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

Recent experimental data indicate a probable role of adenosine as an endogenous neuroprotective substance in brain ischemia. This nucleoside is rapidly formed during ischemia as a result of intracellular breakdown of ATP and it is subsequently transported into the extracellular space. With use of microdialysis and other techniques, a massive increase of interstitial adenosine has been measured during ischemia in different brain areas. Adenosine acts through two subtypes of receptors, A1 and A2, which are located on neurons, glial cells, blood vessels, platelets, and leukocytes and are linked via G-proteins to different effector systems such as adenylate cyclase and membrane ion channels. There is a very high density of A1-receptors in the hippocampus, an area with specific vulnerability to ischemia. In different in vivo and in vitro models of brain ischemia, the pharmacological manipulation of the adenosine system by adenosine receptor antagonists tended to aggravate ischemic brain damage, whereas the reinforcement of adenosine action by receptor agonists or inhibitors of cellular reuptake and inactivation showed neuroprotection. The up-regulation of adenosine A1-receptor number and affinity by chronic preadministration of the competitive antagonist caffeine also attenuated ischemic brain damage. The mechanisms underlying the neuroprotective effects of adenosine seem to involve both types of adenosine receptors, A1 and A2, but the A1-mediated pre- and postsynaptic neuromodulation may be of special importance. By inhibiting neuronal Ca2+ influx, adenosine counteracts the presynaptic release of the potentially excitotoxic neurotransmitters glutamate and aspartate, which may impair intracellular Ca2+ homeostasis via metabotrophic glutamate receptors or induce uncontrolled membrane depolarization via ion channel-linked glutamate receptors, especially of the N-methyl-D-aspartate (NMDA) type. In addition, adenosine directly stabilizes the neuronal membrane potential by increasing the conductance for K+ and Cl- ions, thereby counteracting excessive membrane depolarization. The latter triggers a number of pathological events including blockade of voltage-sensitive K+ currents, increase of NMDA receptor-mediated Ca2+ influx, and presumably also impairment of glutamate uptake by astrocytes. In the way of a vicious cycle, all these factors again tend to enhance extracellular glutamate levels and membrane depolarization, finally leading to cytotoxic calcium loading and neuronal cell death. In addition to its important neuromodulatory effects, which tend to reduce energy demand of the brain, adenosine acting via A2-receptors in brain vessels, platelets, and neutrophilic granulocytes may improve the cerebral microcirculation and thus oxygen and substrate supply to the tissue. There is evidence that the functional state of adenosine receptors is impaired during ischemia, limiting the time window of the adenosine action.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Adenosine and brain ischemia. 148 19

Metallothionein (MT) protein is readily induced in vivo in rat liver by adenosine and adenosine agonists (2-chloroadenosine, 5-(N-ethyl) carboxamido adenosine, and 5-chloro-5-deoxyadenosine). These presumably operate via AMP/adenosine receptors of the P1 (A2) type, which use the cAMP pathway. ATP was ineffective as an inducer for MT. 2-Chloroadenosine was the most effective inducer (7.27-fold at 11 hr). This induction was blockable by the adenosine antagonists, caffeine and theophylline. MT protein induction by 2-chloroadenosine in primary cultured rat hepatocytes was modest (1.55-fold), but this was also blocked by theophylline. MT mRNA induction was assessed using dot blot and Northern gel assays. Large inductions by 2-chloroadenosine (5.1- to 41-fold) were seen, and these were detectable as early as 2 hr in vivo. Two rat hepatoma cell lines (EC3 and 2M) were studied in vitro. Modest inductions of MT mRNA were seen: 2.10-fold for EC3 and 4.12-fold for 2M. Our studies implicate the potential role of the purinergic system in the modulation of transcription of MT genes in rat liver. The sources of adenosine in vivo that might cause induction of MT mRNA and protein are not well defined, but adenosine may be important as a signal in stress response situations involving tissue damage, such as ischemia, hypoxia, and hemorrhagic shock.
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PMID:Purinergic agonist induction of metallothionein. 152 9

The interrelation between intracellular cAMP content and activity of lysosomal hydrolases was studied in rat liver and heart during ischemia of varying genesis and after recirculation. The activity of acid phosphatase (AP) and cathepsin D (CD) was determined in the fraction enriched with lysosomes (FEL) and in the supernatant fraction (SF) at 30,000 x g. Ischemia of isolated perfused heart of 20 to 60 min as described by Langendorff was accompanied by an increase in the SF/FEL ratio. Postischemic reperfusion resulted in a further increase in this ratio. In a terminal state induced by cardiac arrest of 10 min and within the first postresuscitation hours the SF/FEL ratio in the rat liver also increased. Processing of the liver FEL with 0.025% concentration of detergent Triton X-100 was also indicative of lability of lysosomal membranes during recirculation. The intracellular cAMP content changed differently. During ischemia of the myocardium, the cAMP level rose by 40 min and remained increased after 20 and 40 min of reperfusion. The cAMP content in the liver decreased after 10 min of circulatory arrest and increased in the postresuscitation period achieving its peak 4 h after resuscitation. Intra-abdominal injection of lyposomes with incapsulated cAMP to rats in the postresuscitation period and the study of the effect of dibutyryl-cAMP, caffeine and isoproterenol on the activity of acid hydrolases of ischemic heart and after postischemic reperfusion showed that an increase in the cAMP content achieved in various ways was conducive to stabilization of lysosomal membranes.
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PMID:Role of cAMP in regulation of activity of acid hydrolases of rat heart and liver during ischemia and after recirculation. 166 65

The effects of caffeine on ischemic neuronal injury were determined in rats subjected to forebrain ischemia induced by bilateral carotid occlusion and controlled hypotension (50 mmHg for 10 min). High resolution (100 microns) multi-slice, multi-echo magnetic resonance images were obtained daily for three consecutive days post-operatively in sham-operated rats and in rats that received either saline vehicle (controls), a single i.v. injection of 10 mg/kg caffeine 30 min prior to an ischemic insult (acute caffeine group), or up to 90 mg/kg per day of caffeine for three consecutive weeks prior to an ischemic insult (chronic caffeine group). Rats in the control group exhibited enhanced magnetic resonance image intensity in the striatum 24 h after ischemia which increased in the striatum and also appeared in the hippocampus after 48 h, and which began to resolve in both regions by 72 h post-ischemia. Histopathological analysis of each rat following the final magnetic resonance examination showed that ischemic neuronal injury was strictly confined to the brain regions showing magnetic resonance image changes. Acute caffeine rats showed accelerated changes in the magnetic resonance images, with increased hippocampal intensity appearing at 24 h post-ischemia. Although there was magnetic resonance evidence of accelerated injury, quantitative analysis of the histopathological data at 72 h showed no significant difference in the extent of neuronal injury in any brain region between control-ischemic and acute caffeine rats. Nine out of 11 rats in the chronic caffeine group showed no magnetic resonance image changes over the three study days. Chronic caffeine rats had significantly less neuronal damage in all vulnerable brain regions than either of the other groups of ischemic rats. The accelerated ischemic injury in rats treated with an acute dose of caffeine may occur secondary to antagonism of adenosine receptors, whereas protection from ischemic injury following chronic administration of caffeine may be mediated by up-regulation of adenosine receptors.
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PMID:The effects of caffeine on ischemic neuronal injury as determined by magnetic resonance imaging and histopathology. 186 72

The effects on sarcoplasmic reticulum (SR) Ca2+ transport of solutions mimicking the important intracellular milieu changes associated with short-term hypoxia (hypoxic solutions, as described by Kammermeier et al. J. Mol. Cell. Cardiol. 14: 267, 1982) were examined. SR Ca2+ content was estimated by measuring the magnitude of the caffeine-induced contracture in saponin-skinned rat papillary muscle. SR Ca2+ uptake was inhibited by hypoxic solutions only at loading times less than or equal to 30 s. This inhibition was primarily due to the increase in Pi. The hypoxic solutions had no effect on Ca(2+)-induced Ca2+ release from the SR. We also tested the effects of ATP-free (rigor) solutions that mimic the intracellular environment during late hypoxia and ischemia. Elevating Pi or ADP alone in rigor solution had no effect on SR Ca2+ content. However, elevating Pi and ADP (+/-Mg2+) produced a 44-48% reduction in SR Ca2+ content. This reduction is most likely due to reversal of the SR Ca2+ pump. We conclude that the changes in milieu with short-term hypoxia can depress contractility in intact cardiac muscle by inhibiting SR Ca2+ uptake. During long-term hypoxia or ischemia, these milieu changes can elevate intracellular Ca2+ by reversing the SR Ca2+ pump.
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PMID:Intracellular milieu changes associated with hypoxia impair sarcoplasmic reticulum Ca2+ transport in cardiac muscle. 188 12

The hypothesis that low concentrations of strophanthidin may decrease contractile force (and intracellular sodium activity, aiNa) under normal conditions but might increase force (while still decreasing aiNa) under conditions of increased Ca load was tested in sheep cardiac Purkinje fibers perfused in vitro. Strophanthidin was used at concentrations (7.5-25 nM, "low strophanthidin") that decreased both force and aiNa in different preparations. A marked reduction in flow rate of Tyrode solution ("ischemia") increases aiNa and increases and eventually decreases force: during ischemia, low strophanthidin decreases aiNa but increases force. High [Ca]o (16.2 mM) and norepinephrine (10 nM) increase force and decrease aiNa: in their presence, low strophanthidin decreases aiNa further but increases force. Caffeine (4 mM) decreases force and increases aiNa, and low strophanthidin increases force while having little effect on the increase of aiNa. In ventricular trabeculae, strophanthidin decreases force under basal conditions but increases force during ischemia or Ca overload. Thus, strophanthidin decreases force by lowering aiNa under normal conditions, but it increases force in spite (and perhaps because) of the decrease in aina under conditions of increased calcium load.
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PMID:On the mechanism of the positive inotropy of low concentrations of strophanthidin. 192 Jan 15

Ergotamine tartrate and caffeine has been widely prescribed for the prevention and treatment of migraine headaches. Rarely the ergotamine can cause symptoms of peripheral vascular insufficiency, often concerning the lower extremities. A case report of bilateral severe ischemia to the upper limbs, caused by a chronic assumption of ergotamine tartrate is presented.
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PMID:Spasm of arm arteries due to ergotamine tartrate. A case report. 207 75

Different caffeine and calcium concentrations have been studied for their influence on Ca2(+)-pumping function of sarcoplasmic reticulum in a homogenate from control and ischemic rat myocardium. Ca2(+)-transporting system of sarcoplasmic reticulum terminal cisternae membranes from the ischemic myocardium was found to be more sensitive to Ca2+ and caffeine action, inhibiting Ca2+ uptake velocity, as compared to control. This may be one of causes leading to the contractibility disorder under myocardium ischemia.
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PMID:[The effect of total ischemia on the Ca2+-transporting activity of the sarcoplasmic reticulum of the rat myocardium]. 217 87

This study was designed to examine the effects of hypoxia, acidosis, glucose-free medium and their combination on contraction and sarcoplasmic reticulum (SR) function in rat ventricular trabeculae. The isometric twitch tension was measured during superfusion with hypoxic (PO2 less than 30 mmHg), acidic (pH 6.80), glucose-free, or their combined ("ischemic") Tyrode's solution at 20 degrees C. The time needed to fully recover the contraction induced by 10 mM caffeine (repriming time) was measured to indirectly estimate the Ca2+ uptake of the SR. In "ischemia" and acidosis, the peak developed tension decreased progressively for the first 30 min (37.6 +/- 9.2% and 56.6 +/- 8.4% of control at 30 min, respectively), and then became steady. In hypoxic solution, the peak developed tension decreased moderately for the first 30 min (86.8 +/- 4.8% of control at 30 min), and thereafter remained steady. Developed tension did not change significantly during 60 min of superfusion with glucose-free solution. The repriming time of caffeine contraction was significantly delayed in both "ischemic" and hypoxic solutions, but was unchanged in acidic and glucose-free solutions. These results lead us to suggest that depressed SR function to accumulate Ca2+ may contribute to the decline in tension in ischemia and hypoxia, but that other mechanisms are important in the tension decline induced by acidosis.
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PMID:Effects of hypoxia, acidosis, and simulated ischemia on repriming of caffeine contracture in rat myocardium. 223 37

Intestinal ischemia induced by cocaine abuse is a rare condition. To this date, only three cases have been described. The diagnosis of bowel ischemia should be suspected whenever a cocaine addict has severe abdominal pain. A pathological examination of the resected bowel segment was performed in one case, and the diagnosis was confirmed microscopically. However, the existence of pathologic alterations of the intestinal vessels was not confirmed. Why the intestinal injury is segmental and whether it is related to the dose ingested, the administration route, or the combination of cocaine with alcohol, caffeine, or marijuana remain unclear. The authors report one fatal case associated with cocaine-alcohol overdose. The postmortem examination demonstrated the existence of segmental intestinal ischemia. Microscopic study failed to demonstrate thrombosis in the mesenteric vessels; however, we found an unusual lesion affecting the arterioles located in the intestinal submucosa of the hemorrhagic areas.
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PMID:Vascular lesions in intestinal ischemia induced by cocaine-alcohol abuse: report of a fatal case due to overdose. 234 87


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