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

With the purpose to define the specific activity of substances acting on the cerebral circulation and metabolism, (-)eburnamonine and cinnarizine were compared in a double-blind study carried out in a group of 106 elderly patients suffering from established chronic brain ischemia. The photoscintigraphic and rheoencephalographic studies carried out on some of the patients showed that only (-)eburnamonine had a clear-cut activity on brain circulation. (-)Eburnamonine also showed an activity on kidney circulation. With regard to the clinical picture, a statistical evaluation of the results obtained showed that both drugs improve psychic disturbances and the overall clinical picture. Cinnarizine appears to influence, to a slightly greater extent, some neurological symptoms, while (-)eburnamonine exerts a significantly better action on daily living activities and general psychic efficiency.
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PMID:Therapy of chronic consequences of brain ischemia. Comparison between two drugs acting on brain circulation and metabolism. 38 Oct 5

Male and female, arteriosclerotic and non-arteriosclerotic rats were treated with the anti-lipemic agent, clofibrate, for 8 days and then subjected to an acute myocardial infarction by injecting them with two large doses of isoproterenol spaced 24 hours apart. The animals were killed at sequential time intervals during the acute necrosis and early repair phases of myocardial infarction. Pre-treatment with clofibrate caused a definite improvement in survival, less shock and prostration, and ECG evidence of little or no ischemia. Increased SGOT levels, hepatic lipid and necrosis were indicative of advanced liver damage. Although clofibrate-treated animals showed little change in serum lipids during the acute cardiac necrosis phase, they were hyperglycemic and showed the greatest increase in BUN levels. Clofibrate-treated animals had higher serum corticosterone levels than those given isoproterenol alone. Despite superior survival rates, both the arteriosclerotic and non-arteriosclerotic, clofibrate-treated animals exhibited equally severe histopathologic evidence of myocardial damage. It is suggested that the protective effect of prophylactic treatment with clofibrate against isoproterenol-induced myocardial infarction in rats may be due to its ability to change corticosterone levels in the circulation.
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PMID:Protective effects of clofibrate on isoproterenol-induced myocardial infarction in arteriosclerotic and non-arteriosclerotic rats. 66 86

The central effects of endothelin-1 (ET-1) and their modification by the calcium entry blocker cinnarizine have been investigated using CNS and hypoxia/ischemia tests. CNS tests comprised behavior, horizontal and vertical motor activity and hot plate test. Hypoxia/ischemia tests used were hypobaric hypoxia and complete ischemia by decapitation. ET-1 was injected intracerebroventricularly (i.c.v.) in a volume of 0.01 ml at doses of 1.25, 2.5 and 5 pmol/mouse 15 min before the tests. Cinnarizine (10 mg/kg, i.p.) was administered 60 min prior to ET-1. The i.c.v. ET-1 at all the doses used decreased horizontal and vertical motor activity and produced barrel-rolling. Survival/gasping time of mice subjected to hypoxia/ischemia increased dose-dependently. ET-1 showed an antinociceptive effect. Cinnarizine attenuated the appearance of barrel-rolling, did not antagonize disturbances in motor activity and reversed the antinociceptive effect of ET-1. In hypobaric hypoxia and decapitation cinnarizine antagonized the effects of 5 pmol/mouse ET-1 and potentiated that of 1.25 pmol/mouse. The pharmacological modification of the ET-1 effects by cinnarizine strongly suggests that the CNS actions of ET-1 might be due to multiple mechanisms triggered by an increased influx of extracellular Ca2+ into the brain cells.
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PMID:Effects of intracerebroventricular endothelin-1 on CNS and cerebral hypoxia/ischemia and their modification by cinnarizine. 149 99

Temporary cerebral ischemia (15 min) produced by "four-vessel occlusion" in the rat causes neurological disorders, changes in behavior (locomotor hyperactivity), and neuronal damage in the neocortex, striatum, and especially the CA1 zone of the hippocampus. We have studied the effects of two calcium overload blockers, flunarizine (50 mg/kg p.o. twice a day) and cinnarizine (100 mg/kg p.o. twice a day), on these alterations. Cinnarizine markedly improved the functional abnormalities of ischemia but had little or no effect upon the neuronal damage. In contrast, flunarizine provided far greater neuronal protection but with less obvious effects upon behavioral parameters. However, there was evidence of sedation 2 h after treating animals with this dose of flunarizine that might have masked any positive effect of the drug on behavior. We conclude that under the present experimental conditions, there is no correlation between the early and late behavioral changes observed following a temporary cerebral ischemic episode and the histological damage observed in certain vulnerable neurons, particularly in the hippocampus, 72 h after the insult.
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PMID:Functional, behavioral, and histological changes induced by transient global cerebral ischemia in rats: effects of cinnarizine and flunarizine. 277 34

The increase of cellular fatty acids appears to be one of the causes of the myocardial injury during ischemia and reperfusion. This study was designed to examine whether a hypolipidemic drug such as clofibrate can reduce the myocardial injury during ischemia and reperfusion. Clofibrate was fed to experimental pigs for 9 days. Isolated in situ hearts from both experimental and control pigs were subjected to 60 min of regional ischemia induced by occluding the left anterior descending coronary artery, followed by 60 min of global ischemia by hypothermic cardioplegic arrest and 60 min of reperfusion. The clofibrate feeding resulted in the better cardiac performance as judged by increased coronary blood flow, improved left ventricular function, and reduced myocardial injury as judged by creatine kinase release. Although the clofibrate-fed animals contained higher levels of thiobarbituric reactive materials, the free fatty acid levels of plasma and myocardium were much lower compared with control animals. The clofibrate feeding was also associated with increased peroxisomal catalase and beta-oxidation of fatty acids. These results suggest that decreased levels of free fatty acids in the plasma and the myocardium and increased catalase activity induced by antilipolytic therapy appear to provide beneficial effects to the myocardium during ischemia and reperfusion.
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PMID:Improved myocardial performance induced by clofibrate during reperfusion after acute myocardial infarction. 322 87

The anti-hypoxic effect of cinnarizine was studied using the following experimental methods: hypobaric and anoxic hypoxia in mice, complete ischemia by decapitation in mice and hemic hypoxia in rats. Papaverine, xanthinol nicotinate and naftidrofuryl were used as reference drugs. In hypobaric and anoxic hypoxia the interaction of cinnarizine with the effect of prostacyclin (PGI2) was investigated. Cinnarizine showed an anti-hypoxic effect in all the methods used. It was more effective in hypobaric and anoxic hypoxia, in incomplete ischemia by decapitation, and less effective in hemic hypoxia. Cinnarizine potentiated the effect of PGI2 shifting the anti-hypoxic dose-response curve of PGI2 to the left. Suggestions as to the possible mechanism of anti-hypoxic action of cinnarizine are made.
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PMID:Study on the anti-hypoxic effect of cinnarizine and its interaction with prostacyclin. 637 43

The anti-hypoxic effect of piracetam was studied using the following experimental methods: hypobaric and anoxic hypoxia in mice, complete ischemia by decapitation in mice, incomplete ischemia by bilateral carotid occlusion in rats and hemic hypoxia in rats. Cinnarizine and vinpocetine were used as reference drugs. In hypobaric hypoxia, anoxic hypoxia, and complete ischemia by decapitation the interaction of piracetam with the effect of prostacyclin (PGI2) was investigated. Piracetam showed anti-hypoxic effect in all the methods used. Its effect was greater than that of cinnarizine and similar to that of vinpocetine. Piracetam potentiated the effect of PGI2 shifting the anti-hypoxic dose-response curve of PGI2 to the left.
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PMID:Anti-hypoxic effect of piracetam and its interaction with prostacyclin. 639 21

This study tested the hypothesis that cytochrome P450 (P450) metabolites of arachidonic acid (AA) contribute to the vascular changes in ischemia/reperfusion (I/R) injury in the rat. In this study, P450-dependent omega-hydroxylase-mediated vascular reactivity of the rat renal interlobular and arcuate vessels [preglomerular vessels (PGMV)] was measured in left kidneys subjected to I/R. Clipping the left renal artery and vein for 30 min followed by reperfusion (I/R) for 3, 6, and 24 h markedly reduced renal microsomal omega-hydroxylase-mediated conversion of [(14)C]AA to 20-hydroxyeicosatetraenoic acid (HETE) that amounted to 34, 37, and 58% of the control enzyme activity, respectively. CYP4A protein expression was also reduced. There was no significant change in epoxygenase activity. Despite these changes, constriction of the rat PGMV by AA or endothelin-1 (ET-1) was not different in vessels from the clipped and nonclipped (contralateral) kidney. Clofibrate (250 mg/kg i.p.), an inducer of CYP4A protein and omega-hydroxylase enzymes, did not increase 20-HETE production but selectively enhanced the vasoconstriction produced by AA and ET-1 in the clipped but not the contralateral kidney without affecting the constriction produced by 9,11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F(2alpha). On the other hand, administration of 2% NaCl (w/v, orally for 7 days) to induce P450-dependent epoxygenase activity attenuated AA-induced vasoconstriction but enhanced ET-1-induced vasoconstriction only in the clipped kidney. These data indicate that the reduction in CYP4A protein expression and enzyme activity in I/R is an adaptive mechanism to preserve renal vasculature from excessive vasoconstriction. Moreover, the increase in epoxygenase activity following salt loading may account for the diminished vasoconstriction evoked by AA. However, the enhancing effect of salt on ET-1-induced vasoconstriction in I/R appears to result from an overwhelming effect of salt-induced sensitization of the renal vasculature to ET-1 over the enhanced production of dilator epoxygenase products.
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PMID:Renal cytochrome p450 oxygenases and preglomerular vascular response to arachidonic acid and endothelin-1 following ischemia/reperfusion. 1213 Jul 36

Prevention of myocardial injury has been considered as the most important therapeutic challenge of today. Fibrates, the agonists of the peroxisome proliferator-activated receptor (PPAR)-a receptor, have been regarded as potent therapeutic agents in this context. Hence, the present study has been designed to investigate the effect of fibrates, i.e., Clofibrate and Fenofibrate, the potent agonists PPAR-a, on ischemia-reperfusion (I/R)-induced myocardial injury. The isolated Langendorff-perfused rat hearts were subjected to global ischemia for 30 minutes followed by reperfusion for 120 minutes. Myocardial infarct size and the release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary effluent have been conducted to assess the degree of cardiac injury. Moreover, the oxidative stress in the heart was assessed by measuring lipid peroxidation, superoxide anion generation, and reduced glutathione. Clofibrate and Fenofibrate showed cardioprotection against I/R-induced myocardial injury in rat hearts as assessed in terms of reductions in myocardial infarct size, LDH, and CK levels in coronary effluent along with reduction in I/R-induced oxidative stress. It may be concluded that the observed cardioprotective potential of Clofibrate and Fenofibrate against I/R-induced myocardial injury was due to the reductions in infarct size and oxidative stress.
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PMID:Protective role of fibrates in cardiac ischemia/reperfusion. 2305 6