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

Organ perfusion methods offer a number of advantages in biologic studies but require full characterization before application. Two new methods for perfusing rat testes were characterized and compared with recirculating hemicorpus system. These preparations, selective and isolated testicular perfusion, are nonrecirculating and consequently, allow direct measurement of testosterone secretion. In both systems, testosterone production was a fuction of the dose of human chorionic gonadotropin in the perfusion medium up to 1000 mIU per ml which appeared to be inhibitory. The isolated testis method, in comparison with the selective, is more sensitive to human chorionic gonadotropin, requires less perfusion medium, maintains normal blood flow rates and water content, and is associated with no ischemia at commencement of perfusion. However, this system does not retain normal levels of ATP and GTP after 3 hr of perfusion. Whereas both procedures may be used for studies of testosterone secretion and androgen receptors, the inability to maintain testicular ATP and GTP levels indicates that present methods are not suitable for study of processes dependent upon high energy phosphate metabolism.
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PMID:Evaluation of methods for perfusing rat testes. 90 14

The effect of ischemia on synthesis of myocardial proteins was investigated using a model of perfusion in which low levels of coronary flow were provided to paced hearts worked against a closed aortic outflow tract. These conditions rapidly produced ischemia and ventricular failure, as evidence by reduced coronary flow, increased left atrial pressure, and decreased pressure development. Protein synthesis was inhibited in a subsequent 1-hour period, during which a minimal coronary flow was maintained by retrograde perfusion. ATP, GTP, and creatinine phosphate were depleted in ischemic hearts and AMP accumulated. Production and accumulation of lactate within the tissue increased, whereas palmitate uptake was inhibited. The inhibition of protein synthesis was not associated with reduced levels of intracellular amino acids. During ischemia, decreased levels of ribosomal subunits as compared to paced or unpaced aerobic hearts suggested that peptide chain elongation was slow relative to initiation. Provision of insulin further reduced subunit levels but did not increase protein synthesis, suggesting that the hormone did not prevent inhibition of peptide chain elongation in energy-poor hearts.
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PMID:Effects of anoxia and ischemia on protein synthesis in perfused rat hearts. 126 87

We studied the mechanisms underlying the increase in automaticity induced by alpha 1-adrenergic stimulation of normal and "ischemic" canine Purkinje fibers. Fibers were superfused with a control Tyrode's solution, followed by an ischemic superfusate that included 10 mM KCl, 5 mM NaHCO3, Po2 of 10-25 mm Hg, and pH 6.7. To exclude beta-adrenergic actions, propranolol was added to all solutions. In the presence of phenylephrine, normal automaticity at high membrane potentials usually decreased, whereas the incidence of abnormal automaticity during ischemia was increased from a control value of 10% to 30%. Block of an alpha 1-receptor subtype with chloroethylclonidine in the presence of phenylephrine caused normal automaticity to increase in all fibers studied and significantly increased abnormal automaticity to 70%. The alpha-adrenergic-induced increase in automaticity did not occur in ischemic fibers from animals pretreated with pertussis toxin (PTX), which ADP-ribosylated and functionally inactivated the 41-kd family of GTP regulatory proteins. In contrast, the use of PTX enhanced the increase in automaticity induced by phenylephrine in normally polarized Purkinje fibers. Ryanodine, which blocks sarcoplasmic reticulum Ca2+ release, attenuated the increase in normal automaticity in nonischemic fibers but had no effect on abnormal automaticity in ischemic fibers. The increase in abnormal automaticity was, however, blocked by the alpha 1 subtype blocker WB 4101, which also blocks the increase in automaticity in normal fibers. In conclusion, the increase in abnormal automaticity in ischemic Purkinje fibers depends on a WB 4101-sensitive alpha 1-adrenergic receptor subtype whose actions are transduced by a PTX-sensitive 41-kd G protein and are not blocked by ryanodine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Positive chronotropic responses induced by alpha 1-adrenergic stimulation of normal and "ischemic" Purkinje fibers have different receptor-effector coupling mechanisms. 132 30

The brain cyclic AMP generation was studied in rats subjected to 15 min of cardiac arrest. We have used a particulate, synaptoneurosomal fraction to demonstrate the effect of ischemia in vivo on the responsiveness of adenylate cyclase (AC) system. It has been shown that, although there is a slight decrease in AC activity after ischemia, the in vitro fractions produce more cAMP in response to a variety of stimuli, suggesting an indirect, nonadenylate cyclase activation mechanism. For elucidation of this mechanism we have probed phorbol-12,13-dibutyrate (PDBu) as a direct PKC activator, forskolin to activate the catalytic subunit of AC, and cholera toxin (CT) for stabilizing the active, GTP-bound form of stimulatory guanine nucleotide binding protein (Gs). All these postreceptor AC modulators as well as the receptor activators such as adenosine and alpha 1-adrenergic agonists markedly enhanced cAMP production in the rat brain particulate fraction, although the postischemic hyperactive response to these stimuli was still present. However, when AC was stimulated by the combination of CT and PDBu, cAMP responses were identical in both control and postischemic fractions. The data, taken together, support the hypothesis that ischemia increases cAMP accumulation by facilitating the postreceptor AC activation through a PKC-involving pathway and by promoting the stronger coupling of membrane AC receptors with G-protein. Protein kinase C (PKC) activity during cerebral ischemia was also investigated. In contradistinction to our expectation PKC decreased significantly in the ischemic brain to 85% of the control activity in the cytosol and 72% in the membranes. However, in the incubated post-ischemic brain particulate fraction a relative increase in the membrane-bound form of the enzyme, from 30% for control to 53% for ischemia, was observed. This may suggest that ischemia-induced membrane changes could promote the enzyme translocation/activation during recovery, resulting in the sensitization of cAMP producing system.
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PMID:Postreceptor modulation of cAMP accumulation in rat brain particulate fraction after ischemia--involvement of protein kinase C. 135 40

Slice preparations were made from the hippocampus of gerbils after 5 min of ischemia by carotid artery occlusion and the membrane properties of pyramidal neurons were examined. A majority of CA1 neurons lost the capacity for long-term potentiation following tetanic stimulation of the input fibers. CA3 pyramidal neurons, in contrast, preserved responses similar to those in the normal gerbil. Following ischemia, CA1 pyramidal neurons showed increased spontaneous firing that was highly voltage dependent and was blocked by intracellular injection of the Ca2+ chelator, EGTA. Thirty-five percent of CA1 neurons showed an abnormal slow oscillation of the membrane potential after 24 h following ischemia. Intracellular injection of GTP gamma S or IP3 produced facilitation of the oscillations followed by irreversible depolarization. Our results indicate that ischemia-damaged CA1 neurons suffer from abnormal Ca2+ homeostasis, involving IP3-induced liberation of Ca2+ from internal stores.
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PMID:Disturbance of membrane function preceding ischemic delayed neuronal death in the gerbil hippocampus. 156 36

Cerebral ischemia produces perturbation of signal transduction systems in neurons. In order to estimate the contribution of guanine nucleotide-binding protein (G-protein) to hippocampal neuronal death, the effect of pertussis toxin (PTX) on the CA1 pyramidal cell damage after transient forebrain ischemia in rats was examined. PTX was administered 3 days before 20 min of transient forebrain ischemia. PTX injection into the CA1 subfield failed to alter the number of ischemic-damaged CA1 pyramidal cells. In contrast, ventricular PTX injection exacerbated CA1 pyramidal cell damage. We also studied postischemic alteration of GTP binding sites in the hippocampal formation using quantitative in vitro autoradiography. Autoradiographic imaging demonstrated predominant distribution of GTP binding sites in synaptic areas in the hippocampus. No significant change of GTP binding activity was observed in the hippocampus until 2 days after recirculation. Seven days after ischemia, when the CA1 pyramidal cells were depleted, the GTP binding sites of the strata oriens and radiatum in the CA1 subfield had reduced by 32% and 31%, respectively. In contrast, GTP binding in the CA3 subfield and the dentate gyrus remained unaltered throughout the reperfusion period. These results suggest that the amount of G-proteins as estimated by GTP binding remained unaltered in the hippocampus during the early recirculation period, when the CA1 pyramidal cells were morphologically intact, and that signal transduction pathways mediated by Gi and Go do not play a major role in delayed death of the CA1 pyramidal cells.
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PMID:The role of GTP binding proteins in ischemic brain damage: autoradiographic and histopathological study. 161 6

We have used brain (dog, rat) and spinal cord (dog, rabbit) cell-free systems to study early postischaemic inhibition of protein synthesis. Ischaemia alone produced a relatively small decrease in activity of all subcellular systems used. When 15 min of normoxic reperfusion was used, more than 30% decrease (p less than 0.01) in [14C]-leucine incorporation was detected. A translational inhibitor that appeared in the postribosomal supernatant fraction at the early stage of reperfusion reduced translational capacity of an initiating cell-free system. It also phosphorylated the small (38 kDa) subunit of eukaryotic initiation factor 2 (eIF-2) in vitro. Effect of the inhibitor can be reversed by addition of partially purified intact eIF-2 and/or high concentration (2 mmol/l) of GTP. A prevention of postischaemic free oxygen radical formation by the reoxygenation with hypoxaemic blood, containing 37.5 mm Hg O2 at 0-5 min and 56 mm Hg O2 at 6-10 min of recirculation, that was followed by 5 min of normoxic reperfusion, resulted in a significant increase (p less than 0.02) of polypeptide chain synthesis in vitro when compared with normoxic reperfusion.
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PMID:Mechanism of protein synthesis inhibition in CNS during postischaemic reperfusion. 181 18

The observability of nucleoside triphosphate (NTP) by 31P NMR spectroscopy was studied in the isolated rat liver during hypothermic perfusion and a subsequent 4-h cold ischemia. The influence of hypothermia (4 degrees C) was examined because of its delaying effects on cell injury induced by the ischemic conditions. The viability of the liver after hypothermic ischemia was assessed by measuring the recovery of the beta-NTP resonance after reperfusion. In 4-h cold ischemic liver, recovery was found to be in the range of 90-100% and consequently NTP visibility was studied under these conditions. Because the individual purine (or pyrimidine) NTPs are not distinguishable in the liver on the basis of their 31P NMR chemical shifts, the contributions of UTP and GTP were investigated by HPLC. The changes in liver NTP content measured either by NMR on isolated liver or by HPLC after perchloric acid extraction from the same organ are not significantly different. The total NTP level in normothermic perfused liver is 7.6 +/- 0.2 mumol NTP/g liver dry wt as determined by NMR. In such a liver, ATP + GTP + UTP and ATP contents measured by HPLC are, respectively, 7.9 +/- 1.0 and 6.3 +/- 0.9 mumol/g liver dry wt. This indicates that all NTP is detected by NMR and that a 20% contribution of the signal occurs from UTP + GTP. Under 4-h cold ischemic conditions, NTP visibility remains unchanged, furthermore the UTP + GTP contribution reaches 32% of the whole NTP content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is cellular integrity responsible for the partial NMR invisibility of ATP in isolated ischemic rat liver? 181 6

As an approach to understanding the molecular basis of the pathophysiology of cerebral ischemia, we examined qualitative and quantitative changes in pertussis toxin substrates, Gi1 and G0, in the membrane of rat cerebral cortex after decapitation. Within 1 min after decapitation, the extent of pertussis toxin-catalyzed [32P]ADP ribosylation of the G proteins in the cerebral cortex membrane was significantly decreased and the magnitude of the decrease became slightly larger upon further incubation of the decapitated brain. Addition of guanine nucleotides, GTP and GDP, or the purified beta gamma subunits of transducin to the membranes of control and ischemic cerebral cortex stimulated [32P]ADP ribosylation of the G proteins. The stimulation of [32P]ADP ribosylation in the control situation by guanine nucleotides was almost to the same extent as that in ischemia. However, the stimulation by transducin beta gamma subunits was different; the control stimulation was greater than that in ischemia. In immunoblots probed with antibodies against Gi1 alpha, G0 alpha, and T beta, the immunoreactivity of the corresponding proteins in ischemia was similar to that in control, suggesting that the amounts of G proteins were not changed in ischemia. These results suggest that ischemia accelerates the dissociation of alpha-GDP-beta gamma to alpha-GDP and free beta gamma and causes the denaturation of the dissociated alpha-GDP, thereby decreasing [32P]ADP ribosylation.
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PMID:Ischemia of rat brain decreases pertussis toxin-catalyzed [32P]ADP ribosylation of GTP-binding proteins (Gi1 and G0) in membranes. 189 6

Malignant arrhythmias and the spreading of the infarcted zone in acute myocardial ischemia may be influenced by the sympathetic system. It has been known for quite some time that acute ischemia leads to an increased release of endogenous catecholamines. Adaptive mechanisms at the postsynaptic level such as receptor desensitization, which are operative under normoxic conditions, are abolished in acute myocardial ischemia. On the contrary, three newly characterized, distinct mechanisms lead to a transiently increased activity of the beta-adrenergic system in the early phase of acute ischemia: 1) Functionally coupled beta-adrenergic receptors are rapidly and persistently increased at the cell surface due to the impairment of beta-agonist-promoted uncoupling and internalization. 2) Despite the reversible increase of inhibitory, muscarinic M2 receptors, the inhibitory pathway of the adenylyl cyclase systems becomes ineffective since the coupling protein, Gi, is rapidly impaired. Both the Gi-linked GTPase-activity and the binding of [gamma-35S]GTP are reduced by 25-30% without any loss of the total protein. Stimulatory effects prevail at the G-protein level since in the early period of ischemia the stimulatory G-protein, Gs, remains intact. 3) The adenylyl cyclase is transiently sensitized by about 30%. This increased activity is closely associated with the partially purified enzyme and may be due to a rapidly reversible covalent modification. Prolonged ischemia, in contrast, results in a general decrease of the cyclase activity notwithstanding any changes at the receptor or G-protein level. The individual mechanisms may play distinct and/or complimentary roles in the early sensitization of the adenylyl cyclase system in acute myocardial ischemia.
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PMID:Supersensitivity of the adenylyl cyclase system in acute myocardial ischemia: evaluation of three independent mechanisms. 196 6


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