Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We assessed the effect of 1,3-butanediol on cerebral energy metabolism and edema after inducing multifocal brain infarcts in 108 rats by the intracarotid injection of 50-microns carbonized microspheres. An ethanol dimer that induces systemic ketosis, 25 mmol/kg i.p. butanediol was injected every 3 hours to produce a sustained increase in the plasma level of beta-hydroxybutyrate. Treatment significantly attenuated ischemia-induced metabolic changes by increasing the concentrations of phosphocreatine, adenosine triphosphate, and glycogen and by reducing the concentrations of pyruvate and lactate. Lactate concentration 2, 6, and 12 hours after embolization decreased by 13%, 44%, and 46%, respectively. Brain water content increased from 78.63% in six unembolized rats to 80.93% in 12 saline-treated and 79.57% in seven butanediol-treated rats 12 hours after embolization. (p less than 0.05). The decrease in water content was associated with significant decreases in the concentrations of sodium and chloride. The antiedema effect of butanediol could not be explained by an osmotic mechanism since equimolar doses of urea or ethanol were ineffective. Our results support the hypothesis that the beneficial effect of butanediol is mediated through cerebral utilization of ketone bodies arising from butanediol metabolism, reducing the rate of glycolysis and the deleterious accumulation of lactic acid during ischemia.
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PMID:Beneficial effect of 1,3-butanediol on cerebral energy metabolism and edema following brain embolization in rats. 221 11

The precise effects ethanol (ETOH), acetaldehyde (ACT) and acetate (AC) exert on microscopic resistance and capacitance vessels in skeletal muscle is unknown. In-situ studies on the skeletal (cremaster) microvasculature of the rat, using high-resolution television microscopy, were undertaken. Acute administration (topical, intra-arterial or iv) of ethanol (0.001-10%) to young rats produced a concentration-related vasoconstriction of arterioles (18-45 microns) and muscular venules (25-50 microns), ranging from a 7 to 80% reduction in microvessel lumen sizes. Acute administration of either ACT or AC, however, produced concentration-related vasodilatation of these same microvessels. No known amine or opiate pharmacologic antagonist or cyclooxygenase inhibitor could attenuate or prevent ETOH, ACT and AC from eliciting their unique microvascular responses. These new, direct in-situ microcirculatory findings clearly demonstrate: 1) ETOH exerts constrictor, and not dilator, effects on skeletal muscle microscopic resistance and capacitance vessels; 2) both ACT and AC exert dilator, and not constrictor, effects on these muscle microvessels; and 3) the effects of alcohol can not be due to metabolism to ACT or AC. A progressive increase in ischemia of the skeletal muscle microscopic resistance and capacitance vessels, over a period of time (weeks to years), could result in the well-known syndrome of alcoholic myopathy.
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PMID:Comparative effects of ethanol, acetaldehyde and acetate on arterioles and venules in skeletal muscle: direct in situ studies on the microcirculation and their possible relationship to alcoholic myopathy. 224 21

We used a gerbil model of cerebral ischemia to study the effects of ion channel blockers on neuronal death resulting from enhanced glutamate release and calcium ion influx. The common carotid arteries of gerbils were occluded for 5 minutes and injected intraperitoneally immediately after ischemia with an alkylene iminopropylene derivative (glutamate blocker) or a piperazinyl ethanol derivative (calcium blocker) given at high or low doses. Two vehicle groups received saline or 0.2% methyl cellulose solution. Seven days later, the gerbils were perfusion-fixed and their brains were processed for histologic study. The number of neurons per millimeter (neuronal density) of the CA1 region was calculated, and the neuronal density in each group was statistically compared using the Mann-Whitney U test. Compared with a control group not subjected to carotid ligation, neurons of the two vehicle groups and the low-dose calcium blocker group were almost nonexistent in the CA1 region. Neuronal densities of the glutamate blocker group and the high-dose calcium blocker group were similar and were found to be within normal limits by statistical analysis. Our study shows that detrimental membrane phenomena and the incidence of delayed neuronal death may be counteracted by the systemic administration of these ion channel blockers after ischemic insult.
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PMID:Prevention of delayed neuronal death in gerbil hippocampus by ion channel blockers. 245 32

Nimodipine, a Ca2+ antagonist with cerebrovasodilatory and anti-ischemic effects, binds to rat, guinea pig, and human brain membranes with high affinity (less than 1 nM). Only at higher concentrations has nimodipine been reported to block the release of some neurotransmitters and hormones from neuronal tissue. Nimodipine has no consistent effect on brain oxygen consumption or cortical ATP or phosphocreatine levels, although the ischemia-induced fall of brain ATP levels in gerbils or the lowering of intracellular brain pH in rabbits with focal cerebral ischemia were antagonized by the drug. In rats and baboons with middle cerebral artery occlusion, nimodipine was found to reduce neurological deficits without an increase in intracranial pressure or brain edema. Electrophysiological studies with nimodipine suggested a direct neuronal action. In rabbit dorsal root ganglion cells, concentrations as low as 20 nM were reported to block inward Ca2+ currents. Recent studies have suggested that nimodipine may also improve memory in brain-damaged or old rats, restore sensorimotor function and abnormal walking patterns of old rats, and accelerate acquisition of associative learning in aging rabbits. Blockade of age-related changes in Ca2+ fluxes in rat hippocampal neurones by nimodipine in vitro pointed to neuronal plasma membrane as the site of nimodipine action. The therapeutic usefulness of nimodipine appears not to be limited to cerebral ischemia, but may include dementia, age-related degenerative diseases, epilepsy, and ethanol intoxication.
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PMID:Pharmacological basis for the use of nimodipine in central nervous system disorders. 256 39

The concept of cytoprotection has been applied to many tissues afforded protection by drugs or endogenous chemicals against organelle, cyto- or histopathologic damage. We review here the "organoprotection" by lidocaine in rats and dogs as appraised by in vitro, ex vivo, and in vivo experiments with the stomach and heart, and as revealed at organelle to organ functional levels. Gastric mucosal lesions induced by 80% ethanol with 100 mM HCl on the ex vivo rat stomach were significantly reduced by lidocaine (2.2-4.4 mg/kg bolus followed by 66-132 micrograms/kg/min i. v. infusion). In anesthetized dogs with gastric corporeal lesions induced by increased gastric intraluminal pressure (50 mm Hg, 2.5 hrs), lidocaine (2.2 mg/kg bolus plus 66 micrograms/kg/min infusion) significantly reduced lesion severity. In the isolated rat heart, reperfusion after a 60 min period of ischemia induced localized cardiac mitochondrial swelling and disruption in ventricular apices which was greatly reduced if hearts were pretreated (15 min perfusion with lidocaine). In intact rats subjected to hemorrhagic shock, lidocaine pretreatment also facilitated shock resuscitation and reduced ultrastructural damage. In these diverse experiments, lidocaine organoprotection was likely mediated in part through reduction of ischemia induced organelle membrane damage and through reduction of reperfusion-induced superoxide and other oxygen-derived free radical related damage.
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PMID:Gastric and cardiac organoprotection by lidocaine. 259 5

The influence of long-term (26 weeks) and long-term plus acute ethanol administration on the development of acute pancreatitis was studied in rats. While both these treatments alone did not induce pancreatitis in any rat, extrapancreatic fat necrosis and histologic lesions of the pancreas were found in the majority of animal 24 hours after additional establishing of a pancreatic juice edema by an obstruction/hypersecretion mechanism. Severity and frequency of findings were significantly increased by additional short-term ischemia (25 min) of the pancreas. In control rats without ethanol ingestion, the edema receded without any lesions, and after additional ischemia significantly fewer rats exhibited signs of acute pancreatitis when compared to the ethanol-treated groups. An experimental model of acute alcoholic pancreatitis is presented with ethanol ingestion, temporary ductal obstruction and stimulation of secretion being essential constituents, which may be of clinical relevance, too.
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PMID:Experimental acute pancreatitis in rats after chronic and chronic plus acute ethanol administration in combination with a pancreatic juice edema. 275 27

The effects of chronic ethanol ingestion on the rat kidney were studied. Rats were fed a liquid diet containing ethanol for 5 weeks to induce chronic alcoholism. Renal ischemia was introduced by clamping the renal artery and vein either for 10 or 20 min. The glomerular filtration rate (GFR) and the renal blood flow (RBF) were determined by using I125-iothalamate and I131-iodohippurate. In the absence of renal ischemia, there were no significant differences in the renal function between nonalcoholic rats (n = 5) and alcoholic rats (n = 5): 380 +/- 30 vs. 403 +/- 27 microliters/min/100 g body weight (BW) in GFR, and 3.1 +/- 0.1 vs. 3.1 +/- 0.2 ml/min/100 g BW in RBF. The recovery of GFR measured 2 h following 10-min renal ischemia in both groups was not significantly different; the values returned to 340 +/- 40 microliters/min/100 g BW (nonalcoholic rats) and 246 +/- 22 microliters/min/100 g BW (alcoholic rats), respectively. The changes of RBF following 10 min ischemia were also similar in both groups. However, the effects of alcoholism on the renal function became apparent when animals were subjected to more prolonged renal ischemia. In nonalcoholic rats (n = 5), GFR and RBF measured 2 h following 20 min renal ischemia were 245 +/- 51 microliters/min/100 g BW and 2.5 +/- 0.4 ml/min/100 g BW, whereas in alcoholic rats (n = 5) the GFR and RBF were significantly decreased to 93 +/- 15 microliters/min/100 g BW and 1.1 +/- 0.2 ml/min/100 g BW, respectively (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kidneys of chronic alcoholic rats are more vulnerable to ischemic insult. 281 70

Using isolated hemoglobin-free perfused rat livers we studied the effect of low oxygen supply on ethanol hepatotoxicity in two models. In the first model resembling low blood supply, perfusion rate was lowered from 60 to 10 ml/min after a 30 min-equilibration phase and kept low for 60 min. As a consequence, oxygen consumption fell from 1.76 +/- 0.15 mumol/min/g to 0.51 +/- 0.02 mumol/min/g. In the second model, total ischemia was accomplished by interruption of the perfusion for 30 min and was followed by reperfusion at a perfusion rate of 60 ml/min for a further 30 min. In this model, oxygen consumption returned immediately to normal values upon reperfusion. In both models, low oxygen supply had no toxic effects of its own on livers from fed rats. While ethanol (3 g/l) given under normoxic conditions led to a moderate hepatotoxicity, its application in both models of partial as well as total ischemia and reperfusion resulted in a marked liver damage as evidenced by a strong release of sorbitol dehydrogenase, glutamate-pyruvate-transaminase, lactate dehydrogenase and glutathione, as well as by an increase in hepatic calcium content. Inhibition of ethanol metabolism by 4-methylpyrazol prevented liver damage in both models indicating that metabolism of ethanol is a prerequisite for its toxicity to occur. Also, hepatotoxicity was inhibited partially by catalase and superoxide dismutase and nearly totally by deferrioxamine and allopurinol. Thus, reactive oxygen species which are produced during ethanol metabolism as well as under conditions of low oxygen supply are mediators of hepatic damage in both models employed.
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PMID:Enhancement of acute ethanol hepatotoxicity under conditions of low oxygen supply and ischemia/reperfusion. The role of oxygen radicals. 281 46

Platelet-activating factor is released from inflammatory cells. It activates neutrophils, releases secondary messengers, and mediates mucosal ulceration and ischemia in the rat. We assessed its possible role in the pathogenesis of ulcerative colitis. Colonic biopsy specimens from patients with active ulcerative colitis and controls were incubated for 4 h in Tyrode's buffer in the presence or absence of 0.2 microM calcium ionophore (A23187) or 50 microliter of antihuman immunoglobulin E. Platelet-activating factor was determined in the tissue by aggregation assay after extraction with 80% ethanol and was confirmed by thin-layer chromatography and its inactivation by phospholipases. Platelet-activating factor was not detected in normal mucosa. Only A23187 and antihuman immunoglobulin E stimulated its activity: mean +/- SE, 43.2 +/- 8.6 and 33.0 +/- 6.1 pg/10 mg wet wt, respectively. In active ulcerative colitis basal platelet-activating factor activity was 8.9 +/- 3.5 pg/10 mg wet wt. A23187 and antihuman immunoglobulin E induced significantly higher stimulation of platelet-activating factor synthesis when compared with their effects on normal mucosa: 200 +/- 28 and 70 +/- 8.3 pg/10 mg wet wt, respectively. The enhanced stimulation induced by A23187 was dose-dependently inhibited by salazopyrine, 5-amino-salicylic acid, and prednisolone, but not by sulfapyridine. It is thus suggested that platelet-activating factor may be involved in the pathogenesis of the inflammatory response in ulcerative colitis and that its inhibition by steroids, 5-aminosalicylic acid, and salazopyrine may be an additional mechanism to explain their therapeutic effects.
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PMID:Role of platelet-activating factor in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine and prednisolone. 290 95

Rabbits received ethanol p.o. (0.96 g. ml-1, 2.88 g.kg-1) for 30 days. Ischaemia was induced by abdominal aorta ligation for 40 min in animals with or without ethanol treatment. The content of total (TPL) and individual phospholipids, i.e. ethanolamine (PE), choline (PC), serine (PS), phospholipids and sphingomyelin (SM), as well as unesterified cholesterol (UC) was determined in the gracilis fascicle (Fg), and the dorsal (Dp) and ventral (Vp) part of the lumbar and cervical spinal cord. Chronic ethanol treatment resulted in a statistically significant decrease in the PE content in Dp of cervical spinal cord. Cholesterol content was increased in all parts of the spinal cord studied (increased UC/TPL molar ratio). Ischaemia of the spinal cord induced a significant decrease in PI. In ethanolic animals ischaemia decreased the PS content in Dp and Vp of ischaemized lumbar spinal cord. The combined effect of ischaemia and chronic ethanol did not result in a cumulative pattern of changes suggesting a partially opposite influence of both stimuli on lipid metabolism as well as its altered regulation after chronic ethanol treatment in the spinal cord.
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PMID:Effect of chronic ethanol treatment and subsequent ischaemia on phospholipids and cholesterol in the rabbit spinal cord. 297 17


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