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)

Patient care and research in clinical vascular surgery have traditionally and appropriately focused on the complications of atherosclerosis. Without question, however, the clinical field of vascular surgery encompasses a number of areas other than clinical vasospasm as exemplified by Raynaud's syndrome. At the Clinical Research Center at the Oregon Health Sciences University, during the past 20 years the vascular surgery unit has maintained an active research program in Raynaud's syndrome and to date has enrolled and longitudinally followed more than 1000 patients with this affliction. There has been an opportunity to participate in the long-term management of this large population with emphasis both on natural history and vascular laboratory diagnosis and treatment. Raynaud's syndrome is a condition characterized by episodic digital ischemia in response to cold or emotional stimuli. The incidence is greater in women, and it is more frequent in areas with a cool, damp climate. Raynaud's usually affects the hands and fingers, but it may affect the feet and toes as well. The classical Raynaud's attack is tricolor and consists of blanching of the digits resulting from cessation of arterial flow, then cyanosis upon rewarming. This is followed by reactive hyperemia, which causes the digits to turn red. Raynaud's syndrome is classified into two groups: vasospastic or obstructive. Vasospastic Raynaud's is generally cold-induced. Nicotine, stress, and caffeine are associated with vasospasm. Obstructive Raynaud's is observed in association with other diseases such as connective tissue disorders, atherosclerosis, traumatic occlusion, Buerger's disease, and occupational related disorders. The diagnosis of Raynaud's is based on differentiating between vasospasm and obstruction and detecting the presence of associated disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Raynaud's syndrome: diagnosis and treatment. 774 70

The teratogenic effect of caffeine has been clearly demonstrated in rodents. The sensitivity of different animals species is variable. Malformations have been demonstrated in mice at 50-75 mg/kg of caffeine, whereas the lowest dose usually needed to induce malformations is 80 mg/kg in rats. However, when caffeine is administered in fractioned amounts during the day, 330 mg/kg/day are necessary to reach teratogenicity in rats. In rodents, the most frequently observed malformations are those of the limbs and digits, ectrodactyly, craniofacial malformations (labial and palatal clefts) and delays in ossification of limbs, jaw and sternum. Nevertheless, even in rodents, caffeine can be considered as a weak teratogenic agent, given the quite large quantities of caffeine necessary to induce malformations and the small number of animals affected. In humans, caffeine does not present any teratogenic risk. The increased risk of the most common congenital malformations entailed by moderate consumption of caffeine is very slight. However, caffeine potentiates the teratogenic effect of other substances, such as tobacco, alcohol, and acts synergistically with ergotamine and propranolol to induce materno-fetal vasoconstrictions leading to malformations induced by ischemia. Therefore, even though caffeine does not seem to be harmful to the human fetus when intake is moderate and spread out over the day, some associations, especially with alcohol, tobacco, and vasoconstrictive or anti-migraine medications should be avoided. Maternal consumption of caffeine affects brain composition, especially in case of a low-protein diet and also seems to interfere with zinc fixation in brain. Maternal exposure to caffeine induces also long-term consequences on sleep, locomotion, learning abilities, emotivity, and anxiety in rat offspring, whereas in humans, more studies are needed to ascertain long-term behavioral effects of caffeine ingestion by pregnant mothers.
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PMID:Potential teratogenic and neurodevelopmental consequences of coffee and caffeine exposure: a review on human and animal data. 786 54

The effects of global ischemia on the contractile system and on sarcoplasmic reticulum (SR) function were studied by measuring the isometric tension and the SR Ca2+ release activity of chemically skinned cardiac fiber preparations from seven patients undergoing open-heart surgery. Ten minutes of ischemia caused 1) a decrease in the myofilament sensitivity to Ca2+ (expected Ca2+ concentration giving half-maximal tension; from 0.69 +/- 0.04 to 1.38 +/- 0.06 microM, n = 7) and in the cooperativity index (Hill coefficient; from 2.61 +/- 0.45 to 0.92 +/- 0.15, n = 7), 2) a decrease in myosin light chain phosphorylation, and 3) a 300% increase in the threshold caffeine concentration for SR Ca2+ efflux channel activation, with a 30% reduction in the rate of Ca2+ release by caffeine at threshold concentrations and a 23% reduction in the rate of release by 20 mM caffeine. After preincubation with 5 microM trifluoperazine, a calmodulin antagonist, the caffeine threshold of ischemic and control cardiac muscle became comparable. Most changes were reversed by reperfusion, while the caffeine threshold was still two times greater than control. These results indicate that ischemia caused alterations of the cardiac muscle contractile apparatus and the SR that were reversed only after reperfusion.
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PMID:Effects of ischemia on sarcoplasmic reticulum and contractile myofilament activity in human myocardium. 823 22

Cardiac sarcoplasmic reticulum (SR) plays an important role in regulation of the intracellular Ca2+ concentration. It is well known that intracellular Ca2+ overload is one cause of reperfusion injury. Thus, it is predicted that reperfusion injury of myocardium can be prevented by eliminating the Ca2+ overload. This study examined the effects of caffeine, a SR blocker, on reperfusion injury in isolated perfused rat hearts. Working hearts were reperfused for 25 min after 30 or 50 min of ischemia. Caffeine (10(-4) M) was administered during the period of ischemia or the initial 5 min of reperfusion. The left ventricular pressure and the electrocardiogram were recorded. Rate-pressure products were calculated as an index of cardiac function. Adenine nucleotides were measured by high-performance liquid chromatography to assess energy charge. The administration of caffeine for a short period during the initial reperfusion significantly improved cardiac function in the hearts. Caffeine pretreatment during 50 min of ischemia, though, resulted in deterioration of both energy charge and cardiac function. Caffeine did not affect the incidence of either ventricular fibrillation or reversion to sinus rhythm. The energy charges were lower in the preparations with sustained ventricular fibrillation.
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PMID:Effects of caffeine on ischemia-reperfusion injury in isolated rat hearts. 824 49

The effects of the sulphonlyurea drugs glibenclamide and tolbutamide were tested upon ATP-sensitive K+ channels activated by dinitrophenol or carbonyl cyanide p-(trifluoromethoxy)-phenylhydrazone (FCCP) in ventricular myocytes isolated from rat hearts. In whole-cell current recording, 1 microM glibenclamide or 1 mM tolbutamide totally but only transiently inhibited the K+ current activated by dinitrophenol or FCCP. In cell-attached membrane patches, 1 to 100 microM glibenclamide initially inhibited the activation of ATP-sensitive K+ channels induced by dinitrophenol or FCCP, but failed to prevent the activation of these channels during contracture. Myocyte contracture induced by caffeine or Ca++ entry during K+ depolarization did not activate ATP-sensitive K+ channels. In excised membrane patches, 1 to 10 microM glibenclamide did not block completely opening of ATP-sensitive K+ channels. Neither intracellular ADP nor phosphorylable substrate were able to reliably influence the effect of glibenclamide. It is concluded that sulphonylurea drugs, otherwise highly effective blockers of this type of ion channel, were no longer able to inhibit the opening of ATP-sensitive K+ channels during the final stages of metabolic stress. These channels could therefore be responsible for both the glibenclamide-sensitive and glibenclamide-insensitive phases of K+ loss during cardiac ischemia.
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PMID:Sulphonylurea drugs no longer inhibit ATP-sensitive K+ channels during metabolic stress in cardiac muscle. 833 72

Sumatriptan, a 5HT1-like receptor agonist, is a completely new treatment principle for migraine. In an extensive international programme of controlled clinical trials, sumatriptan, 6 mg subcutaneously and 100 mg orally, was superior to placebo in reducing headache and associated symptoms. The response rate for subcutaneous sumatriptan (70-84% after 1 h and 81-87% after 2 h) was higher than for oral sumatriptan (50-67% after 2 h). Additional doses did not increase efficacy. Oral sumatriptan was superior to Cafergot (2 mg ergotamine plus 200 mg caffeine) and somewhat better than aspirin (900 mg) plus metoclopramide (10 mg). Recurrence of migraine occurred in approximately 40% of attacks. Side effects were generally mild and short-lived in the controlled clinical trials. However, in clinical practice sumatriptan has subsequently caused rare cases of heart ischemia and sumatriptan is contraindicated in patients with a history of ischemic heart disease.
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PMID:Sumatriptan for the treatment of migraine attacks--a review of controlled clinical trials. 839 70

The mechanism by which thromboxane A2 (TXA2) causes its detrimental actions on the myocardium during ischemia and reperfusion injury is unknown. The present study was designed to investigate the influence of U46619, a stable TXA2 analog, on intracellular Ca transients in electrically stimulated single neonatal rat ventricular myocytes by using spectrofluorometric analysis of fura-2-Ca binding. Administration of U46619 increased basal and peak Ca concentrations as well as width of electrically induced Ca transients in a concentration-dependent manner (0.1-1 microM) during a 1-hr exposure. Exposure to 10 microM U46619 caused irregular Ca transients and a marked increase in cytosolic-free Ca concentration. The effects of U46619 were antagonized by the TXA2 receptor antagonist SK&F95585 (2 microM), dibutyryl cyclic AMP (1 mM), verapamil (1 microM) and ryanodine (1 microM). U46619 did not affect the increase in cytosolic Ca induced by KCl (90 mM) depolarization. Caffeine (10 mM)-induced Ca release from the sarcoplasmic reticulum was enhanced markedly in U46619-treated cells. Significant lactate dehydrogenase leakage from the myocytes did not occur at 1 to 10 microM U46619. These results indicate that the increase in Ca transients by U46619 is a receptor-mediated process leading to a Ca accumulation in the sarcoplasmic reticulum which is likely to be responsible for an enhanced cytosolic Ca during excitation-contraction coupling. Thus, the identification of U46619-induced alterations of Ca dynamics appears to provide, at the cellular level, a direct role for TXA2 during myocardial ischemia and reperfusion.
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PMID:Alterations by a thromboxane A2 analog (U46619) of calcium dynamics in isolated rat cardiomyocytes. 842 35

We investigated the mechanisms by which endotoxic shock induces intrinsic myocardial depression by studying cardiac myocytes isolated from 10 anesthetized instrumented rabbits given 172 +/- 42 (mean +/- SD) micrograms/kg IV endotoxin. Left ventricular (LV) depression developed 4 +/- 1 hours after endotoxin administration, with a 15 +/- 4% increase in LV internal end-systolic diameter, measured with sonomicrometers at a matched LV end-systolic pressure of 65 +/- 10 mm Hg. Normal LV pressure, arterial PO2, and pH were maintained to minimize confounding effects of ischemia, hypoxia, and acidosis. Cardiac myocytes from endotoxin-exposed rabbits had less unloaded cell shortening and lower peak rates of cell shortening (-dL/dt) and lengthening (+dL/dt) at [Ca2+] levels ranging from 0.5 to 16 mM when compared with myocytes isolated from normal rabbits or rabbits undergoing an identical protocol but without exposure to endotoxin. At 2 mM [Ca2+], cell shortening was depressed by approximately 25% because of a decrease in action potential duration (207 +/- 70 versus 375 +/- 64 milliseconds). In contrast, there was only mild impairment of sarcoplasmic reticulum (SR) function. When myocytes were restimulated after rest periods of 4 to 480 seconds, the decrement in cell shortening (rest decay), peak -dL/dt and peak +dL/dt, and the recovery from rest decay were similar in myocytes from endotoxin-treated and normal rabbits. There was a greater decrement in cell shortening in the second beat of postrest recovery in myocytes from endotoxin-treated rabbits than in normal myocytes. This was partly due to a 12% decrement in action potential duration with rest decay, which did not occur in normal myocytes. The SR Ca2+ content assessed by contractures in 10 mM caffeine was similar in the two groups. We conclude that endotoxic shock produces a LV depression in vivo that persists in isolated myocytes studied in vitro. This intrinsic myocardial depression is largely related to endotoxin-mediated sarcolemmal alterations, which shorten action potential duration, and is not due to alterations in SR function.
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PMID:Cellular mechanisms of endotoxin-induced myocardial depression in rabbits. 850 24

The cytokine interleukin (IL)-6 has recently been demonstrated to play a role in the pathology of Alzheimer's disease (AD). The mechanisms leading to increased IL-6 levels in brains of AD patients are still unknown. Because in experimental animals ischemia increases both the levels of cytokines and the extracellular concentrations of adenosine in the brain, we hypothesized that these two phenomena may be functionally connected and that adenosine might increase IL-6 gene expression in the brain. Here we show that the mixed A1 and A2 agonist 5'-(N-ethylcarboxamido) adenosine (NECA) induces an increase in IL-6 mRNA levels and protein synthesis in the human astrocytoma cell line U373 MG. The A1-specific agonists R-phenylisopropyladenosine and cyclopentyladenosine are much less potent, and the A2a-specific agonist CGS-21860 shows only marginal effects. Increased levels of mRNA are already found within 30 min after NECA treatment. The A2a-selective antagonists 8-(3-chlorostyryl) caffeine and KF17837 [(E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine] , which have also some antagonistic properties at A2b receptors, and the nonspecific adenosine antagonist 8-phenyltheophylline were equipotent at inhibiting the NECA-induced increase in IL-6 protein synthesis, whereas the specific A1 antagonist 8-cyclopentyl-1,3 dipropylxanthine is much less potent. The results indicate that adenosine A2b receptors participate in the regulation of the IL-6 gene in astrocytoma cells.
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PMID:Adenosine A2b receptors mediate an increase in interleukin (IL)-6 mRNA and IL-6 protein synthesis in human astroglioma cells. 862 94

Cerebral ischemia of 5 min duration was induced in unanesthetized Mongolian gerbils by bilateral occlusion of the carotid arteries. The extent of ischemic injury was assessed behaviorally by measuring the increases in locomotor activity following ischemia and by a histopathological assessment of the extent of CA1 hippocampal pyramidal cell injury and loss 5 days after ischemia. The A2a adenosine receptor selective antagonists 8-(3-chlorostyryl) caffeine (CSC; 0.1 mg/kg i.p.) and 4-amino-1-phenyl[1,2,4]-triazolo[4,3-a] quinoxaline (CP 66,713; 0.1 mg/kg i.p.) reduced the extent of ischemia-induced injury. An A1 selective receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 1.0 mg/kg i.p.), enhanced ischemia-evoked injury. These results suggest that adenosine A2a receptor antagonists may be useful for the prevention of cerebral injuries resulting from stroke or cardiac arrest.
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PMID:The effects of selective A1 and A2a adenosine receptor antagonists on cerebral ischemic injury in the gerbil. 882 36


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