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)

SC-29333 (SC) has been reported to protect the gastric mucosa from the effects of topical aspirin. We compared SC and 16,16-dimethyl PGE2 (16-dm) in 20 chambered canine stomachs (6 controls and 7 of each PG). Prostaglandin was added to an acid solution (100 mM HCl; 54 mM NaCl) at 0, .001, .01, 0.1, and 1.0 microgram/ml (two periods each). Then aspirin (20 mM) and PG (1.0 microgram/ml) (two periods) were followed by hemorrhagic shock (near 60 mm Hg mean arterial pressure). 16-dm caused a significant efflux of fluid (-6.5 +/- 5.3 to 17.3 +/- 6.7 microliters/min), Na+ (2.1 +/- 0.5 to 6.8 +/- 1.6 muEq/min), and Cl- (-0.9 +/- 2.4 to 5.3 +/- 1.3 muEq/min), but did not affect K+ or H+. 16-dm also caused a slight drop in potential difference (PD) (67.6 +/- 1.7 to 60.3 +/- 2.0 mV). 16-dm did not significantly affect total blood flow. Percent lesion formation was more severe than controls (20.2 +/- 3.5 vs 11.6 +/- 1.7 percent) but not statistically significant. SC had no significant effect on fluid, H+, Na+, K+, or Cl-. It caused an increase in blood flow (6.85 +/- 1.46 to 26.20 +/- 2.74 ml/min, p less than .001). SC significantly reduced percent lesion formation (1.9 +/- 0.9% p less than .001). We conclude: 1) SC causes an increase in mucosal blood flow and protects from aspirin-shock ulcerogenesis. 2) 16-dm stimulates an efflux of non-parietal extracellular fluid and fails to protect against aspirin injury during mucosal ischemia. 3) SC cytoprotection may be mediated by increased mucosal blood flow. 4) The mechanism of cytoprotection with 16-dm may require sufficient mucosal blood flow for filtration of non-acid fluid from blood to gastric lumen.
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PMID:The cytoprotective effects of (+/-)-15-deoxy-16-alpha, beta-hydroxy-16-methyl PGE1 methyl ester (sc-29333) versus aspirin-shock gastric ulcerogenesis in the dog. 679 83

A brief review of the pharmacology, pharmacokinetics, and metabolism of buflomedil-HCl is presented providing a pharmacologic basis for buflomedil therapy of ischemia associated with peripheral vascular disease. Buflomedil is readily absorbed in the gastrointestinal tract and has a plasma half-life of approximately 2-3 hours. The para-desmethyl derivative of buflomedil has been identified as a urinary metabolite. Pharmacologically, buflomedil increases perfusion to impaired vascular beds of the microcirculation, increases arterial perfusion with minimal effects on central hemodynamics, exhibits apparent oxygen "sparing" effects in animal experiments, demonstrates inhibitory effects on platelet aggregation, and, in preliminary experiments, appears to improve deformability of erythrocytes with abnormal fluidity. A nonspecific alpha-receptor blocking activity appears to be involved, at least in part, in these pharmacologic effects. The relative importance of these mechanisms/effects in the treatment of symptoms of vascular disease is unknown.
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PMID:An experimental overview of a new vasoactive drug: buflomedil HCl. 703 90

Myocardial protection of dilazep HCl, which is an antianginal drug and a potent calcium antagonist against myocardial damage following acute ischemia and reperfusion, was studied on myocardial contractility in isolated blood perfused canine left ventricular muscle. Myocardial function was expressed by percent recovery rate of maximum net developed tension. 1. The coronary infusion of dilazep revealed significant myocardial protection during normothermic ischemic arrest of 45 min and reperfusion. 2. The i.v. administration of dilazep to the donor dog and Young's infusion also showed significant myocardial protection during normothermic ischemic arrest of 45 min and reperfusion. 3. The combination of i.v. administration of dilazep to the donor dog, Young's infusion, and hypothermia showed significant myocardial protection during prolonged ischemia and reperfusion even in hypertrophied ventricle. 4. Dilazep prevents abnormal calcium accumulation in myocardial cells during reperfusion. These results demonstrate that dilazep provides effective myocardial protection during ischemic arrest and reperfusion, and they may support its clinical application as a myocardial protective agent for open-heart surgery.
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PMID:[Myocardial protection by dilazep in myocardial ischemia and reperfusion]. 719 72

Effects of short-term ischemia on chemoreceptor responses to various stimuli and ultrastructural features of the carotid body of the cat were examined. Total occlusion of the arteries supplying the carotid body induced an increase in chemoreceptor discharges. After 1-hr ischemia, chemoreceptor responses to NaCN and asphyxia were markedly depressed to 10-40% of the control, while those to ACh and HCl were not greatly affected. Prolonged ischemia (2-3 hr) produced a marked decrease in responsiveness to all stimuli. One-hr ischemia induced changes in the ultrastructural appearance of the glomus cell, including a decrease in the number of dense-cored vesicles, the appearance of swollen or vacuolated mitochondria and amorphous substances, while the nerve ending showed a relatively well-preserved appearance. Prolonged ischemia (2-3 hr) produced degenerative changes both in the glomus cell and nerve ending; vacuolation, a marked decrease in electron density of cytoplasmic matrix of the glomus cell and nerve ending, and marginal shrinkage of the nuclei. The results indicate that the markedly depressed responses to NaCN and asphyxia after 1-hr ischemia are due to dysfunction of the glomus cell, while ACh and HCl, acting directly on the nerve ending which was not greatly affected by ischemia, evoked well-preserved responses in the chemoreceptors.
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PMID:Alteration of chemoreceptor responses and ultrastructural features of ischemic carotid body of the cat. 732 17

Ischemia of the gastric epithelium has emerged as one of the more likely mechanisms for gastric ulceration. Radiolabeled microspheres (15 mu) were used to measure blood flow to exteriorized, chambered stomach segments in eight dogs during the development of aspirin erosions. Flow determinations were made before aspirin (20 mM in 140 mM HCl) exposure and at 2, 10, and 20 minutes after the initiation of the chemical insult. Lesions formed at 30 minutes of acetylsalicylic acid exposure. The epithelium was separated into normal and injured, based on gross discoloration caused by intramucosal hemorrhage. The calculated blood flows to the abnormal and normal mucosa were identical at 2 minutes (0.22 +/- 0.04 versus 0.15 +/- 0.03, NS) and at 10 minutes (0.39 +/- 20 versus 0.17 +/- 0.04, NS) after initiation of aspirin injury (all values in ml/gram-wet weight/min, mean +/- SEM). By 20 minutes of aspirin exposure, mucosal blood flow to areas that eventually became injured was greater than the blood flow to areas that remained normal (0.45 +/- 0.12 versus 0.13 +/- 0.05 P less than 0.05). The data suggest that ischemia does not play a role in chemical erosive gastritis.
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PMID:Focal microcirculatory changes during the production of aspirin-induced gastric mucosal erosions. 746 23

alpha-Adrenergic receptor responsiveness has been reported to increase during myocardial ischemia, correlating with onset of malignant arrhythmias. If alpha-adrenoceptor mechanisms play a significant role in induction of life-threatening arrhythmias, inhibition of these receptors with specific alpha-adrenoceptor antagonists should protect against disturbances in cardiac rhythm. To test this hypothesis, we induced ventricular fibrillation (VF) in 21 mongrel dogs with healed myocardial infarctions (MI) by 2-min coronary artery occlusion during exercise. On a subsequent day, the exercise plus ischemia test was repeated after the alpha 1-adrenoceptor antagonist prazosin HCl (0.5 mg/kg intravenously, i.v.; n = 14) or the alpha 1A-adrenergic receptor subtype antagonist WB4101 (2.0 mg/kg i.v., n = 9). Prazosin elicited a significant reduction in left ventricular systolic pressure (LVSP, control 157.0 +/- 6.5 vs. prazosin 118.5 +/- 2.7 mm Hg) and prevented arrhythmias in 13 of 14 animals (chi square p < 0.001). No other hemodynamic parameters, either before or during the coronary occlusion, were altered by prazosin. WB4101 did not alter any hemodynamic parameters either before or during coronary artery occlusion, yet prevented VF in 7 of 9 animals (chi square p < 0.025), delaying onset of malignant arrhythmias in the remaining animals. A second control exercise plus ischemia test reproducibly induced VF in all animals. Together these data demonstrate that alpha-adrenoceptor antagonists can prevent VF independent of hemodynamic changes. In particular, the data suggest that activation of the alpha 1A-adrenergic receptor subtype may contribute importantly to development of malignant arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of alpha 1-adrenergic receptor antagonists on susceptibility to malignant arrhythmias: protection from ventricular fibrillation. 752 95

Rebamipide (2-(4-chlorobenzoylamino)-3-[2-(1H)-quinolinon-4-yl] propionic acid), a novel antiulcer agent, has been reported to prevent various acute experimental gastric mucosal lesions and to accelerate the healing of chronic gastric ulcers. We investigated the effect of rebamipide on rat gastric mucosa damaged by exposure to 30 min of ischemia and 60 min of reperfusion (I/R) with continuous intragastric instillation of 0.1 N HCl (1 ml/100 g body weight) into the stomach. Rebamipide, at 30 and 100 mg/kg, i.p., reduced the mucosal damage score from 2.28 (I/R vehicle group) to 1.54 and 1.07, respectively. Pretreatment with rebamipide significantly reduced the activity of myeloperoxidase (an index of neutrophil infiltration) and preserved the activities of superoxide dismutase and nitric oxide synthase in the gastric mucosa with inhibition of malondialdehyde production. Thus, a negative correlation between the activities of nitric oxide synthase and myeloperoxidase (y = 4.35-9.45x, r = .67, P < .01) was observed. In an in vitro study, rebamipide inhibited N-formyl-met-leu-phe-induced chemotaxis of neutrophils and production of superoxide anion from opsonized zymosan-stimulated neutrophils. However, it did not affect the production of superoxide anion either by the xanthine-xanthine oxidase reaction or phorbol 12-myristate 13-acetate-stimulated neutrophils. Based on these results, it is suggested that rebamipide exerts a protective effect on the I/R-induced gastric mucosal damage through inhibition of mobilization and activation of neutrophils in association with an attenuation of the decreases in both superoxide dismutase and nitric oxide synthase activities, thereby preventing the gastric microcirculation from deterioration.
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PMID:Preventive effect of rebamipide on gastric lesions induced by ischemia-reperfusion in the rat. 756 69

2-Amino-N-(1,2-diphenylethyl)-acetamide hydrochloride (FPL 13950) has been demonstrated to have good anticonvulsant efficacy and a relative lack of acute side effects in rodents. Similar in structure to remacemide hydrochloride, it was also shown to possess weak potency as an uncompetitive antagonist of N-methyl-D-aspartic acid (NMDA) receptors. In our study FPL 13950 was profiled preclinically as a potential neuroprotective agent with respect to lengthening the survival time of rodents exposed to hypoxia, as well as for ability to protect the vulnerable CA1 pyramidal neurons of the rat and dog from the consequences of global ischemia. Under conditions of hypoxia, pretreatment of rodents with FPL 13950 resulted in an extension in the time to loss of the righting reflex (rats) and mortality (rats and mice). This occurred whether the rats were maintained at ambient body temperature or made hyperthermic. When administered after 30 min of four-vessel occlusion global ischemia for periods of either 7 (b.i.d.) or 14 days (s.i.d.), FPL 13950 exhibited protection of the vulnerable CA1 hippocampal neurons in rat. In the 14-day treatment study the CA3 neurons were evaluated and FPL 13950 was found to prevent the lesser degree of ischemic-induced damage to this hippocampal region. In ischemic rats treated with FPL 13950 for 7 days, electrophysiological responses of CA1 neurons (orthodromic and antidromic population spikes, in vitro) were also preserved after FPL 13950 treatment. FPL 13950 was administered i.v. at 30 min after 8 min of clamping the ascending aorta in dogs, followed by a b.i.d./s.i.d. dosing regimen for 1 wk. Neuronal damage to CA1 was considerable in the saline-treated ischemic animals but significantly protected in dogs receiving FPL 13950. FPL 13950 continues to serve as a potential backup candidate for remacemide HCl which is currently in clinical trials for patients with stroke and epilepsy.
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PMID:Neuroprotective actions of 2-amino-N-(1,2-diphenylethyl)-acetamide hydrochloride (FPL 13950) in animal models of hypoxia and global ischemia. 763 64

Spatial alterations in blood flow during the development of mucosal injury induced by ischemia-reperfusion in rats were determined with a two-dimensional laser Doppler tissue perfusion imager. The rats were anesthetized with pentobarbital, and the stomach was exteriorized on a stage; the mucosa was then sequentially scanned. The mucosa was constantly superfused with 0.1 N HCl in physiological saline. Systemic arterial pressure was continuously monitored and blood was stepwisely withdrawn from the femoral artery by 20-mmHg stage and then maintained at 20 mmHg for 20 min. The shed blood was reinfused and the stomach was removed 30 min later. Under control conditions, the average perfusion of the forestomach was usually greater than that in the glandular stomach. When systemic blood pressure was stepwisely decreased, the extent of decrease in the mucosal blood perfusion unit was always greater than that in systemic blood pressure, but mucosal perfusion appeared to be uniformly decreased throughout the stomach. Ten min after reperfusion, a hypoperfused area began to appear in the corpus near the greater curvature, and this area subsequently increased. The area of ulcer formation corresponded with the hypoperfused area in the gastric mucosa 30 min after reperfusion. Pretreatment with CV-6209, a platelet-activating factor antagonist, significantly attenuated the hypoperfusion induced by reperfusion and also prevented gastric mucosal damage. Our results suggest that hypoperfusion in the mucosal microcirculation is indeed an important factor contributing to the localized occurrence of gastric mucosal lesions and that the laser Doppler perfusion imager is useful for the detection of local hypoperfused areas in the gastric mucosa.
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PMID:Spatial heterogeneity of mucosal blood flow during ischemia-reperfusion injury of rat stomach investigated by laser Doppler perfusion imaging. 764 92

Moyamoya disease is a cerebrovascular disease characterized radiologically by progressive narrowing and occlusion of the arteries contributing to the circle of Willis and its branches. There is formation of an exuberant collateral network of blood vessels at the base of the brain, which is thought to arise in response to chronic ischemia. Clinically, the course is variable, with patients having repeated transient ischemic attacks, strokes, migraine, and seizures. Effective treatment is not available. The etiology and pathophysiology of moyamoya disease are largely unknown. Two patients with arteriographically proven moyamoya disease were identified. Both patients were symptomatic before age 5 years. Despite successful encephaloduroarteriosynangiosis revascularization procedures, they continued to experience an inexorable downhill course. A calcium channel blocker (nicardipine HCl) was introduced in order to prevent further symptoms. After the introduction of nicardipine, no further strokes occurred in either patient. There were no further episodes of transient ischemic attacks, seizures, or headache in one patient and decreased frequency in the other. In patients with moyamoya disease, nicardipine may have a beneficial effect on cerebral hemodynamics and may prevent ischemic sequelae by optimizing existing collateral circulation.
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PMID:Use of a calcium channel blocker (nicardipine HCl) in the treatment of childhood moyamoya disease. 782 27


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