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

Splanchnic artery occlusion (SAO) with subsequent reperfusion elicits a severe form of circulatory shock. To study the possible involvement of Ca2+ overload in this shock state, we have examined the effects of benidipine, a novel long-acting calcium antagonist, in a rat model of SAO shock, focusing on endothelial damage. Pentobarbital-anesthetized rats were subjected to 90-min occlusion of both the celiac and superior mesenteric arteries, followed by reperfusion. Rats given only the vehicle for benidipine developed hypotension following reperfusion, and only 7 of 16 rats (44%) survived 2 hr of reperfusion. In isolated superior mesenteric rings from SAO-shock rats, the EDRF-dependent dilator response to acetylcholine (ACh) (100 mM) was severely depressed (9% vs. 97% in control artery rings, P less than 0.001), whereas the EDRF-independent dilator response to acidified NaNO2 (100 microM) was unchanged. By contrast, 90% (9 of 10, P less than 0.05) rats treated with benidipine 45 min postocclusion (3 micrograms/kg, i.v.) survived 2 hr, and the dilator response to ACh was markedly improved (49% of initial, P less than 0.001). SAO-shock rats treated with benidipine also exhibited significantly attenuated accumulation of free amino-nitrogenous compounds (5.5 vs. 7.9 U/ml, P less than 0.05) and myocardial depressant factor (34 vs. 62 U/ml, P less than 0.001). These results suggest that endothelial damage plays a role in the pathogenesis of shock following bowel ischemia and reperfusion and that Ca(2+)-entry blockade improves endothelial function, which is involved in the amelioration of the shock state.
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PMID:Protection of endothelial damage and systemic shock by benidipine, a calcium antagonist, in rats subjected to splanchnic ischemia and reperfusion. 204 7

Pentobarbital pretreatment may be used to predict biochemical events involved in ischemic brain damage following bilateral carotid artery ligations in the gerbil, since it reduces the subsequent edema and mortality. The effects of this anesthetic on the ischemia-induced modifications of cerebral arachidonic acid metabolism were investigated, in order to correlate observed alterations with tissue damage. Cerebral lipids were radiolabeled in vivo with [3H]arachidonic acid prior to 10 min of cerebral ischemia and 0-120 min of perfusion. Ischemia stimulated a 97.3% increase in unesterified [3H]arachidonate, which was due to the loss of label from choline, inositol, and ethanolamine glycerophospholipids. Tissue reperfusion stimulated further reductions in [3H]choline and [3H]inositol glycerophospholipids, while ethanolamine glycerophospholipid and triglyceride labeling increased. Inositol glycerophospholipid, but not choline glycerophospholipid, labeling returned to control level by 60 min of reperfusion. Pentobarbital pretreatment reduced the accumulation of [3H]arachidonate by 56.2% during ischemia. It increased the recovery of [3H]ethanolamine glycerophospholipids during the ischemic period and [3H]choline glycerophospholipids during the first 5 min of reperfusion. These effects accounted for the reduction of unesterified [3H]arachidonate observed during ischemia and reperfusion.
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PMID:Arachidonic acid metabolism in gerbil cerebra: effects of ischemia and pentobarbital. 212 4

We investigated the neuroprotective effect of pentobarbital, a GABAA receptor-effector, on ischemic neuronal damage in the gerbils. The animals were allowed to survive for 7 days after 10-min ischemia induced by bilateral occlusion of the common carotid arteries. Morphological changes and abnormal calcium accumulation were evaluated in selectively vulnerable areas after ischemia. Pentobarbital (40 mg/kg, IP), administered 30 min prior to ischemia, significantly reduced neuronal cell loss in the neocortex, the striatum, and the hippocampal CA3 sector. However, pentobarbital failed to prevent the damage to the hippocampal CA1 sector and the thalamus. 45Ca autoradiographic study also revealed that a marked calcium accumulation was found in the selectively vulnerable regions after ischemia, which was consistent with the extent of histological neuronal damage. The abnormal calcium accumulation was reduced in the sites corresponding to most of the regions in which the protective effect of pentobarbital was found. The results suggest that ischemia-induced neuronal damage may be partly caused by an imbalance between excitatory and inhibitory input.
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PMID:Regional neuroprotective effects of pentobarbital on ischemia-induced brain damage. 228 72

The effects of a new calcium channel blocker, 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)-piperazine dihydrochloride (KB-2796), on delayed neuronal death (DND) in the hippocampus were examined in gerbils in comparison with those of pentobarbital and flunarizine. The neuronal density in the hippocampal CA1 subfield was counted on the seventh day of recirculation following 5 min of bilateral carotid occlusion, and protein biosynthesis in the brain was also determined at 1, 2, 4, 24, and 72 h following occlusion. The drugs were intraperitoneally administered after recirculation. KB-2796 (10 mg/kg) significantly prevented DND in the CA1 subfield. Pentobarbital (40 mg/kg), but not flunarizine (3 and 10 mg/kg), inhibited DND. Protein synthetic activity in the CA1 subfield was reduced by ischemia and the reduction was not restored even at 72 h after recirculation. KB-2796 did not ameliorate the reduction of protein synthesis in the CA1 subfield by 24 h after recirculation, but in one of three animals restoration of protein synthesis was observed at 72 h of recirculation. Pentobarbital also restored the reduced protein synthesis in two of three animals at 72 h. These results suggest that calcium influx into neurons participates in the pathogenesis of DND, and also that KB-2796 might prevent both morphological and functional cell damage in CA1 neurons induced by transient ischemia.
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PMID:Effects of a new calcium channel blocker, KB-2796, on protein synthesis of the CA1 pyramidal cell and delayed neuronal death following transient forebrain ischemia. 279 19

Ischaemic rat brains were examined for temporal changes in phospholipase C activity with phosphatidylinositol; the effects of pentobarbital on the activity also were investigated. Ischaemia was produced by decapitation. Pentobarbital (60 mg/kg) was administered i.p. for 15 min before decapitation. The removed heads were incubated at 37 degrees C for 1, 5, 15 or 30 min and then quickly frozen in liquid nitrogen. After isolation of subcellular fractions from the brains, phospholipase C activity was measured for cytosol and microsomes, using radioactive phosphatidylinositol as a substrate. The results demonstrated that brain phospholipase C predominantly localized in the cytosol was dependent on Ca2+ for full activity and had neutral pH optima. Although the enzyme activity did not increase during ischaemia, pentobarbital inhibited phospholipase C activity in the cytosol but not in the microsomes. These observations suggest that pentobarbital may exert a cerebral protective action due to, at least in part, the repression of phospholipase C followed by a reduction of phosphatidylinositol breakdown, preventing perturbation to the integrity of membranes, during ischaemia.
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PMID:Inhibitory effect of pentobarbital on phospholipase C activity in ischaemic rat brain. 289 Oct 63

A series of putative neuroprotective agents was tested to determine their efficacy in preventing the loss of the CA 1 neurons of the hippocampus at 4 days following 5 min of bilateral ischemia in the gerbil. Agents associated with the GABAergic system were determined to be the most effective, but only when given prior to the ischemic episode, suggesting that there was a gamma-aminobutyric acid (GABA)-related event during ischemia which triggers the delayed neuronal death of these cells. In this report, the unidirectional release of GABA and glutamate from gerbil hippocampal slices was determined under conditions mimicking anoxia and/or ischemia. Pentobarbital, the most effective of the GABAergic agents, had little or no effect on the time-dependent release of glutamate. In contrast, pentobarbital reduced in release of GABA in both anoxia and ischemia, but only after 25 to 30 min of incubation.
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PMID:A role for gamma-aminobutyric acid (GABA) in the evolution of delayed neuronal death following ischemia. 290 68

These studies addressed the question of the in vivo distribution of rat brain hexokinase (HK), and whether physiologically relevant changes in the glycolytic rate are accompanied by changes in the distribution of HK. Homogenates of fresh tissue showed only 11-15% of the overt (assayable without added detergent) HK to be soluble (found in high-speed centrifugation supernatant fractions) when homogenization was begun within 15-20 s of sacrifice. Freeze-blown rat brain tissue also was used, coupled with a new technique wherein it was homogenized as it thawed in a buffered sucrose solution containing 1 mM EDTA. In tissue sampled 15 min (anesthetized) or 60 min (waking) after ip Nembutal injection (40 mg/kg), 23% of the overt HK and 79% of the total lactate dehydrogenase were soluble. The average phosphocreatine content of these and similar homogenates had decreased only 23% from in vivo levels, while ATP had decreased by 65%, due to the combined effects of a high level of endogenous ATPase, chelation of Mg2+ by EDTA, and the greater stability of Mg-ATP2- relative to Mg-ADP1-. These data indicated that the tissue experienced, at most, the equivalent of 6 s of complete ischemia prior to the completion of homogenization. Synaptosomes derived from rat and chicken cerebra were incubated at 37 degrees C in a physiological salt solution containing 10 mM glucose. Addition of veratridine has been shown to stimulate glycolysis and oxidative phosphorylation two- to threefold (H. T. Kyriazi and R. E. Basford (1986) J. Neurochem., in press), but did not alter the HK distribution, as 21% was found in the supernatant fractions of both control and veratridine-stimulated synaptosomes treated with digitonin. These results indicate that in brain tissue, large net movements of HK on and off the outer mitochondrial membrane do not occur, and thus play no role in the regulation of glycolysis.
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PMID:An examination of the in vivo distribution of brain hexokinase between the cytosol and the outer mitochondrial membrane. 294 9

A pharmacological analysis was carried out to determine the possible role of aberrant calcium fluxes, vasoactive arachidonic acid metabolites, and microvascular lipid peroxidation in the development of posttraumatic spinal cord white matter ischemia. Pentobarbital-anesthetized cats were treated intravenously 30 minutes before a 500-gm-cm contusion injury to the lumbar spinal cord with one of the following test drugs: the Ca++ channel antagonists verapamil, diltiazem, or nifedipine; the cyclo-oxygenase inhibitors ibuprofen or meclofenamate; the thromboxane A2 (TXA2) synthetase inhibitor furegrelate sodium; or the stable epoprostenol (prostacyclin, or PGI2) analogue ciprostene calcium alone or in combination with furegrelate sodium. Another group of animals was pretreated for 5 days before spinal injury with a combination of the antioxidants vitamin E and selenium in high doses. The hydrogen clearance technique was used to make repeated measurements of spinal cord blood flow (SCBF) in the dorsolateral funiculus of the injured segment before and for 4 hours after injury. In 11 untreated uninjured cats, the mean preinjury SCBF was 12.7 +/- 1.5 ml/100 gm/min. Following contusion, there was a progressive decline in SCBF to 6.8 +/- 0.4 ml/100 gm/min, or 53.5% of the preinjury level at 4 hours. In comparison, the Ca++ antagonists diltiazem and nifedipine (but not verapamil) prevented a significant posttraumatic decrease in SCBF. Similarly, both cyclo-oxygenase inhibitors (ibuprofen and meclofenamate) maintained SCBF within normal limits (10 ml/100 gm/min or greater). However, neither TXA2 synthetase inhibition nor the stable PGI2 analogue alone had a significant effect in preventing ischemia, whereas a combination of the two agents did serve to support SCBF. The most impressive preservation of posttraumatic SCBF, however, was observed in the antioxidant-treated animals. Based upon these results, a hypothesis is presented concerning the pathogenesis of posttraumatic central nervous system ischemia which integrates an injury-induced rise in intracellular Ca++, the increased synthesis of vasoactive prostanoids (such as prostaglandin F2 alpha and TXA2), and progressive microvascular lipid peroxidation.
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PMID:A pharmacological analysis of the pathophysiological mechanisms of posttraumatic spinal cord ischemia. 308 21

The bilateral hemispheric ischemia in rats was induced by the occlusion of bilateral common carotid arteries after permanent electrocauterization of bilateral vertebral arteries at the level of the second cervical vertebra. In ischemic rats, (a) electroencephalograms became flat immediately after occlusion of carotid arteries, and (b) mortalities reached maximum levels at day 3 after recirculation. These results suggested that a constant level of cerebral ischemia was produced in this rat model. Pentobarbital markedly inhibited the mortality in these ischemic rats, whereas cyproheptadine did not.
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PMID:Effects of pentobarbital and cyproheptadine on brain ischemia induced by bilateral occlusions of carotid arteries and vertebral arteries of second cervical vertebra in rats. 322 32

We studied the effects of human superoxide dismutase (h-SOD) in splanchnic artery occlusion (SAO) shock. Pentobarbital anesthetized rats subjected to total occlusion of the superior mesenteric and the celiac arteries for 40 min developed a severe shock state usually resulting in a fatal outcome within 20 min after the release of the occlusion. h-SOD (10 mg/kg) was infused intravenously starting at reperfusion and lasting for 10 min. SAO shock rats treated with h-SOD maintained postreperfusion MABP at significantly higher values compared to rats receiving the vehicle (final MABP 84 +/- 6 vs 46 +/- 1 mm Hg, P less than 0.01, respectively). Treatment with h-SOD attenuated the plasma accumulation of free amino-nitrogen compounds (P less than 0.01 from vehicle) as well as the activity of the lysosomal protease cathepsin D (P less than 0.05 from vehicle). Furthermore, the plasma activity of a myocardial depressant factor was significantly lower in h-SOD-treated rats than in SAO rats receiving only the vehicle (27 +/- 1 vs 64 +/- 3 U/ml, P less than 0.01). SAO shock rats treated with h-SOD also exhibited a significantly higher survival rate than the SAO shock +/- vehicle group (88% vs 11%, P less than 0.01, respectively). These results support the role of oxygen-derived radicals in the pathophysiology of SAO shock, and indicate that h-SOD effectively ameliorates the deleterious effects of oxygen radicals in this severe model of ischemia and reperfusion.
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PMID:Anti-shock effects of human superoxide dismutase in splanchnic artery occlusion (SAO) shock. 339 43


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