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

A group of estrogen-primed, ovariectomized rats was adrenalectomized and tested for sexual receptivity following hypothalamic implantations of PGE2. The combination of PGE2 and adrenalectomy led to severe debilitation as manifested by greatly reduced open-field activity scores and inhibition of estrogen and progesterone induced sexual receptivity. Neither exogenous progesterone nor corticosterone was able to restore these behaviors to normal levels. A mechanism involving PGE2 and adrenalectomy-induced transient ischemia was discussed as a possible cause of the debilitation.
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PMID:Debilitating interaction of adrenalectomy and intrahypothalamic implants of prostaglandin E2 upon open-field activity levels and sexual receptivity in estrogen-primed ovariectomized rats. 23 10

This review provides a summary and assessment of research involving renal prostaglandins. Arachidonic acid released from phospholipids is converted by prostaglandin cyclo-oxygenase in the kidney to PGF2, PGF2alpha, PGD2, and, possibly, to PGI2 and thromboxane A2. Production of PGE2 and PGF2alpha is predominately but not exclusively in the medulla, whereas degradative enzymes are present in both cortex and medulla. Prostaglandins enter the tubular lumen by facilitated transport and are partially reabsorbed from the urine in the distal nephron. Urine prostaglandins probably reflect renal synthesis. PGE2 and endoperoxides stimulate and PGF2alpha and indomethacin inhibit renal renin synthesis. In response to ischemia, vasoconstriction, or angiotensin II the kidney increases prostaglandin synthesis to modulate renal vascular resistance. In conscious animals or man no role has been established for prostaglandins in the maintenance of basal renal blood flow or renal sodium excretion. PGE influences renal water excretion by inhibiting the action vasopressin. Despite conflicting data there is evidence that renal prostaglandins are involved either primarily or secondarily in many types of hypertension. Inhibitors of prostaglandin cyclooxygenase have been used with success in Bartter's syndrome. Conflicting results in many areas of investigation may be resolved by the use of more accurate and reliable assays, careful handling of samples, and the use of urine to further investigate renal prostaglandin synthesis.
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PMID:Prostaglandins and the kidney. 33 46

There are few data in the literature suggesting that endogenous prostaglandins (PGs) might be involved in the pathomechanism of seizures. Since the mechanism of seizures inducted by exposure to oxygen high pressure (OHP) is not fully elucidated, this study was designed to investigate the effect of exogenous PG s and of indomethacin (a Pg synthesis inhibitor) upon the development and consequences of seizures in rats exposed to OHP (5 ata). In the animals pretreated with PGE2 (1 ng/kg s.c.) pre-seizure time was shortened, lung weight : body weight index increased and symptoms of respiratory failure potentiated, as compared with the control group. Indomethacin (5 mg/kg i.p) prevented the development of seizures and of pulmonary consequences of OHP exposure. Biochemical examination of brains has shown that velocity of free radical oxidation of lipids (reactions manifested by the breakdown of phospholipid fatty acids, mainly unsaturated ones) enhanced by OHP exposure, is further potentiated in rats pretreated with PGE2. Electron microscopic study has shown the alterations similar to those seen in brain ischemia and/or hypoxia, and the magnitude of changes was related to the intensity of symptoms evoked by OHP. The results show that cerebral and pulmonary consequences of OHP exposure are potentiated by exogenous PGE2 and prevented by inhibition of endogenous PG synthesis. This suggests that PGs and/or their active metabolites might be involved in the mechanism of oxygen toxicity during exposure to hyperbaric oxygen.
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PMID:Effect of prostaglandin E2 and of indomethacin upon cerebral and pulmonary consequences of exposure to hyperbaric oxygen in rats. 45 47

The effect of meclofenamate and indomethacin on renal blood flow and renal vascular resistance was determined under basal experimental conditions and during renal ischemia in pentobarbital-anesthetized dogs. Renal blood flow was measured with an electromagnetic flowmeter and renal arterial pressure was recorded from a catheter in the renal artery. Intra-arterial infusion of indomethacin or meclofenamate in concentrations of 4 and 4 to 8 mu-g/ml, respectively, did not cause any significant change in renal blood flow or renal vascular resistance under basal conditions. During the period of ischemia (50% reduction in renal blood flow), 4 mu-g/ml of either prostaglandin synthetase inhibitor caused a marked increase in renal vascular resistance. Prostaglandin E in the renal venous blood was decreased at the time renal vascular resistance was increased by meclofenamate. The renal vasoconstrictor response to angiotensin II injected intravenously was potentiated by both inhibitors under basal as well as ischemic conditions, which also suggested that prostaglandin synthesis was inhibited. The angiotensin antagonist 1-sar-8-ala-angiotensin II was infused intra-arterially in concentrations of 20 and 40 mmu-g/ml during renal ischemia. Subsequent administration of meclofenamate increased renal vascular resistance only slightly. The results of these experiments indicated that renal prostaglandins have more influence on renal blood flow during renal ischemia than under basal conditions, and that the renin-angiotensin system may be involved in activating synthesis and release of prostaglandins during ischemia.
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PMID:Influence of the renin-angiotensin system on the effect of prostaglandin synthesis inhibitors in the renal vasculature. 80 74

Cardiac prostaglandin release was studied in closed-chest dogs during acute coronary occlusion. Aortic and coronary sinus blood was obtained before, and at intervals after, balloon occlusion of the left anterior descending artery in seven dogs. Samples were assayed for prostaglandins F, E, and A by randioimmunoassay. All dogs demonstrated prostaglandin F release, Mean +/- SE postocclusion aortic levels were 0.26 +/- 0.01 ng/ml; coronary sinus levels were 0.67 +/- 0.01 ng/ml (P less than 0.001). In six dogs, prostaglandin E also was released. Mean postocclusion aortic levels were 0.24 +/- 0.01 ng/ml; coronary sinus, 0.44 +/- 0.01 ng/ml (P less than 0.001). There was no release of prostaglandin A. To examine the site of prostaglandin release, simultaneous samples from the aorta, the coronary sinus, and the great cardiac vein were obtained before and after left circumflex artery occlusion in six additional studies. The great cardiac vein drained effluent from nonischemic myocardium, whereas the coronary sinus drainage included blood from both ischemic and nonischemic zones. All six dogs demonstrated prostaglandin F release from the ischemic region. Mean postocclusion aortic prostaglandin F was 0.32 +/- 0.01 ng/ml. Coronary sinus prostaglandin F was 1.69 +/- 0.03 ng/ml (P less than 0.001), whereas the great cardiac vein level remained at 0.34 +/- 0.01 ng/ml (P greater than 0.05). Prostaglandin E was released from both ischemic and nonischemic regions. Mean aortic prostaglandin E was 0.21 +/- 0.01 ng/ml; great cardiac vein, 0.55 +/- 0.02 ng/ml (P less than 0.001); and coronary sinus, 1.07 +/- 0.04 ng/ml (P less than 0.001). These results have led us to conclude that the different local availability of prostaglandins E and F may influence the cardiac response to ischemia.
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PMID:Regional cardiac prostaglandin release during myocardial ischemia in anesthetized dogs. 126 7

In this study, the effects of iloprost (ZK 36374) and NDGA on warm ischemia and reperfusion injury in rat liver were investigated. Rats were given isotonic saline (control group), iloprost 25 micrograms/kg i.v. (group II) just before warm ischemia or NDGA 10 micrograms/kg i.v. (group III) 5 min before reperfusion or the same drugs were given together (group IV). Serum SGOT, SGPT, and LDH values and tissue malondialdehyde (MDA), glutathione (GSH), prostaglandin (PG)E2, and leukotriene (LT)C4 levels were determined after ischemia-reperfusion injury. Histopathologic examination of the liver was carried out under the light microscope. The serum SGOT, SGPT and LDH levels improved significantly in groups II, III, and IV when compared with the control group (p < 0.05). There was a significant decrease (p < 0.05) in tissue MDA levels and significant increase (p < 0.05) in tissue GSH levels in group I, when compared with group IV and the control groups. The values did not differ significantly in group IV when compared to controls. The LTC4/PGE2 ratio was low and histologic findings were worse in group III. In conclusion, iloprost was found to be beneficial in preventing the ischemia-reperfusion injury in the rat livers. NDGA, either by direct toxic effect or by shifting the arachidonic acid metabolism to the cyclooxygenase route, was not found to be as effective. Iloprost and NDGA did not exert a synergist effect.
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PMID:The effect of iloprost and NDGA in ischemia reperfusion injury in rat liver. 128 66

Cardiac ischemia and reperfusion are associated with increased prostaglandin levels in the coronary venous effluent. This study implemented an in vivo-in vitro technique to investigate regional alterations in heart tissue PGE2 and PGF2 alpha de novo production. Canine endocardial and epicardial explants were incubated following 5 min regional ischemia, or 5 min ischemia with 10 min reperfusion, induced in vivo in two groups of animals (n = 10 and 6, respectively). Ischemia produced a significant upsurge in endocardial but not in epicardial prostaglandin synthesis as compared with the non-ischemic zone: 7.6 +/- 0.7 versus 4.5 +/- 0.5 pg/mg tissue per h in PGE2 (P < 0.001) and 8.8 +/- 1.2 versus 6.8 +/- 1.2 pg/mg per h PGF2 alpha (P < 0.01). Following reperfusion, PGE2 was higher in the apparently normal than in the affected endocardium (5.8 +/- 0.6 versus 4.4 +/- 0.5 pg/mg per h, P < 0.05). Opposite changes occurred in the reperfused epicardium: 8.2 + 0.9 versus 4.9 +/- 0.7 pg/mg per h PGE2 (P < 0.01) and 11.1 +/- 0.9 versus 6.0 +/- 0.6 pg/mg per h PGF2 alpha (P < 0.001), for the reperfused as compared to the "normal" region, respectively. Our findings imply that the left ventricular wall is not homogeneous in its eicosanoid response to ischemia and reperfusion. "In mirror" changes were found between endocardium end epicardium and between the injured and the apparently normal regions.
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PMID:Epicardial versus endocardial "in mirror" changes in prostaglandin synthesis after short periods of ischemia and reperfusion. 129 26

In the isolated working rat heart model, we studied metabolic and hemodynamic effects of 5- and 30-min global ischemia followed by reperfusion and assessed the potentially beneficial effect of captopril 80 micrograms/ml added throughout the experiment. Creatine kinase (CK) and catecholamines were measured in coronary effluent. De novo eicosanoids (prostaglandin E2) synthesis was assessed in endocardial explants. Hemodynamic alterations occurred after 30-min ischemia and were reflected most dramatically by a reduction in cardiac output (CO 72 +/- 10% of baseline values in captopril vs. 68 +/- 16% in controls) without significant differences as a result of treatment. Captopril shortened reperfusion ventricular fibrillation (VF) duration (6.9 +/- 1.2 vs. 13.6 +/- 8.7 min, p less than 0.05) but had no effect on VF incidence. No differences occurred in norepinephrine (NE) outflow, whereas total CK release was greater in controls. Five controls versus none of the treated hearts (p less than 0.05) released trace amounts of epinephrine during reperfusion. Increased de novo PGE2 synthesis was demonstrated after 5-min I (465 +/- 168 vs. 238 +/- 75 pg/100 mg tissue per hour, p less than 0.01). Captopril stimulated production of PGE2 in normoxic hearts (p less than 0.02), but the difference was no more apparent in ischemic hearts. We conclude that captopril produces some biochemical and electrophysiologic evidence of myocardial salvage, but these effects are not sufficient to induce hemodynamic improvement after global ischemia and reperfusion.
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PMID:Effects of captopril on metabolic and hemodynamic alterations in global ischemia and reperfusion in the isolated working rat heart. 137 8

Prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) are the metabolites of arachidonic acid (AA) that increase in forebrain following global ischemia and reperfusion. These mediators are highly potent vasoconstrictors of cerebral arteries leading to enhanced vascular permeability that induces the formation of vasogenic edema. In this study, after developing an experimental animal model simulating the concept of ischemic penumbra in the rat, the levels of PGE2 and LTC4 produced in the forebrain were measured and the effects of these mediators in short duration and prolonged reperfusion were investigated and then correlated with neuropathological findings. We found statistically significant reduction both in PGE2 and LTC4-like activities after just 10 min ischemia (p less than 0.05, p less than 0.05). PGE2-like activity significantly increased in the 4th and 60th min of reperfusion (p less than 0.05, p less than 0.05). In the 15th min of reperfusion, PGE2 was found to be significantly reduced (p less than 0.005) that may be due to the formation of free oxygen radicals by activation of PG hydroperoxidase reaction that inhibits PGE2 production in the cyclooxygenase pathway. LTs were not significantly increased in any reperfused group. Inhibition of the lipoxygenase pathway of AA metabolism may occur as a result of 15-HPETE (15-hydroperoxyeicosatetraenoic acid) production. Pathologically, edema and degeneration of brain tissue were seen beginning from the 4th min of reperfusion that reached a peak in the 60th min of reperfusion which is in accordance with biochemical changes in the damaged tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostaglandin E2 and leukotriene C4 levels following different reperfusion periods in rat brain correlated with morphological changes. 140 66

Defibrotide (D), a polydeoxyribonucleotide obtained from mammalian lungs, reduced the ischemic contracture due to low perfusion (0.2 ml/min) of the isovolumic left heart of the rabbit and abolished the irregularity of the rhythm of the heart, thereby restoring the cardiomechanical activity upon reperfusion (20 ml/min). D stimulated the release of PG-like material. Indomethacin infusion completely prevented both the antiischemic activity of D and its ability to increase the generation of prostaglandins in the rabbit heart. Measurement by atomic absorption spectroscopy of calcium content in ischemic heart tissue and its mitochondrial fraction indicated that the ischemic procedure significantly increased tissue calcium content in both. D, Prostacyclin (PGI2) and Nifedipine protected the heart from ischemic ventricular contracture and prevented accumulation of calcium in the heart. The effect of D on preventing Ca++ overload was completely abolished by indomethacin infusion. The results indicate that the beneficial effects of Defibrotide in experimental ischemia are primarily due to a release of Prostaglandin E2 (PGE2) and PGI2, which in turn may inhibit the detrimental effects of calcium overload in myocytes and mitochondria.
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PMID:Defibrotide has antiischemic activity in perfused rabbit hearts, preventing tissue Ca++ overloading. 160 39


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