 70% of the rabbits regained substantial motor function by 4 hours after complete hindlimb paralysis during lumbar spinal cord ischemia; however, over the next 20 hours motor function steadily declined to the point where only 30% of the rabbits had minimal hopping function. The role of eicosanoids in spinal cord ischemia was studied by radioimmunoassay of several prostaglandins (6-keto-PGF1 alpha, PGE2, and TxB2) in the spinal cord. After 5 minutes of reperfusion, TxB2 levels were markedly elevated (p less than 0.05) while 6-keto-PGF1 alpha levels did not change. The TxB2:6-keto-PGF1 alpha ratio was also significantly increased. After 30 minutes of reperfusion, PGE2 levels were also elevated (p less than 0.05). Tissue edema measured by microgravimetry was also increased after 30 minutes of reperfusion in both gray and white matter. By 4 hours of reperfusion, rabbits regained near-normal hindlimb motor function while PGE2, 6-keto-PGF1 alpha, TxB2, and tissue water content were back to normal. However, by 18 hours of reperfusion, when hindlimb function was deteriorating, TxB2 levels were elevated again, and edema in gray and white matter was increased as was the number of necrotic neurons observed by light microscopy. These results suggest that the secondary deterioration of motor neurologic function was due to the excess formation of TxA2 primarily in the late reperfusion phase. However, further studies are necessary to elucidate the relation of TxA2 with ischemic neural injury.
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PMID:Deteriorating stroke model: histopathology, edema, and eicosanoid changes following spinal cord ischemia in rabbits. 360 1

Ischemia of abdominal visceral organs is known to reflexly stimulate the cardiovascular system. The purpose of this study was to determine which of several potential chemical stimuli present during ischemia either directly stimulate or sensitize these afferents to respond to ischemia. Impulse activity was recorded in the right splanchnic nerve of anesthetized cats. First, we determined whether the afferents were ischemically sensitive by subjecting them to 2-6 min of regional ischemia through occlusion of the descending thoracic aorta. We then examined the afferents' response to systemic hypoxia by decreasing the inspired O2 and arterial injection of bradykinin or the prostaglandins (PG) E2, PGF2 alpha, or prostacyclin (PGI2). Sixty-one percent of the rapidly adapting A fibers and 47% of the C fibers were stimulated by ischemia, and of these, 78% of the A fibers and 44% of the C fibers tested were stimulated by hypoxia. The latency of response to hypoxia (60 +/- 12 s) was significantly longer than the chemoreceptor-induced pressor response (45 +/- 11 s). Each afferent stimulated by ischemia and/or hypoxia innervated a receptive field in the pylorus, intestine, porta hepatis, gallbladder or biliary tract, pancreas, or mesentery. Ninety percent of the ischemically sensitive A fibers and 80% of the ischemically sensitive C fibers responded to bradykinin, whereas 40% of the A fibers and 62% of the C fibers responded to PGE2, PGF2 alpha, or PGI2. Several endings responded to ischemia or hypoxia only after bradykinin or PGI2 had been injected. Thus approximately 50% of slowly adapting A and C fiber endings in abdominal visceral organs respond, or can be sensitized by bradykinin or PGI2 to respond, to ischemia and/or hypoxia. However, they are not as sensitive to hypoxia as carotid and aortic body chemoreceptors, since they respond well after the chemoreceptor-induced pressor response.
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PMID:Hypoxia, bradykinin, and prostaglandins stimulate ischemically sensitive visceral afferents. 363 Dec 93

This study examines the pathophysiology of stroke secondary to focal cerebral ischemia. The interaction of arachidonic acid metabolites and polyamines, a class of ubiquitous ornithine-derived molecules with important membrane effects on edema, Ca++-dependent endocytosis, platelet function, and prostaglandin (PG) formation, are correlated with regional changes in H2 clearance, cerebral blood flow (rCBF), ischemic edema, and somatosensory evoked responses (SSERs) after middle cerebral artery (MCA) occlusion. Thirty cats were studied up to 3 hours before and 6 hours after right MCA occlusion. Four areas of brain showing different levels of perfusion after MCA occlusion were sampled for tissue levels of PGs: 6-keto-PGF1 alpha, PGE2, and as well as thromboxane B2 (TXB2), ornithine decarboxylase activity (ODC) (a measure of polyamine activity) and gravimetric determination of cerebral edema. After right MCA occlusion, right hemisphere SSER amplitude decreased and interpeak latency increased markedly. rCBF was distributed into zones of dense, partial, and no ischemia ranging from 12.6 to 59.4 ml/100 g/minute. Ischemic edema was distributed inversely to rCBF and was increased in areas of dense ischemia (85.2 +/- 0.5%) and ischemia (82.7 +/- 0.7%), but not in partially ischemic or control areas. 6-Keto-PGF1 alpha (1257.3 pg/mg), PGE2 (1628.5 pg/mg), and TXB2 (1572.8 pg/mg) were all significantly (P less than 0.05) increased in areas of partial ischemia that had not yet developed edema. ODC levels were significantly elevated (3812 pmole/g/hour, P less than 0.05) and increased with time in areas of slightly denser ischemia that showed an intermediate increase in edema, but not the presence of infarction. This is the first demonstration that ODC, the rate-limiting enzyme for polyamine synthesis, is stimulated by cerebral ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Polyamine and prostaglandin markers in focal cerebral ischemia. 386 30

In a rat skin flap model, surgical delay produced an increase in the production of arachidonic acid metabolites, with a derangement of the normal equilibrium between PGE2 and PGF2 alpha and a marked increase in the vasoconstrictive substance, thromboxane. During the delay period, there is a gradual decrease in tissue levels toward normal. Subsequent elevation of the delayed flap produces a blunted response in thromboxane production, an increase in PGE2 levels and increased flap survival. Acute elevation of an undelayed flap produced more marked elevation of all metabolites, with prolonged elevation of the vasoconstrictive PGF2 alpha and thromboxane, progressive ischemia and decreased flap survival. A key role in inflammation, mediated by these inflammatory mediators, is postulated in the mechanism of delay.
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PMID:Surgical delay and arachidonic acid metabolites: evidence for an inflammatory mechanism: an experimental study in rats. 392 Oct 87

Using the rat middle cerebral artery occlusion model, alterations in the eicosanoid synthetic capacity of brain microvessels following ischemia were studied by radiochromatography. Brain microvessels of normal rats predominantly produced hydroxyacids with relatively small amounts of PGD2 and PGE2 from exogenous arachidonic acid. Confirmation that hydroxyacids and prostaglandins were products respectively of lipoxygenase(s) and cyclooxygenase was obtained by experiments using indomethacin and eicosatetraynoic acid. The eicosanoid synthetic capacity of the brain microvessel, especially of hydroxyacids, was significantly enhanced 24 and 72 hours after the onset of ischemia. Because this is the phase of maximum edema in the present model, enhanced eicosanoid production in the brain microvessel may be involved in the mechanisms that underly ischemic brain edema.
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PMID:Ischemic brain edema following occlusion of the middle cerebral artery in the rat. II: Alteration of the eicosanoid synthesis profile of brain microvessels. 396 53

Eicosapentaenoic acid prevents platelet aggregation and inhibits arachidonate conversion into thromboxane A2 and prostaglandins. Consequently eicosapentaenoic acid might protect the brain from the ischemia that follows cerebral arterial occlusion. We studied the effect of eicosapentaenoic acid on cerebral ischemia in anesthetized gerbils. Ischemia was produced by bilateral carotid occlusion for 10 min, followed by reperfusion for 60 min, in gerbils fed either a standard diet (control) or a diet supplemented with menhaden fish oil for 2 months. The menhaden fish oil contained 17 mole % eicosapentaenoic acid. Regional cerebral blood flow was measured by the hydrogen clearance method and brain water by the specific gravity technique. In control animals cerebral blood flow was decreased 30 and 60 min after reperfusion (p less than .001) and brain water was increased (p less than .001). In the experimental group cerebral blood flow did not fall during reperfusion and edema did not appear. Brain prostaglandins and thromboxane were measured by radioimmunoassay. PGF2 alpha, PGE2, 6-keto PGF1 alpha and TXB2 increased after severe ischemia and reperfusion. The synthesis of brain diene prostaglandins was not altered by eicosapentaenoic acid. Our study indicates that eicosapentaenoic acid prevented post-ischemic cerebral edema and hypoperfusion, without affecting the levels of brain diene prostaglandin and thromboxane.
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PMID:Eicosapentaenoic acid: effect on brain prostaglandins, cerebral blood flow and edema in ischemic gerbils. 632 May 4

Prostaglandins in concentrations too low to stimulate afferent nerve endings in the heart may sensitize them to chemical or mechanical stimuli that activate cardiac reflexes during myocardial ischemia. Bradykinin, which is released from the heart during ischemia, elicits sympathetically mediated reflex pressor effects and tachycardia when applied in low doses (0.1 to 1 microgram) to the epicardium of the left ventricle in open-chest, anesthetized dogs. The reflex pressor effects evoked by bradykinin are reduced after inhibition of prostaglandins biosynthesis with indomethacin and potentiated by concomitant topical application of low doses (0.1 to 0.3 microgram/min) of PGE1 or PGE2 and prostacyclin (PGI2). The pressor and tachycardic responses to bradykinin are also enhanced after temporary (10-minute) coronary occlusion; this potentiation is abolished by indomethacin treatment and can be restored by superfusing the ventricle with prostaglandins. Nicotine is known to excite mechanosensitive vagal receptors with afferent C fibers, which supply the left ventricle, and to elicit reflex hypotension and bradycardia. This depressor vagal reflex evoked by epicardial or intracoronary administration of nicotine (10 to 50 micrograms) was not affected by either indomethacin or by topical application of PGE1, PGE2, or PGI2. Also, intracoronary infusion of PGE2 (0.1 to 0.3 microgram/min), which enhanced the pressor reflex effects of bradykinin, was without effect on nicotine-induced depressor reflex. However, intracoronary infusion of PGI2 (0.1 to 0.3 microgram/min) significantly enhanced the hypotensive and bradycardic responses to nicotine and, at the same time, reduced sympathetically mediated reflex effects of bradykinin. The hypotensive effects induced by epicardial or intracoronary administration of nicotine were also significantly enhanced during intravenous infusion of subdepressor doses of PGI2 (5 to 20 ng/kg/min). Treatment with captopril, which enhances the endogenous production of prostaglandins, greatly enhanced the reflex depressor effects of nicotine; this potentiating effect of captopril was completely abolished by indomethacin treatment. An increase in the magnitude of nicotine-induced reflex depressor effects was also observed after intravenous injection (1 microgram/kg) or infusion (25 to 50 ng/kg/min) of prostaglandin D2. A working hypothesis is proposed to account for the role of prostanoids in activation of cardiac reflexes during myocardial ischemia.
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PMID:Prostanoids and cardiac reflexes of sympathetic and vagal origin. 634 52

Rat brain slices released spontaneously and after challenge with A23187 LTC4-like radioimmunoactivity. Total cat brain ischemia followed by short postischemic reperfusion period resulted in the increased release of lipid peroxides and PGE2 but not in LTC4-like substance by brain slices. In lumbar cerebrospinal fluid of patients with completed stroke presence of LTC4-like material was observed.
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PMID:Formation of lipoxygenase and cyclooxygenase metabolites of arachidonic acid by brain tissue. 644 May 38

Renal cortical prostaglandin synthesis, particularly by arterioles and glomeruli, is important to preserve renal blood flow (RBF) and glomerular filtration rate (GFR). Glomeruli and arterioles synthesize not only the vasodilatory prostaglandins PGE2 and PGI2, but also the vasoconstrictor, thromboxane A2. The primary renal cortical actions of these prostaglandins are renal vasodilatation and maintenance of GFR (PGE2 and PGI2) or renal vasoconstriction and reduction of GFR (thromboxane A2). Vasodilatory renal prostaglandins are relatively unimportant under normal circumstances but play a modulatory role after ischemia or in the presence of increased concentrations of vasoconstrictor substances such as angiotensin II (ANG II), vasopressin or norepinephrine. ANG II and vasopressin stimulate the synthesis of PGE2 in rat glomerular epithelial and mesangial cells maintained in cell culture. These stimulatory actions of constrictor peptides are dependent upon calcium entry into the cells since removal of extracellular calcium or co-incubation with verapamil or nifedipine block the prostaglandin stimulatory capacity of ANG II or vasopressin. In vivo indomethacin potentiates the actions of ANG II on the kidney, particularly the reduction of RBF and GFR. Isolated rat glomeruli contract in response to ANG II and this contractile effect, which reflects reduction in glomerular filtration surface area, can be potentiated by cyclooxygenase blockade. Conversely, arachidonic acid reduces the glomerular contractile effect of ANG II. The importance of renal prostaglandins in support of RBF and GFR has been studied in dogs after chronic bile duct ligation (CBDL). CBDL dogs have significant increase in renal PGE2 and PGI2 which maintain RBF and GFR since cyclo-oxygenase inhibition resulted in a 50% decrease in both RBF and GFR. Indomethacin, ibuprofen, naproxen, and sulindac sulfide had comparable effects. The pro-drug, sulindac sulfoxide, was tested in normal volunteers and found to spare renal prostaglandin synthesis whereas indomethacin reduced renal synthesis of PGE2 and PGF2 alpha by more than 50%. In vitro, sulindac sulfide is a potent inhibitor of renal prostaglandin synthesis by kidney cells in culture. It is, therefore, concluded that renal prostaglandins play an important vasoregulatory role. Furthermore, sulindac sulfoxide may spare renal cyclo-oxygenase and thereby preserve renal function.
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PMID:Mechanisms of the nephrotoxicity of non-steroidal anti-inflammatory drugs. 659 99

Several of the cyclooxygenase products of arachidonic acid were measured in the cerebral hemispheres of gerbils subjected to transient interruption of the cerebral circulation. The levels of PGD2, PGF2 alpha, PGE2, TXB2, 13, 14-H2-15-keto-PGE2, and the stable nonenzymic product of prostacyclin, 6-keto-PGF1 alpha, were not altered at the end of a 5-min period of ischemia. However, the onset of reperfusion was accompanied by a rapid accumulation of these products. Levels were highest during the initial period of reperfusion, then decreased to approach control levels after 120 min. PGD2, PGF2 alpha, and PGE2 were the predominant metabolites detected. This postischemic accumulation of arachidonic acid metabolites could be blocked by prior administration of inhibitors of cyclooxygenase activity.
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PMID:Accumulation of cyclooxygenase products of arachidonic acid metabolism in gerbil brain during reperfusion after bilateral common carotid artery occlusion. 677 64


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