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)

The developing cardiovascular system is known to operate normally in a hypoxic environment. However, the functional and ultrastructural recovery of embryonic/fetal hearts subjected to anoxia lasting as long as hypoxia/ischemia performed in adult animal models remains to be investigated. Isolated spontaneously beating hearts from Hamburger-Hamilton developmental stages 14 (14HH), 20HH, 24HH, and 27HH chick embryos were subjected in vitro to 30 or 60 min of anoxia followed by 60 min of reoxygenation. Morphological alterations and apoptosis were assessed histologically and by transmission electron microscopy. Anoxia provoked an initial tachycardia followed by bradycardia leading to complete cardiac arrest, except for in the youngest heart, which kept beating. Complete atrioventricular block appeared after 9.4 +/- 1.1, 1.7 +/- 0.2, and 1.6 +/- 0.3 min at stages 20HH, 24HH, and 27HH, respectively. At reoxygenation, sinoatrial activity resumed first in the form of irregular bursts, and one-to-one atrioventricular conduction resumed after 8, 17, and 35 min at stages 20HH, 24HH, and 27HH, respectively. Ventricular shortening recovered within 30 min except at stage 27HH. After 60 min of anoxia, stage 27HH hearts did not retrieve their baseline activity. Whatever the stage and anoxia duration, nuclear and mitochondrial swelling observed at the end of anoxia were reversible with no apoptosis. Thus the embryonic heart is able to fully recover from anoxia/reoxygenation although its anoxic tolerance declines with age. Changes in cellular homeostatic mechanisms rather than in energy metabolism may account for these developmental variations.
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PMID:Developmental changes in cardiac recovery from anoxia-reoxygenation. 1212 51

Pituitary adenylate cyclase activating polypeptide (PACAP) has neurotrophic and neuroprotective effects against various cytotoxic agents in vitro, and ischemia in vivo. Anoxia tolerance is most highly developed in some species of turtles. Recently, we have demonstrated high levels of PACAP38 in the turtle brain, exceeding those in corresponding rat and human brain areas by 10- to 100-fold. The aim of the present study was to investigate with electrophysiological methods the protective effects of PACAP in anoxia-induced neuronal damage of turtle retinal horizontal cells. Adult turtles (Pseudemys scripta elegans) were used for the experiments. After decapitation, half of the isolated eyecup slices were placed into a non-oxygenated Ringer solution, the other half into 0.165 microM PACAP solution. Intracellular recordings were obtained from horizontal cells 18, 22, 42 and 46 h after removal of the eyes. The amplitudes of light responses with the exception of the 0-h measurement, were larger at all time-points in PACAP-incubated slices than in control retinal slices. After both 18 and 22 h, the response amplitudes of PACAP-treated cells exceeded those taken from control horizontal cells by 1.2-fold. At later times, this difference became larger than 2-fold. In summary, the present results provide evidence that PACAP has neuroprotective effects on the anoxic retinal cells in the turtle.
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PMID:PACAP inhibits anoxia-induced changes in physiological responses in horizontal cells in the turtle retina. 1240 17

Congenital suprabulbar palsy is clinically characterized by problems of feeding, swallowing, drooling, and dysarthria. Epilepsy, delayed motor, cognitive, and language development, as well as learning disabilities may co-exist. Aetiology of the syndrome is diverse, yet studies often attribute it to specific entities. We report on nine patients (seven males, two females; age range 2 to 20 years), highlighting the heterogeneous causes of suprabulbar palsy using neuroimaging and emphasizing the need for systematic investigation for early detection and management. We identified patients with symmetrical infarcts involving the perisylvian region, apart from already-recognized conditions, such as congenital bilateral perisylvian syndrome (CBPS; a neuronal migration disorder) and Worster-Drought syndrome. CBPS simulates Foix-Chavany-Marie syndrome in adults because of staged stroke but differs in many respects. Anoxia or ischemia to the developing brain could be a common plausible aetiology. Studies with large groups of patients are required to differentiate the various subgroups and identify essential criteria for diagnosis.
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PMID:Congenital suprabulbar palsy: a distinct clinical syndrome of heterogeneous aetiology. 1534 22

Activation of Na(+)/H(+) exchange (NHE) plays a major role in cell death following ischemia/hypoxia in many cell types, yet counteracts apoptotic cell death after other stimuli. To address the role of NHE activity in regulation of cell death/survival, we examined the causal relationship between NHE, p38 mitogen-activated protein kinase (MAPK), ERK1/2, p53, and Akt activity, and cell death, after chemical anoxia in NIH3T3 fibroblasts. The NHE1 inhibitor 5'-(N-ethyl-N-isopropyl) amiloride (EIPA) (5 muM), as well as removal of extracellular Na(+) [replaced by N-methyl-D: -glucamine (NMDG(+))], prevented recovery of intracellular pH (pH(i)) during chemical anoxia (10 mM NaN(3) +/- 10 mM glucose), indicating that activation of NHE was the dominating mechanism of pH(i) regulation under these conditions. NHE activation by chemical anoxia was unaffected by inhibitors of p38 MAPK (SB203580) and extracellular signal-regulated kinase (ERK) (PD98059). In contrast, chemical anoxia activated p38 MAPK in an NHE-dependent manner, while ERK1/2 activity was unaffected. Anoxia-induced cell death was caspase-3-independent, mildly attenuated by EIPA, potently exacerbated by SB203580, and unaffected by PD98059. Ser(15) phosphorylation of p53 was increased by anoxia in an NHE- and p38 MAPK-independent manner, while Akt activity was unaffected. It is suggested that after chemical anoxia in NIH3T3 fibroblasts, NHE activity is required for activation of p38 MAPK, which in turn protects the cells against anoxia-induced death. In spite of this, NHE inhibition slightly attenuates anoxia-induced cell death, likely due to the involvement of NHE in other anoxia-induced death pathways.
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PMID:Roles of Na+/H+ exchange in regulation of p38 mitogen-activated protein kinase activity and cell death after chemical anoxia in NIH3T3 fibroblasts. 1733 79

Sensory neurons can detect ischemia and transmit pain from various organs. Whereas the primary stimulus in ischemia is assumed to be acidosis, little is known about how the inevitable metabolic challenge influences neuron function. In this study we have investigated the effects of anoxia, aglycemia, and acidosis upon intracellular Mg(2+) concentration [Mg(2+)](i) and intracellular pH (pH(i)) in isolated sensory neurons. Anoxia, anoxic aglycemia, and acidosis all caused a rise in [Mg(2+)](i) and a fall in pH(i). The rise in [Mg(2+)](i) in response to acidosis appears to be due to H(+) competing for intracellular Mg(2+) binding sites. The effects of anoxia and aglycemia were mimicked by metabolic inhibition and, in a dorsal root ganglia (DRG)-derived cell line, the rise in [Mg(2+)](i) during metabolic blockade was closely correlated with fall in intracellular ATP concentration ([ATP](i)). Increase in [Mg(2+)](i) during anoxia and aglycemia were therefore assumed to be due to MgATP hydrolysis. Even brief periods of anoxia (<3 min) resulted in rapid internal acidosis and a rise in [Mg(2+)](i) equivalent to a decline in MgATP levels of 15-20%. With more prolonged anoxia (20 min) MgATP depletion is estimated to be around 40%. With anoxic aglycemia, the [Mg(2+)](i) rise occurs in two phases: the first beginning almost immediately and the second after an 8- to 10-min delay. Within 20 min of anoxic aglycemia [Mg(2+)](i) was comparable to that observed following complete metabolic inhibition (dinitrophenol + 2-deoxyglucose, DNP + 2-DOG) indicating a near total loss of MgATP. The consequences of these events therefore need to be considered in the context of sensory neuron function in ischemia.
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PMID:Effects of anoxia, aglycemia, and acidosis on cytosolic Mg2+, ATP, and pH in rat sensory neurons. 1797 42

The deleterious effects of anoxia followed by reperfusion with oxygen in higher animals including mammals are well known. A convenient and genetically well characterized small-animal model that exhibits reproducible, quantifiable oxygen reperfusion damage is currently lacking. Here we describe the dynamics of whole-organism metabolic recovery from anoxia in an insect, Drosophila melanogaster, and report that damage caused by oxygen reperfusion can be quantified in a novel but straightforward way. We monitored CO(2) emission (an index of mitochondrial activity) and water vapor output (an index of neuromuscular control of the spiracles, which are valves between the outside air and the insect's tracheal system) during entry into, and recovery from, rapid-onset anoxia exposure with durations ranging from 7.5 to 120 minutes. Anoxia caused a brief peak of CO(2) output followed by knock-out. Mitochondrial respiration ceased and the spiracle constrictor muscles relaxed, but then re-contracted, presumably powered by anaerobic processes. Reperfusion to sustained normoxia caused a bimodal re-activation of mitochondrial respiration, and in the case of the spiracle constrictor muscles, slow inactivation followed by re-activation. After long anoxia durations, both the bimodality of mitochondrial reactivation and the recovery of spiracular control were impaired. Repeated reperfusion followed by episodes of anoxia depressed mitochondrial respiratory flux rates and damaged the integrity of the spiracular control system in a dose-dependent fashion. This is the first time that physiological evidence of oxygen reperfusion damage has been described in an insect or any invertebrate. We suggest that some of the traditional approaches of insect respiratory biology, such as quantifying respiratory water loss, may facilitate using D. melanogaster as a convenient, well-characterized experimental model for studying the underlying biology and mechanisms of ischemia and reperfusion damage and its possible mitigation.
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PMID:Oxygen reperfusion damage in an insect. 1806 61

Nociceptive neurons play an important role in ischemia by sensing and transmitting information to the CNS and by secreting peptides and nitric oxide, which can have local effects. While these responses are probably primarily mediated by acid sensing channels, other events occurring in ischemia may also influence neuron function. In this study, we have investigated the effects of anoxia and anoxic aglycemia on Ca2+ regulation in sensory neurons from rat dorsal root ganglia. Anoxia increased [Ca2+]i by evoking Ca2+ release from two distinct internal stores one sensitive to carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) and one sensitive to caffeine, cyclopiazonic acid (CPA), and ryanodine [assumed to be the endoplasmic reticulum (ER)]. Anoxia also promoted progressive decline in ER Ca2+ content. Despite partially depolarizing mitochondria, anoxia had relatively little effect on mitochondrial Ca2+ uptake when neurons were depolarized but substantially delayed mitochondrial Ca2+ release and subsequent Ca2+ clearance from the cytosol on repolarization. Anoxia also reduced both sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) activity and Ca2+ extrusion [probably via plasma membrane Ca2+-ATPase (PMCA)]. Thus anoxia has multiple effects on [Ca2+]i homeostasis in sensory neurons involving internal stores, mitochondrial buffering, and Ca2+ pumps. Under conditions of anoxic aglycemia, there was a biphasic and more profound elevation of [Ca2+]i, which was associated with complete ER Ca2+ store emptying and progressive, and eventually complete, inhibition of Ca2+ clearance by PMCA and SERCA. These data clearly show that loss of oxygen, and exhaustion of glycolytic substrates, can profoundly affect many aspects of cell Ca2+ regulation, and this may play an important role in modulating neuronal responses to ischemia.
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PMID:Effects of anoxia and aglycemia on cytosolic calcium regulation in rat sensory neurons. 1841 27

Although differentiated and undifferentiated cells can be exposed to ischemic conditions in cases of injury or inflammation, the effects of ischemia on cell survival and differentiation have not been well characterized. Here, we characterize the response of porcine dental pulp-derived cells (pDPCs) to culture conditions that approximate ischemia. Dental pulp is often exposed to ischemia due to narrow vascular openings in the tooth, which may affect the differentiation status of pDPCs. In this study, we investigated the influence of various ischemic conditions on differentiation-induced and non-induced pDPCs. To understand the character of cells used in this study, reported cell surface markers for dental pulp stem cells were investigated. pDPCs were CD90(low), CD105(+), and alpha-smooth muscle actin positive and showed osteogenic/chondrogenic differentiation potential. Anoxia was the most detrimental factor to cell viability, whereas hypoxia did not significantly affect survival. Glucose concentrations had a significant, mechanism-dependent effect on cell death. The presence of glucose correlated with caspase-dependent cell death, whereas the absence of glucose was linked to caspase-independent cell death. In contrast, differentiation status (i.e., induced versus non-induced pDPCs) did not affect the degree or mechanism of cell death. Finding depletion of specific markers by reverse transcription-polymerase chain reaction in both induced and non-induced cells suggests that the cells are de-differentiating under anoxia. Non-induced pDPCs were susceptible to anoxic induction of Oct-4, Sox-2, and hypoxia inducible factor-2alpha, while these genes did not change in induced pDPCs. Re-differentiation analysis revealed that the surviving cells from non-induced pDPCs showed twofold higher alkaline phosphatase activity as compared with induced pDPCs, which suggest greater plasticity among the surviving fraction of non-induced pDPCs. These data showed that the ischemic conditions have similar detrimental influence on both undifferentiated and differentiated pDPCs, and affect differentiation status of pDPCs. Furthermore, ischemic conditions may influence the plasticity of undifferentiated pDPCs.
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PMID:Effect of ischemic culture conditions on the survival and differentiation of porcine dental pulp-derived cells. 1856 3

Cerebral anoxia-ischemia (CAI) is a potent inhibitor of cerebral hyperactivity and a potential mechanism of seizure self-termination. Prolonged ictal asystole (IA) invariably leads to CAI and has been implicated as a potential cause of sudden unexplained death in epilepsy (SUDEP). IA was seen in eight consecutive patients (0.12% of all patients monitored). Ten of their seizures with IA had evidence of CAI on electroencephalography (EEG), manifested by bilateral hypersynchronous slowing (BHS), and were compared to 18 seizures without signs of CAI. The ictal EEG pattern resolved in all 10 CAI events with onset of the BHS. The period from IA onset to seizure end was reduced in events with BHS compared to events without BHS (10.5 s vs. 28.3 s, respectively; p = 0.005), and the total seizure duration tended to be shorter. Anoxia-ischemia as a result of IA may represent an effective endogenous mechanism for seizure termination and may explain why the hearts of patients with ictal asystole reported to date in the literature resumed beating spontaneously.
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PMID:Anoxia-ischemia: a mechanism of seizure termination in ictal asystole. 1949 47

The responsiveness of the smallest blood vessels of the human skin was measured in systemic anoxemia, hypercapnia, acidosis, and alkalosis. A method was used which measured quantitatively the reactive hyperemia produced by a standardized period of local ischemia of these fine vessels. By timing the clearing period of the threshold hyperemia response a direct indication of blood flow in these fine vessels was obtained. The following conclusions were reached concerning the responses of the smallest blood vessels of the skin. 1. Systemic anoxemia causes a decrease in sensitivity to local ischemia and a slowing of the blood flow. 2. Hypercapnia prevents the changes resulting from anoxemia. 3. These changes in the smallest blood vessels of the skin occur independently of changes in pulse rate, blood pressure, and respiratory rate and depth. 4. With systemic acidosis there is a decrease in sensitivity to local ischemia and a slowing of blood flow. The exact opposite takes place in systemic alkalosis. 5. The view is advanced, after due consideration of the facts, that the carbon dioxide concentration of the blood, or something directly associated with it, is the most important factor determining the sensitivity of these vessels, rather than oxygen saturation or changes in blood pH.
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PMID:QUANTITATIVE ALTERATIONS IN THE HYPEREMIA RESPONSES TO LOCAL ISCHEMIA OF THE SMALLEST BLOOD VESSELS OF THE HUMAN SKIN FOLLOWING SYSTEMIC ANOXEMIA, HYPERCAPNIA, ACIDOSIS, AND ALKALOSIS. 1987 Dec 46


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