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)

Naloxone HCl (Nx) improves cardiopulmonary performance, reverses cellular hypoxia, and stabilizes lysosomal membranes in shock states. However, no detailed study has yet explored its potential role in renal ischemia, which is inevitable in transplantation and surgical and nonsurgical conditions associated with hypotension and shock. This functional and microanatomical study was carried out on dogs subjected to renal warm ischemia with contralateral nephrectomy. Group I (control; N = 4) had bilateral renal dissection and right nephrectomy. Groups II-IV had their kidney pedicles cross-clamped for 60 min and then reperfused. Group II (N = 9) ischemic kidneys received no treatment. Group III (N = 6) kidneys were flushed with pure Nx HCl (2 mg/kg) during ischemia. Group IV (N = 6) dogs received one iv Nx bolus (2 mg/kg) before clamping and another dose before declamping. Biopsies for adenine nucleotides, histology, and ultrastructure were obtained before ischemia, before reflow, and 15 min and 7 days after reflow. Serum creatinine and blood urea nitrogen were measured daily. Ischemia induced significant renal dysfunction, which was reversed by systemic Nx. Nx offered a remarkable protection against postischemic structural damage. Seventy percent of Group II cortical sections showed grade 4 acute tubular necrosis (ATN), and severe residual damage after a week. Eighty-three percent of Group IV sections showed grade 1 ATN and no residual damage after a week. One week survival was 33% in Group II and 100% in Group IV. Nx can be useful in prevention of acute renal failure in clinical situations with arterial hypotension and shock.
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PMID:Naloxone in renal ischemia: a functional and microanatomical study. 358 32

The present investigation was undertaken to examine the recovery of functions, spontaneous EEG activity and cerebral ATP content during blood recirculation following cerebral ischemia in rats. The ischemia was induced by bilateral carotid artery 30 min-occlusion 24 hr after the permanent electrocauterization of bilateral vertebral arteries. EEG spectral analysis was performed by the Berg transform. The recovery of EEG activity was assessed by the time elapsing from the onset of blood recirculation until the delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz) or beta (13-32 32 Hz) band reappeared and the relative proportion of the four bands at 45 and 60 min after recirculation. Following the 20 min recirculation, the brains were frozen in situ with liquid nitrogen and then stored at -80 degrees C for later extraction for analysis. Concentrations of ATP in the cerebral cortex were determined with enzymatic methods. In animals administered FO-1561 (10 approximately 100 mg/kg, i.v.) simultaneously with blood recirculation, the reduction of time elapsing until reappearance of the theta, alpha and beta bands, the decrease in proportion of the delta band and the increase in that of the theta, alpha and beta bands which indicated the facilitation of transition to the normal state were observed. In animals administered FO-1561 (100 mg/kg), the improvement of ATP content was detected. These results demonstrate that FO-1561 may have a beneficial effect on the recovery from dysfunctions due to cerebrovascular disorder.
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PMID:[Effect of S-adenosyl-L-methionine sulfate tosylate (FO-1561) on functional recovery after transient cerebral ischemia in rats]. 367 20

It has been proposed that oxygen free radicals mediate damage that occurs during postischemic reperfusion. Recombinant human superoxide dismutase (r-h-SOD) has been shown to be effective at reducing reperfusion injury, but it is not known if this infused enzyme actually reduces oxygen free radical concentrations in the myocardial tissue. Electron paramagnetic resonance spectroscopy was used to directly measure the effect of r-h-SOD on free radical concentrations in the postischemic heart. Hearts were freeze clamped at 77 degrees K after 10 min of normothermic global ischemia followed by 10 s of reflow with control perfusate (n = 7) or perfusate containing 60,000 U r-h-SOD (n = 7). The spectra of these hearts exhibited three different signals: signal A isotropic, g = 2.004, identical to the carbon-centered ubiquinone free radical; signal B anisotropic with axial symmetry, g parallel = 2.033, g perpendicular = 2.005, identical to the oxygen-centered alkyl peroxyl free radical; and the signal C an isotropic triplet, g parallel = 2.000, an = 24 G, similar to a nitrogen-centered free radical such as a peroxyl amine. With r-h-SOD administration the concentration of the oxygen free radical, signal B, was reduced 49% from 6.8 +/- 0.3 microM to 3.5 +/- 0.3 microM (P less than 0.01) and the concentration of the nitrogen free radical, signal C, was reduced 38% from 3.4 +/- 0.3 to 2.1 +/- 0.3 microM (P less than 0.01). The concentration of the carbon-centered free radical, signal A, however, was increased 51% from 3.3 +/- 0.2 to 5.0 +/- 0.2 microM (P less than 0.01). Identical reperfusion with peroxide-inactivated r-h-SOD did not alter the concentrations of free radicals indicating that the specific enzymatic activity of r-h-SOD is required to decrease the concentrations of reactive oxygen free radicals. Additional measurements performed varying the duration of reflow demonstrate a burst of oxygen free radical generation peaking at 10 s of reperfusion. r-h-SOD entirely abolished this burst. These studies demonstrate that superoxide-derived free radicals are generated during postischemic reperfusion and suggest that the beneficial effect of r-h-SOD is due to its specific enzymatic scavenging of superoxide free radicals.
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PMID:Recombinant superoxide dismutase reduces oxygen free radical concentrations in reperfused myocardium. 368 May 25

The cerebral cortical cup technique was used to monitor changes in adenosine and inosine levels in the rat cerebral cortex during periods of hypoxia, anoxia, or hemorrhagic hypotension. Basal levels of adenosine and inosine in cortical perfusates stabilized within 10 min at concentrations of 30-50 and 75-130 nM, respectively. Comparable levels were observed in normal CSF collected from the cisterna magna. Reductions in the oxygen content of the inspired air (14, 12, 8, and 5% oxygen) resulted in increases in the adenosine and inosine levels in the cortical perfusates, the magnitude of the increase being progressively more pronounced with greater reductions in the oxygen content. Cerebral anoxia/ischemia, induced by 100% nitrogen inhalation, caused a rapid increase in the adenosine and inosine contents of the cortical perfusates. Hemorrhagic hypotension (46.1 +/- 1.7 mm Hg) of 5 min duration did not result in an elevated adenosine or inosine release. The results suggest that interstitial fluid adenosine levels are likely to be in the low nM range in the normoxic animal and are capable of rapid increases during hypoxic or anoxic episodes. The findings support the adenosine hypothesis of CBF regulation.
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PMID:Increases in cerebral cortical perfusate adenosine and inosine concentrations during hypoxia and ischemia. 369 25

The ability of anipamil, a calcium channel blocker, to protect ischemic myocardial tissue was investigated in pentobarbital anesthetized cats. Two bolus injections of anipamil (1.0 mg/kg i.v.) or their vehicle (i.e., 95% ethanol) were given 30 and 150 min post-ligation of the left anterior descending coronary artery. Anipamil significantly reduced the elevated S-T segment elevation and T wave amplitude suggesting a moderating influence on cellular ischemia. The drug also significantly blunted the loss in myocardial creatine kinase activity and amino-nitrogen concentrations from ischemic myocardial tissue, compared to cats receiving only the vehicle. These changes are suggestive of a cardioprotective effect of this calcium channel blocker. Since no significant change in the pressure rate index was seen with anipamil, a decrease in myocardial oxygen demand does not appear to be the major mechanism of the cardioprotective action of the agent. Therefore, anipamil protected the heart from ischemic damage, possibly by a direct cytoprotective action.
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PMID:Cardioprotective actions of a new calcium channel blocker in acute myocardial ischemia. 370 65

To evaluate the combined effects of a brief ischemic insult and cyclosporine, four groups of male Munich Wistar rats were given: a) parenteral cyclosporine (60 mg/kg i.p.) for 4 days following 20 minutes of bilateral renal ischemia, b) the castor oil cyclosporine vehicle in a comparable volume and the same ischemic insult, c) saline in the same volume and ischemia, or d) saline and sham surgery. The cyclosporine animals ate and drank poorly, and therefore the other groups were pair-fed and watered with them. The cyclosporine-ischemia group developed significant renal failure. The other groups exhibited only a mild rise in blood urea nitrogen. Tubular vacuolization was a prominent feature in the cyclosporine and vehicle groups, but not in the saline groups. Vacuolization was correlated with severity of renal impairment. Lipid stains showed that many of the vacuoles contained lipid. Eosinophilic cytoplasmic inclusions were seen only in the cyclosporine or vehicle- (castor oil) treated animals. These findings emphasize the probable functional importance of tubular lesions in cyclosporine-induced acute renal failure, and suggest that the castor oil vehicle of parenteral cyclosporine may have renal effects of its own.
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PMID:Acute renal failure produced by combining cyclosporine and brief renal ischemia in the Munich Wistar rat. 370 29

The purpose of this investigation was to test whether alterations of intravascular volume change renal susceptibility to ischemic injury. Acute volume depletion (2% body weight; by furosemide injection or by hemorrhage) or volume expansion (10% body weight; by saline infusion) was induced in Sprague-Dawley rats. The effects of these interventions on renal blood flow (RBF), mean arterial blood pressure (MAP), glomerular filtration rate (GFR), and renal adenine nucleotide content were assessed by comparison with values observed in euvolemic control rats. Volume-depleted, volume-expanded, and euvolemic control rats were also subjected to 25 minutes of bilateral renal artery occlusion (RAO). The severity of ischemic injury was assessed 24 hours later (by determination of GFR, blood urea nitrogen, creatinine, and histology). Before RAO, the volume-depleted rats had significant reductions in GFR (33%), MAP (20% to 45%), and RBF (52% to 72%), but renal adenosine triphosphate (ATP) content was totally preserved. Both groups of volume-depleted rats had normal susceptibility to RAO, compared with the euvolemic controls. Before RAO, volume expansion had no significant effect on GFR, MAP, or RBF, but it decreased renal ATP content by 21%. In addition, volume expansion significantly exacerbated the ATP depletion that occurred both during and after RAO. Nevertheless, the volume-expanded rats were almost totally protected against ischemia. It is concluded that the kidney can tolerate severe volume depletion without apparent deterioration in tubular cell energetics or a change in renal susceptibility to superimposed ischemic injury. Acute volume expansion can protect against ischemic injury, despite lowering renal ATP content.
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PMID:Alterations of intravascular volume: influence on renal susceptibility to ischemic injury. 371 26

It is known that pentobarbital, which has been used for severe brain infarct or head injury as a brain protective drug, inhibits the increase of free fatty acids (FFAs) liberated from membrane phospholipids during ischemia. However, the mechanisms of FFA liberation from phospholipids and the mode of action of pentobarbital are still unclear. Therefore we have investigated the effects of induction of global ischemia and pentobarbital pretreatment upon lipid metabolism in rat brain. Brain ischemia was evoked by rat decapitation and pentobarbital (60 mg/kg) was administered i.p. for 15 min prior to decapitation. Removed brains were incubated for 1, 5, 15 or 30 min at 37 degrees C and then quickly frozen in liquid nitrogen. After extraction of lipids from the brains, neutral lipid and phospholipid compositions were analyzed by thin-layer and gas-liquid chromatography. The results demonstrated that FFAs, either unsaturated or saturated, were rapidly accumulated in the brain during early period of ischemia, but attenuated significantly by pentobarbital pretreatment. Pentobarbital attenuated the accumulations of stearic and arachidonic acids, with little effect on palmitic and oleic acids. Diacylglycerol (DG), which is considered to be as a plausible candidate for the source of FFA, was also produced in the ischemic brain, and its acyl chain composition was similar to that of liberated FFAs. Furthermore, the increase of DG was inhibited significantly by pentobarbital anesthesia. In particular, pentobarbital attenuated the accumulation of DG enriched in arachidonic and stearic acids. This fatty acyl composition resembled the principal composition of phosphatidylinositol (PI) in rat brain.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of pentobarbital on brain lipid metabolism during global ischemia]. 373 Feb

Nervous conduction was measured in 27 subjects before and after compression in ternary mixture (helium, nitrogen and oxygen) ranging from 5,5 to 12 ATA. Among the eleven parameters studied, three showed an acceleration of the nervous conduction in the distal part of the sensitive and motor fibers. Although no precise mechanism can be established, different factors, in particular the role of ischemia, are discussed.
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PMID:[Changes in nerve conduction velocity as a result of hyperbaria in man]. 376 38

Isolated preparations of rabbit interventricular septum were perfused through the coronary arteries with oxygenated Tyrode's solution and placed in a tissue bath where they were superfused as well. Transmembrane potentials were simultaneously recorded from the subendocardium with two flexibly mounted microelectrodes, one from a superficial cell, and the other from a deep cell. Ischemia was produced by stopping coronary flow while superfusion with oxygenated Tyrode's solution was maintained. After a 7 to 12 min ischemic period, the preparation was fixed by coronary perfusion with fixative while the microelectrodes remained in place. After fixation, the microelectrodes were withdrawn. Appropriate tissue blocks were cut in 4 micron serial sections and the microelectrode track was followed until the tip position was identified. Transmembrane potentials during ischemia were divided into two categories: "border zone" potentials (resting membrane potential [RMP] 73 +/- 3 mVe, action potential amplitude [APA] 81 +/- 13 mV, action potential duration [APD] 116 +/- 48 msec, n = 12) and "ischemic" potentials (RMP 53 +/- 4 mV, APA 44 +/- 11 mV, APD 102 +/- 42 msec, n = 8). Ischemic potentials were recorded from cells at depths greater than 560 micron below the endocardial surface and border zone potentials were recorded in a layer at between 130 and 650 micron below the surface. In a separate series of experiments, extracellular concentrations of K+ and pH were measured with ion-sensitive electrodes at different depths and, after a 10 min period of ischemia, part of the septum was placed in liquid nitrogen to allow determination of phosphocreatine (PC) levels in successive 50 to 100 micron layers. After 10 min of ischemia, extracellular K+ gradually increased from 4 to 9 mM in endocardium to a depth of 600 micron, pH fell from 7.4 to 6.6 over the same distance, and PC decreased to very low, stable levels at only 800 micron. It is concluded that in the first 10 min of acute ischemia, an endocardial border zone exists of 40 to 60 cell layers in which transmembrane potentials are affected relatively little by ischemia. Within this electrophysiologic border zone extracellular K+ was lower than 9 mM, pH was higher than 6.6, and tissue content of PC was not lower than 40% of normal. In layers deeper than 600 micron, with further development of a metabolic gradient, action potentials became markedly depressed. This electrophysiologic inhomogeneity within the ischemic subendocardium could be a factor in arrhythmogenesis during the first minutes of ischemia.
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PMID:The subendocardial border zone during acute ischemia of the rabbit heart: an electrophysiologic, metabolic, and morphologic correlative study. 376 71


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