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

The purpose of the investigation was to determine the minimal duration of transient ischemia which would produce stable myocardial damage. The compression of the anterior branch of the rat left coronary artery during 5, 10, 15, and 20 minutes was used for this purpose. The sizes of necrotic and ischemic areas in the rat myocardium were determined by the differential indicator method and morphometrically 4 and 72 hours after transient ischemia. It was established that 15-min transient occlusion is the most suitable for the above purpose. The ratio of a necrotic to an ischemic area was almost the same 4 and 72 hours after transient occlusion (45.8 +/- 6.9 and 41.1 +/- 8.6%, respectively). An analysis of cardioprotective cytochrome C activity confirms that there is a phenomenon of injury-slowing interventions in the pharmacology of anti-ischemic compounds.
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PMID:[Transient ischemia as a factor in modelling regulated coronarogenic alteration in the myocardium]. 775 70

Biotechnological cytochrome c, heme-tetradecapeptide (HTDP) and animal cytochrome c were studied for their effects on intact and brain ischemic rats. In the latter case, the compounds were administered before ischemia induction and 15 min after artery ligation. It was found that the cytochrome c preparations did not virtually affect the cerebral circulation in intact rats. In cerebral ischemia, the cytochrome C preparations increased circulation, showing their more profound effects in case of preadministration of the drugs. The dose-independent effects of HTDP may be associated with the higher transmembranous permeability and the saturation phenomenon of this compound.
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PMID:[The effect of cytochrome c preparations on the cerebral circulation in cerebral ischemia]. 820 42

Hippocampal CA1 neurons are the most vulnerable to transient cerebral ischemia. However, the mechanism has not been fully understood. The level of mRNA for cytochrome C oxidase (COX) subunit I (COX-I), which is encoded by mitochondrial (mt) DNA, progressively decreased in the hippocampal CA1 neurons of gerbils from 3 h of reperfusion after 3.5 min of transient forebrain ischemia and completely disappeared at 7 days. The activity of COX protein also showed an early decrease in CA1 cells and was followed by reduction of the level of COX-I DNA after 2 days. However, succinic dehydrogenase, an mt enzyme encoded by nuclear DNA, maintained normal activity until 1 day in the CA1 cells and significantly decreased at 7 days. The mRNA for mt heat shock protein (HSP) 60 began to increase at 3 h in the CA1 cells and was sustained until 1 day. The mRNAs for 72-kDa heat shock protein and 73-kDa heat shock cognate protein, which are located mainly in the cytoplasm, were induced together in the CA1 cells with a peak at 1-2 days. These results suggest that a disturbance of mt DNA expression occurred in the CA1 neurons at the early stage of reperfusion and was aggravated over the course of time. The disturbance could cause progressive failure of energy production of the cells that eventually results in neuronal cell death.
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PMID:Changes of mitochondrial DNA and heat shock protein gene expressions in gerbil hippocampus after transient forebrain ischemia. 839 36

The purpose of these experiments was to develop a method of isolation, amplification, and identification of cochlear mitochondrial DNA (mtDNA) from minute quantities of tissue. Additionally, studies were designed to detect mtDNA deletions (mtDNA del) from the cochlea that previously have been amplified from other organ systems and tissues. MtDNA del have been associated with many pathologies, including neurological disorders, sensorineural hearing loss, ischemia, cardiomyopathies, and aging. DNA was extracted from rat and human tissues, and polymerase chain reaction was used to amplify mtDNA sequences. A 360 base pair (bp) cytochrome-b gene product and the highly conserved ND1-16S ribosomal ribonucleic acid regions found only in mtDNA were amplified from all tissues. Preliminary studies have identified a 4834 bp mtDNA del in aged rats and a corresponding 4977 bp mtDNA del in aged humans. Additionally, preliminary results in human archival temporal bone studies reveal the presence of the 4977-bp mtDNA deletion in two out of three patients with presbycusis. The deletion was not evident in age-matched control patients without a history of presbycusis. This technique of mtDNA identification makes it possible to investigate specific mtDNA defects from a single cochlea, promoting the study of hereditary hearing loss and presbycusis at a molecular biologic level.
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PMID:Association of mitochondrial DNA deletions and cochlear pathology: a molecular biologic tool. 865 67

A subtraction cDNA library was made using subtractive hybridization of cDNA libraries constructed from gerbil cerebral cortex of control animals and animals 8 hours after a 10-min transient forebrain ischemia. After differential screening, a cDNA clone (named pGSH3) was isolated as a gene that is expressed only after the ischemic insult. The cDNA insert of pGSH3 (0.7 kb) hybridized to the 2.8-kb mRNA of ischemic cerebral cortex. The gene was normally expressed in a small amount in the cerebellum, kidney, and lung, but was not expressed in the cerebral cortex, heart, liver, or jejunum in a detectable amount. Eight hours after the 10-min transient forebrain ischemia, the gene expression became prominent in the cerebral cortex, and the amount of the mRNA also increased in the lung and kidney. An analysis of DNA sequence revealed that the pGSH3 insert has a 91.3% homology with a 72-kd human heat-shock protein (hsp70) gene. These results indicate that an ischemia-induced gene was isolated as a cDNA clone (pGSH3) by subreactive hybridization and differential screening. Expression of the gene was detected in other organs especially in the kidney and lung after transient forebrain ischemia. Hippocampal CA1 neurons are the most vulnerable to transient cerebral ischemia. However, the mechanism has not been fully understood. The level of mRNA for cytochrome C oxidase subunit I (COX-I), which is encoded by mitochondrial DNA (mtDNA), progressively deceased in the hippocampal CA1 neurons of gerbils from 3 hours of the reperfusion after 3.5 min of transient forebrain ischemia, and completely disappeared at 7 days. The activity of cytochrome C oxidase (COX) protein also showed the early decrease in the CA1 cells, and was followed by the reduction of the level of COX-I DNA after 2 days. However, the activity of succinic dehydrogenase (SDH), a mitochondrial enzyme that is encoded by nuclear DNA, maintained normal activity until day 1 in the CA1 cells, and significantly decreased at 7 days. The mRNA for mitochondrial hsp60 began to increase at 3 hours in the CA1 cells, and was sustained until 1 day. The mRNAs for 72-kd (hsp70) and 73-kd (hsc70) heat-shock proteins, which are mainly located in the cytoplasm, were induced together in the CA1 cells with a peak at 1 to 2 days. These results suggest that disturbance of a mitochondrial DNA expression occurred in the CA1 neurons at the early stage of reperfusion, and was aggravated in the course of time. The disturbance could cause progressive failure of energy production of the cells, which eventually results in neuronal cell death.
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PMID:Isolation of an ischemia-induced gene and early disturbance of mitochondrial DNA expression after transient forebrain ischemia. 879 Aug 23

The effect of animal cytochrome C (Ca), biotechnological cytochrome (Cb) and its hemtetradecapeptide (HTDP) on cerebral blood flow autoregulation during rapid decrease of systemic arterial pressure (SAP) was studied in acute experiments on rats. Cytochrome C preparations caused no effect on the autoregulatory responses of the cerebral vessels in animals with normal cerebral circulation. Injection of 5 mg/kg Ca and Cb and 0.8 mg/kg HTDP promoted restoration of the phenomenon of cerebral blood flow autoregulation in ischemic brain damage in change of SAP from 120 to 60 mm Hg. Prophylactic injection of 20 mg/kg Ca and Cb and 3.3 mg/kg HTDP prevented cerebral blood flow autoregulation disturbance caused by transitory brain ischemia.
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PMID:[The effect of cytochrome c preparations on the autoregulation of the cerebral blood flow in ischemia]. 902 1

Edema and cardiovascular dysfunction occur in vertebrates exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during early development. This study examined cytochrome P4501A (CYP1A) induction in endothelium and its possible association with mortality due to the edema and vascular effects of TCDD in lake trout early life stages. Lake trout (Salvelinus namaycush) eggs were injected at 24-50 hr postfertilization with 0.2 microl of 50 mM phosphatidylcholine liposomes or liposomes containing TCDD to give seven doses ranging from 11 to 176 pg TCDD/g egg. Doses of TCDD greater than 44 pg/g egg elicited hemorrhages; yolk sac, pericardial, and meningial edema; craniofacial malformations; regional ischemia; growth retardation; and mortality at the sac fry stage of development. Expression of CYP1A was assessed at four developmental stages, by immunohistochemical analysis of serial sections of individual fish with monoclonal antibody 1-12-3 to teleost CYP1A. CYP1A staining occurred in endothelial cells of many organs of TCDD-exposed but not vehicle-exposed embryos at 1 week prehatch and sac fry at 2 weeks posthatch. Earlier developmental stages examined were negative for CYP1A expression at any dose of TCDD. The strongest response occurred in sac fry at TCDD doses greater than 88 pg TCDD/g egg but was detected at doses as low as 22 pg TCDD/g egg. CYP1A staining in endothelium appeared at lower doses and was stronger than that in other cell types, in both prehatch embryos and posthatch sac fry. Thus, the vascular system is a major initial site affected by TCDD in lake trout early life stages, and the vascular endothelium is a cell type uniquely sensitive to induction of CYP1A in these developing animals. Based on an index of immunohistochemical staining of CYP1A, endothelial CYP1A induction in sac fry by TCDD occurred with an ED50 of 64-69 pg TCDD/g egg, similar to the dose-response for mortality occurring during the sac fry stage of development (LD50 = 47 pg TCDD/g egg). The correlations seen here suggest that CYP1A or aryl hydrocarbon receptor (AhR) in the endothelium may be linked to early lesions that result in TCDD-induced vascular derangements leading to yolk sac, pericardial, and meningial edema that is associated with lake trout sac fry mortality, but the precise mechanism remains to be determined.
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PMID:Correlation of 2,3,7,8-tetrachlorodibenzo-p-dioxin induction of cytochrome P4501A in vascular endothelium with toxicity in early life stages of lake trout. 914 43

The effect of fructose-1, 6-diphosphate (200 mg/kg), cytochrome C (20 mg/kg) and their combinations on the size of the zone of necrosis 4 and 72 h after 15-min transitory myocardial ischemia was studied. Combination of the compounds under study inhibited considerably the development of post-occlusion and reperfusion arrhythmias and reduced the size of necrosis 4 h after their administration as prophylactic and arresting measures (to 23.8 +/- 2.9 and 29.3 +/- 3.6% of the ischemic zone, respectively, in 42.8 +/- 3.8% in the control). A combined course of cytochrome C and fructose diphosphate also limited the size of the necrotic zone 72 h after transitory ischemia. Separate single administration of fructose diphosphate and cytochrome C caused no essential changes in the size of myocardial necrosis recorded 72 h after transitory myocardial ischemia.
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PMID:[The effect of fructose-1,6-diphosphate, cytochrome c and their combination on the size of the necrotic area in transient myocardial ischemia]. 916 79

The aim of the study was to investigate the time course of neutrophil activation after skeletal muscle ischemia in humans and to assess the effect of xanthine oxidase inhibitor allopurinol or cyclooxygenase inhibitor indomethacin. In patients undergoing tourniquet ischemia of the upper limb, polymorphonuclear neutrophils (PMN) were simultaneously isolated from antecubital vein blood of both the contralateral control arm and the tourniquet arm. PMN-superoxide production (PMN-SOP) was determined by a cytochrome C reduction assay, PMN-myeloperoxidase activity (PMN-MPO) by guaiacol oxidation and serum PMN-elastase concentration by an enzyme immunoassay. At 60 min after release of the tourniquet, significant increases of PMN-SOP, PMN-MPO, and serum elastase concentrations were observed in tourniquet arms as compared with control arms (p < .05). Allopurinol (300 mg orally, 12 and 2 h before ischemia) significantly inhibited the increase of PMN-SOP, PMN-MPO, and serum elastase (p < .05). Indomethacin (50 mg orally, 2 h before ischemia) prevented increased PMN-MPO and serum elastase, but prevented increased PMN-SOP only when neutrophils were incubated in the presence of their autologous plasma. These findings suggest that ischemia/reperfusion of human skeletal muscle involves both xanthine oxidase-dependent oxygen free radicals and cyclooxygenase metabolites. These pathways could activate circulating neutrophils which potentially inflict local and remote endothelial injury.
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PMID:Neutrophil activation after skeletal muscle ischemia in humans. 946 69

We have previously demonstrated the generation of reactive oxygen species (ROS) in cultured bovine pulmonary artery endothelial cells (BPAECs) and in isolated perfused rat lungs exposed to high K+ and during global lung ischemia. The present study evaluates the NADPH oxidase pathway as a source of ROS in these models. ROS production, detected by oxidation of the fluorophore, dichlorodihydrofluorescein, increased 2.5-fold in BPAECs and 6-fold in rat or mouse lungs exposed to high (24 mmol/L) K+. ROS generation was markedly inhibited by diphenyliodonium, a flavoprotein inhibitor, and by the synthetic peptide PR-39, an inhibitor of NADPH oxidase assembly, whereas allopurinol had no effect. With ischemia (1 hour), ROS generation by rat and mouse lungs increased 7-fold; PR-39 showed concentration-dependent inhibition of ROS production, with 50% inhibition at 3 micromol/L PR-39. ROS production in lungs exposed to high K+ or ischemia was essentially abolished in mice with a "knockout" of gp91(phox), a membrane-localized cytochrome component of NADPH oxidase; increased ROS production by these lungs after anoxia/reoxygenation was similar to control. PR-39 also inhibited ischemia and the high K+-mediated increase in lung thiobarbituric acid reactive substance. Western blotting of BPAECs and immunocytochemistry of BPAECs and rat and mouse lungs showed the presence of p47phox, a cytoplasmic component of NADPH oxidase and the putative target for PR-39 inhibition. In situ fluorescence imaging in the intact lung demonstrated that the increased dichlorofluorescein fluorescence in these models of ROS generation was localized primarily to the pulmonary endothelium. These studies demonstrate that ROS production in lungs exposed to ischemia or high K+ results from assembly and activation of a membrane-associated NAPDH oxidase of the pulmonary endothelium.
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PMID:Endothelial NADPH oxidase as the source of oxidants in lungs exposed to ischemia or high K+. 975 43


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