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)

In isolated porcine and canine coronary artery and vein short-lasting exposure (8 min) to hypoxia (pO2 less than 20 mm Hg) evoked an increase of tone (6-34% of maximum contraction to potassium chloride). In arterial preparations of both species this response was significantly more pronounced in endothelium-intact vessels as compared to rubbed ones. Reintroduction of oxygen produced a posthypoxic dilation in coronary artery and a posthypoxic contraction in coronary vein. The latter was significantly higher in intact veins of the pig compared to the rubbed preparation but did not differ in canine veins. Repeated exposure to hypoxia with 1 h intervals of rest evoked mostly increased hypoxic and posthypoxic responses. The time of onset of hypoxic contraction was significantly shorter in intact canine coronary artery as compared to the rubbed preparation. The effects of indomethacin (inhibitor of cyclooxygenase), BM 13,505 (thromboxane A2 receptor antagonist) and D 600 (calcium entry blocker) differed in dependence on the response, the vessel and the species tested. Hypoxic contraction in canine coronary artery seems to be more sensitive to blockade of calcium entry whereas hypoxic contraction in porcine coronary artery and hypoxic contraction and posthypoxic contraction in coronary vein of both species are less sensitive to external calcium entry and probably mediated by products of the cyclooxygenase pathway of arachidonic acid. It is suggested that hypoxic and posthypoxic contraction might play a role in redistribution of blood flow from hypoxic to normoxic tissue of the heart during ischemia.
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PMID:Hypoxic and posthypoxic responses in isolated coronary arteries and veins: role of endothelium. 215 Dec 47

Arachidonic acid metabolites have been implicated in the development of cerebral edema following ischemia. To define the time course of metabolite production, subtemporal craniectomies were performed on 60 male Sprague-Dawley rats (350-400 g). Thirty rats underwent middle cerebral artery occlusion while 30 rats underwent craniectomy alone. Five rats in each of two groups (middle cerebral artery occlusion and sham) were sacrificed at 15 minutes, 1 hour, 4 hours, 1 day, 3 days, and 6 days. The cerebral hemispheres were removed and divided in the midsagittal plane. Each hemisphere was immediately frozen in isopentane cooled in dry ice and stored at -70 degrees C. Tissue prostaglandins E2 and 6-keto F1 alpha, and leukotrienes (LT) B4 and C4 were measured by radioimmunoassay. Prostaglandin E2 and 6-keto prostaglandin F1 alpha were significantly elevated at 15 minutes in the middle cerebral artery occlusion hemispheres (p less than 0.05). Prostaglandins were not significantly elevated after 15 minutes. LT B4 and C4 were never significantly elevated. Meclofenamate, a nonsteroidal anti-inflammatory agent, was administered to 21 additional rats. Seven controls underwent middle cerebral artery occlusion alone, 7 were given intraperitoneal meclofenamate (20 mg/kg) 30 minutes prior to middle cerebral artery occlusion, and 7 underwent middle cerebral artery occlusion followed immediately by intraperitoneal meclofenamate (20 mg/kg). The animals were sacrificed at 15 minutes and similarly studied. There was a significant reduction of prostaglandin E2 and 6-keto prostaglandin F1 alpha following pretreatment with meclofenamate (p less than 0.01 and p less than 0.05). In pretreated rats, leukotrienes were not affected by meclofenamate. Similarly, prostaglandins and leukotrienes did not change when meclofenamate was administered after middle cerebral artery occlusion. We conclude that cyclo-oxygenase metabolite production begins within 15 minutes of middle cerebral artery occlusion. Treatment with meclofenamate prior to middle cerebral artery occlusion significantly reduced cyclooxygenase metabolite production, suggesting a protective effect of meclofenamate against ischemia-induced elevations of vasoactive prostaglandins implicated in the development of cerebral edema. Lipoxygenase metabolite production was not affected by middle cerebral artery occlusion or pharmacological intervention.
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PMID:Arachidonic acid metabolite production following focal cerebral ischemia: time course and effect of meclofenamate. 215 40

The activation and accumulation of leukocytes during inflammatory processes such as that initiated by myocardial ischemia and reflow appear to be major determinants of irreversible tissue injury. Myocardial salvage by dual cyclooxygenase/lipoxygenase inhibitors and selective 5-lipoxygenase inhibitors has suggested a role for lipoxygenase (LOX) products, such as the potent chemotactic factor leukotriene B4, in ischemia-reflow injury. However, many LOX inhibitors are antioxidants and several have been shown to directly inhibit neutrophil function in vitro, thereby questioning the role of LOX products in reperfusion injury. To clarify further the protective mechanism of lipoxygenase inhibitors, we have examined the effects of two nonantioxidant inhibitors, SK&F 86002 and REV-5901, on human neutrophil activation and function in vitro. The antioxidant LOX inhibitor nordihydroguiaretic acid, which served as a positive control, exhibited a concentration-dependent inhibition of N-formyl-methionyl-leucyl-phenylalanine (fMLP) and recombinant C5a-induced neutrophil bipolarization, fMLP-induced upregulation of the adherence glycoprotein Mac-1 (CD11b/CD18), fMLP-induced aggregation and neutrophil adherence to and migration through interleukin-1-stimulated human endothelial monolayers. In contrast, neither SK&F 86002 nor REV-5901 (in concentrations up to 50 microM) had any effect on these functions, nor did they inhibit neutrophil oxidative metabolism (phorbol myristate acetate-induced chemiluminescence). Inasmuch as both of these agents have been observed to reduce myocardial ischemia-reflow injury in vivo, their failure to directly inhibit neutrophil function further supports an important role for chemotactic LOX products in the pathogenesis of reperfusion injury.
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PMID:Comparison of antioxidant and nonantioxidant lipoxygenase inhibitors on neutrophil function. Implications for pathogenesis of myocardial reperfusion injury. 215 49

We review below published studies of endothelium-dependent vasodilation in vivo. Endothelium-dependent vasodilation has been demonstrated in conduit arteries in vivo and in the cerebral, coronary, mesenteric, and femoral vascular beds as well as in the microcirculation of the brain and the microcirculation of cremaster muscle. The available evidence, although not complete, strongly suggests that the endothelium-derived relaxing factor generated by acetylcholine in the cerebral microcirculation is a nitrosothiol. The endothelium-derived relaxing factor generated by bradykinin in this vascular bed is an oxygen radical generated in association with enhanced arachidonate metabolism via cyclooxygenase. In the microcirculation of skeletal muscle, on the other hand, the vasodilation from bradykinin is mediated partly by prostacyclin and partly by an endothelium-derived relaxing factor similar to that generated by acetylcholine. Basal secretion of endothelium-derived relaxing factor is controversial in vivo but is usually present in vitro. On the other hand, it appears that endothelium-derived relaxing factor mediates flow-dependent vasodilation in both large vessels and in the microcirculation in vivo. The generation and release of endothelium-derived relaxing factor from endothelium may be abnormal in a variety of conditions including acute and chronic hypertension, atherosclerosis, and ischemia followed by reperfusion. Several mechanisms for these abnormalities have been identified. These include inability to generate endothelium-derived relaxing factor or destruction of endothelium-derived relaxing factor by oxidants after its release in the extracellular space. These abnormalities in endothelium-dependent relaxation may contribute to the vascular abnormalities in these conditions.
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PMID:Endothelium-derived relaxing factors. A perspective from in vivo data. 217 Feb 74

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

The effect of 48 hours of hypothermic renal ischemia utilizing Euro-Collins flush and short term reperfusion on renal prostaglandin synthesis was studied in dogs. Hypothermic ischemia followed by 60 minutes of reperfusion in-vivo resulted in significant elevations in renal Thromboxane B2 (TXB2) production in the outer cortex, inner cortex, and medulla, relative to non-ischemic kidneys. Prostaglandin E2 (PGE2) and 6-keto Prostaglandin F1 alpha (6-K PGF1 alpha) production were not significantly affected by ischemia and reperfusion. Enhanced TXB2 production was not seen with ischemia alone (without reperfusion) or with reperfusion with O2 saturated buffer, indicating a blood born source or stimuli. Early postreperfusion renal blood flow after hypothermic ischemia followed a biphasic pattern; blood flow increased for the first 10 minutes of reperfusion to achieve normal values, and then steadily declined over the next 20 minutes. This pattern was not altered by the cyclooxygenase inhibitors Idomethacin (5 mg/kg, P.O.) or Mefenamic acid (10 mg/kg, I.V.). Administration of the TXA2 synthesis inhibitor CGS-12970 (3 mg/kg, I.V.) or the TXA2/endoperoxide receptor antagonist SQ-29548 (80 micrograms/min, I.A.) significantly increased renal blood flow during reperfusion but neither agent altered the basic time dependent pattern observed in the control group. These data indicate that 48 hours of hypothermic renal ischemia results in dramatic changes in intrarenal TXA2 synthesis at the time of reperfusion. Enhanced TXA2 production is not dependent on reoxygenation per se, but rather requires reperfusion with blood suggesting a circulatory source.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostanoids and hypothermic renal preservation injury. 228 Nov 20

Neutrophils have been implicated in the genesis of myocardial ischemia-reperfusion injury, and their mechanism of action has been linked to the production of reactive oxygen species, fatty acid-derived prostanoids, and leukotrienes. In this study, we examined the potential relation between production of reactive oxygen species and cyclooxygenase-derived autacoids by studying the effects of superoxide dismutase (SOD) and catalase (CAT) on the rise in thromboxane formation observed with myocardial ischemia and reperfusion. Immunoreactive thromboxane B2 was measured in cardiac lymph from conscious dogs during reperfusion after a 60-minute occlusion in the presence of infusions of SOD alone, CAT alone, and a combination of SOD and CAT. Reperfusion after 60 minutes of ischemia causes an immediate elevation in thromboxane B2. SOD and CAT infusion prevented this rise in thromboxane B2 as did infusion of SOD alone. The ability of SOD-CAT to suppress thromboxane B2 production dissipated within 3 hours after the cessation of infusion, at which time thromboxane B2 excretion increased. The modulation of fatty acid oxygenases by reactive oxygen species may be a very important pathogenic factor in considering the origin of the protective effect of antioxidants in the setting of myocardial ischemia-reperfusion injury.
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PMID:Thromboxane B2 in cardiac lymph. Effect of superoxide dismutase and catalase during myocardial ischemia and reperfusion. 231 86

The anti-ischemic effects of nafazatrom (10 mg/kg intraduodenally) have been studied in a canine model of myocardial infarction. Nafazatrom was given 30 min before and 2 h after occlusion of the left anterior descending coronary artery (LAD). Effects were compared with those after intravenous indomethacin (10 mg/kg) treatment. Infarct size was measured at 6 h of coronary occlusion by postmortem tetrazolium staining. Myocardial ischemia was reduced after nafazatrom administration, whether related to total left ventricle (18 +/- 3.3 vs. 30.7 +/- 4.8%; p less than 0.05) or to the LAD vessel area at risk for infarction (51.4 +/- 4.0 vs. 82.5 +/- 4.5%; p less than 0.01). Salvage with nafazatrom occurred in the subepicardial and endomural tissues without lateral protection. Indomethacin had no effects on infarction. The LAD occlusion-induced hemodynamic consequences were reduced at 15 min by nafazatrom and remained unchanged by indomethacin. During the following experimental course, no differences were noted between the groups. At 6 h, blood flow in the nonoccluded circumflex artery increased by 12.6 +/- 3.2 ml/min (p less than 0.05) following nafazatrom treatment. Thus, nafazatrom reduced ischemia by a mechanism unrelated to changes in hemodynamics. Most likely, this was due to 5-lipoxygenase inhibition. This may shift arachidonic acid metabolism to cyclooxygenase products and prevent release of deleterious lipoxygenase products by neutrophils during ischemic injury.
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PMID:Effects of nafazatrom and indomethacin on experimental myocardial ischemia in the anesthetized dog. 241 12

Recent investigations in several organs indicate cytoprotective effects of prostanoids. For further elucidation of this efficacy the investigations dealt with the cardioprotection of prostanoids (iloprost, PGE1) and the cyclooxygenase inhibitor indomethacin under in vivo- and in vitro-conditions. The experiments were carried out in isolated perfused guinea pig hearts and anaesthetized rabbits. Cardiac damage was induced by chemical substances or loading by aortic constriction or ischemia. In isolated perfused hearts iloprost and indomethacin suppressed the toxic effects of carbon tetrachloride, chloroform, benzene, sodium dithionate and phenylethylbarbituric acid, but not the efficacy of quinine sulfate and 2,4-dinitro-phenol. Cardiac loading by aortic stenosis or ischemia induced a decrease of contractility and blood pressure and changes in the myocardial PGI2-biosynthesis. On the other side application of indomethacin, iloprost or PGE1 diminished the cardiac damage and inhibit the myocardial PGI2-formation. The results show that indomethacin and prostanoids have a protective effect in pathophysiological changes or toxic damage of the heart, possibly caused by a stabilization of the cellular membrane.
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PMID:Significance of the cardioprotective effect of prostanoids and indomethacin. 247 Mar 59

Static contraction of hind-limb muscles is well known to increase reflexly cardiovascular function. Recently, blockade of cyclooxygenase activity has been reported to attenuate the reflex pressor response to contraction, a finding which suggests that working skeletal muscle releases arachidonic acid metabolites. Therefore, we measured the effects of static contraction and ischemia on arachidonic acid levels in the gastrocnemius muscles of barbiturate-anesthetized cats treated with indomethacin. Unesterified arachidonic acid levels were measured by high-pressure liquid chromatography. We found that static contraction of freely perfused gastrocnemius muscles increased arachidonic acid levels from 4.4 +/- 1.0 to 10.3 +/- 2.2 nmol/g wet wt (n = 12; P less than 0.005). Likewise, static contraction of gastrocnemius muscles made ischemic for 2 min before the onset of the contraction period increased arachidonic acid levels from 12.6 +/- 2.3 to 21.0 +/- 2.0 nmol/g wet wt (n = 12; P less than 0.01). Lastly, 2 min of ischemia with the gastrocnemius muscles at rest increased arachidonic acid levels from 5.9 +/- 1.1 to 10.5 +/- 3.0 nmol/g wet wt (n = 18; P less than 0.02). We conclude that both static contraction and ischemia increase arachidonic acid levels in working hindlimb muscle.
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PMID:Static contraction increases arachidonic acid levels in gastrocnemius muscles of cats. 250 Dec 90


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