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

The human heart in the fasting state extracts free fatty acids (FFA), glucose, lactate, pyruvate, and ketones from circulating blood. The utilization of FFA accounts for most of the oxygen consumed and energy produced at rest. Patients with angiographically demonstrable coronary artery disease and stable angina pectoris have a resting myocardial metabolism similar to that of normal individuals. During atrial pacing in normal persons, there is a significant enhancement of glucose uptake but that of FFA is unchanged, and the oxidation of carbohydrates accounts for more than 60% of the energy produced. In patients with stable angina, myocardial perfusion becomes regionally inadequate during stress. Despite the increase of myocardial glucose utilization, carbohydrate oxidation is negligible. Pyruvate will not be oxidized but in the presence of increased amounts of reduced coenzymes will be reduced to lactate. In addition, a greater amount of alanine will be released by the myocardium through the transamination of pyruvate, with a concomitantly greater uptake of glutamate that serves as the NH2 donor. In addition, glutamate may be used as an anaerobic fuel through conversion to succinate coupled with GTP formation. Although coronary hemodynamics, including myocardial perfusion, return to baseline within a few minutes after stress, a longer time course is needed for myocardial metabolism to become normal. In particular, myocardial utilization of exogenous glucose remains higher well after the normalization of hemodynamic parameters. This is more pronounced in postischemic myocardium, but it also occurs in nonischemic muscle, and glucose is presumably used for rebuilding glycogen stores that were depleted during ischemia.
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PMID:Metabolic markers of stress-induced myocardial ischemia. 202 52

Incomplete ischemia of the spinal cord of rabbits was produced by a 40-min occlusion of the abdominal aorta followed by 1 and 4 days of recirculation. Regional evaluation of ATP-induced bioluminescence after 20 min of ischemia revealed ATP depletion mainly in the gray matter of the spinal cord. After 40 min of ischemia, ATP-induced bioluminescence was too faint to expose the photographic film. Within 1 and 4 days of recovery following 40 min of ischemia, restitution of ATP was regionally heterogeneous, reduced predominantly in the anterior horns of gray matter. Polysome profiles remained unaltered during the ischemic period, but a marked disaggregation of polyribosomes occurred after 10 min of recirculation. Protein synthesis in a cell-free system was inhibited by the addition of a postischemic cytosol or protein fraction isolated from cytosols on a DEAE column. The inhibition can be overcome by the addition of each initiation factor 2 (eIF-2), GTP and GDP exchange factor (GEF). Occlusion of abdominal aorta for 40 min results in decrease in monoamine oxidase accumulation in both proximal and distal ligature placed on sciatic nerve. Within 4 days of recovery the transport was progressively depressed to 22 and 21% in the proximal and distal direction, respectively.
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PMID:Molecular mechanisms of ischemic damage of spinal cord. 244 28

Regulation of cardiac beta-adrenergic receptors during hypoxia and ischemia is an area of active investigation, with some investigators reporting an increase in sarcolemmal beta-receptor number after ischemia. Previous studies have been limited by the necessity of examining beta-adrenergic receptor properties in membrane preparations from hypoxic or ischemic cardiac tissue and drawing conclusions about receptor localization in intact tissue from the behavior of a fraction of total receptors in membrane populations. As an approach to examining beta-receptor properties under well-defined pathophysiological conditions in intact heart cells, we studied cell-surface beta-receptors and adenylate cyclase activity in intact cultured chick embryo ventricular cells under conditions of controlled hypoxia and reoxygenation. During 2 h of hypoxia (PO2 less than 1.5 Torr) there was a progressive decline in cell surface beta-receptors from 26 +/- 2 to 10 +/- 6 fmol/mg (P less than 0.003) with no change in antagonist or agonist affinity. Receptor number recovered fully during 2 h of reoxygenation. Basal adenosine 3',5'-cyclic monophosphate (cAMP) production was unchanged, but response to isoproterenol in the absence or presence of a phosphodiesterase inhibitor decreased to about half of the response for normoxic cells but fully recovered during reoxygenation in a pattern similar to that for receptor number. Although [ATP] declined significantly during hypoxia (from 35 to 25 nmol/mg), the decline in [GTP] was marginal (4.3 to 3.9 nmol/mg), making it unlikely that substrate for guanine nucleotide regulatory protein was limiting for beta-adrenergic signal transduction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-adrenergic receptor regulation during hypoxia in intact cultured heart cells. 253 45

The effect of 1 hour of myocardial ischemia on the function of the stimulatory guanine-nucleotide-binding protein Gs was examined. This study follows our recent finding that myocardial ischemia increases the density of beta-adrenoreceptors in a conscious canine model while having the opposite effect on the activity of adenylate cyclase. Coronary artery occlusion was induced in five conscious dogs and verified by measurement of blood flow using the Doppler and microsphere techniques. Alterations in the level and function of Gs were examined in sarcolemmal membranes prepared from ischemic and nonischemic regions of the left ventricle. After 1 hour of coronary artery occlusion, the functional activity of sarcolemmal Gs, as determined by reconstitution with cyc- membranes, decreased by 27 +/- 7% in the ischemic zone. Cholera toxin labeling performed in parallel with the reconstitution studies demonstrated a similar decrease of 28 +/- 7%. This was associated with decreases in basal activity and decreases in adenylate cyclase activity stimulated by GTP, GTP plus isoproterenol, sodium fluoride, and forskolin. Thus, a defect distal to the beta-adrenoreceptor occurs in the transduction of adrenergic signals to the heart as a consequence of 1 hour of ischemia.
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PMID:One hour of myocardial ischemia decreases the activity of the stimulatory guanine-nucleotide regulatory protein Gs. 255 29

Oxidative loading during the reperfusion of the proximal jejunum of rats following a one hour-period of complete ischemia was demonstrated in in vivo-experiments by the increases of the GSSG: total glutathione ratio and the concentration of TBA-RS. The pretreatment of the animals with the xanthine oxidoreductase inhibitor allopurinol diminished the accumulation of GSSG and of TBA-RS. It was concluded that the purine nucleotide degradation is an important source of oxygen reduction products in reoxygenated small intestine. The tissue concentrations of nucleotides, nucleosides and nucleobases were measured by an ion-pair reversed-phase HPLC separation. There occurred fast declines of ATP and GTP concentrations during ischaemia leading to temporary increases of nucleoside mono- and diphosphate pools. The hypoxanthine concentration is increased about twentyfold during oxygen deficiency. The ATP and GTP restoration during the reperfusion was accelerated in presence of allopurinol. The shares of the beneficial allopurinol effects are not yet clarified.
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PMID:Radical formation in the rat small intestine during and following ischemia. 258 51

Peroxidative loading during the reoxygenation of the rat small intestine following a complete ischemia was demonstrated in in vivo-experiments by the increases of the glutathione disulphide (GSSG): total glutathione ratio and the concentration of thiobarbituric acid-reactive substances (TBA-RS). The pretreatment of the rats with allopurinol diminished the accumulation of GSSG and of TBA-RS. From these effects was concluded that the purine nucleotide degradation is an important source of oxygen reduction products leading to peroxidations. The concentrations of nucleotides, nucleosides and nucleobases were measured by an ion-pair reversed-phase HPLC. The restoration of ATP and GTP concentrations during the reoxygenation period was accelerated by the application of allopurinol.
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PMID:Nucleotide degradation and radical formation in ischemic and reperfused small intestine. 273 Jun 3

A therapeutic role for naloxone during stroke has been suggested, but a neurochemical site of action remains to be determined. Previous work with the gerbil cerebral cortex has shown that either bilateral secondary ischemia (60-min occlusion of the carotid arteries followed by 40-min reflow) or unilateral primary ischemia (permanent ligation of one carotid artery for 6 hr in symptomatic animals) produced deficits in both Na+, K+-ATPase (EC 3.6.1.3) activity and various parameters of activation of adenylate cyclase (EC 4.6.1.1). Pretreatment of gerbils with either naloxone or morphine failed to ameliorate or exacerbate, respectively, the neurological signs of ischemia; however, morphine did reduce mortality. Infusion of naloxone prior to ischemia afforded varying degrees of protection to forskolin, GTP analogs, and NE (norepinephrine) activation of adenylate cyclase, as well as to Na+, K+-ATPase (bilateral ischemia only). Similarly, morphine inhibited damage to basal activity of adenylate cyclase and to stimulation by NE, forskolin, and Gpp (NH)p (5'-guanylyl imidodiphosphate). Under in vitro conditions morphine increased the basal activity of adenylate cyclase but reduced responses to NE and forskolin. Furthermore, morphine injected into control gerbils elevated basal- and forskolin-elicited activities but reduced the activation of adenylate cyclase by NE.
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PMID:Effects of naloxone and morphine on cerebral ischemia in gerbils. 294 23

We evaluated the effects of ischemic injury on the myocardial adenylate cyclase system, 5 h after ligation of the left anterior descending coronary in 5 anesthetized dogs. Crude cardiac membrane preparations were isolated from control and ischemic areas of ventricular myocardium and tested for: 1. L-(125I)iodocyanopindolol binding, in the absence and presence of +/- -isoprenaline and GTP, and 2. adenylate cyclase activity. The density of beta-adrenoceptors increased by 35% in membranes from ischemic areas while the proportion of receptors in a high affinity state for +/- -isoprenaline decreased from 43% to 20%. Adenylate cyclase activities in the basal state and under stimulation with NaF, forskolin, Gpp(NH)p, +/- -isoprenaline and VIP were all markedly and similarly reduced, being only about 30% of comparable activities in membranes from control areas. The +/- -isoprenaline subsensitivity of cardiac adenylate cyclase can, thus, be attributed to a defective enzymatic system and not to a reduction in the number of beta-adrenoceptors implying that the internal components of the system were more sensitive to acute ischemia than the outward oriented hormone receptors. It is tempting to ascribe this uncoupling to a functional depletion in the guanine nucleotide-binding regulatory protein Ns that might reflect a loss of high energy phosphate stores including GTP.
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PMID:Uncoupling between beta-adrenoceptors and adenylate cyclase in dog ischemic myocardium. 299 17

A variety of pharmacological agents were used as experimental probes to determine with greater precision the site(s) of damage to cerebral adenylate cyclase as a consequence of postischemic reperfusion in the gerbil. A paradigm of 60-min bilateral ischemia followed by 40-min reperfusion results in a decreased sensitivity of the catalytic site of adenylate cyclase to Mn2+. Likewise, the GTP-transducer site (guanine nucleotide regulatory or G protein) revealed depressed responses to GTP in the absence or presence of norepinephrine, dopamine agonists, substance P, yohimbine, and cholera and pertussis toxins. Moreover, a crude preparation of GTPase disclosed that damage elicited by postischemic reperfusion was directed to the higher-affinity form of this enzyme, which is associated with the overall function of the guanine nucleotide regulatory protein. Injury to adenylate cyclase was unrelated either to the ability of adrenergic ligands to bind to associated receptor sites or to the capacity of the brain to generate visual evoked potentials in response to visual stimuli.
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PMID:Further probes into the molecular sites of damage to cerebral adenylate cyclase following postischemic reperfusion. 310 40

Nucleotide metabolism was studied in rats during and following the induction of 10 min of forebrain ischemia (four-vessel occlusion model). Purine and pyrimidine nucleotides, nucleotides, and bases in forebrain extracts were quantitated by HPLC with an ultraviolet detector. Ischemia resulted in a severe reduction in the concentration of nucleoside triphosphates (ATP, GTP, UTP, and CTP) and an increase in the concentration of AMP, IMP, adenosine, inosine, hypoxanthine, and guanosine. During the recovery period, both the phosphocreatine level and adenylate energy charge were rapidly and completely restored to the normal range. ATP was only 78% of the control value at 180 min after ischemic reperfusion. Levels of nucleosides and bases were elevated during ischemia but decreased to values close to those of control animals following recirculation. Both the decrease in the adenine nucleotide pool and the incomplete ATP recovery were caused by insufficient reutilization of hypoxanthine via the purine salvage system. The content of cyclic AMP, which transiently accumulated during the early recirculation period, returned to the control level, paralleling the decrease of adenosine concentration, which suggested that adenylate cyclase activity during reperfusion is modulated by adenosine A2 receptors. The recovery of CTP was slow but greater than that of ATP, GTP, and UTP. The GTP/GDP ratio was higher than that of the control animals following recirculation.
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PMID:Mononucleotide metabolism in the rat brain after transient ischemia. 370 29


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