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

Both Trolox (a water-soluble analogue of alpha-tocopherol) and ascorbic acid were more effective than superoxide dismutase or catalase in protecting myocyte cell cultures from free radical attack (induced by hypoxanthine and xanthine oxidase). In a canine model of two hours of left anterior descending coronary artery occlusion followed by four hours of reperfusion, Trolox and ascorbic acid reduced the area of infarction within the area at risk. The Trolox group received 500 mL of deoxygenated saline solution containing 2.0 g of Trolox, 3.0 g of ascorbic acid, and 18 mg of EDTA (ethylenediaminetetraacetic acid) infused into the ascending aorta 30 seconds before and four minutes after reperfusion. Saline controls received 500 mL of deoxygenated saline solution containing 18 mg of EDTA. The angioplasty group had unmodified reperfusion by simple release of the occlusion. The area at risk and the area infarcted were estimated with Evans blue and triphenyl tetrazolium hydrochloride stains, respectively. The ratio of the area infarcted to the area at risk was significantly lower with Trolox (angioplasty, 30.4% +/- 5.1%; saline, 20.8% +/- 2.9%; and Trolox, 8.7% +/- 4.0%; p less than 0.01). In summary, the antioxidants Trolox and ascorbic acid effectively reduced myocardial necrosis after ischemia.
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PMID:Myocardial salvage with trolox and ascorbic acid for an acute evolving infarction. 271 29

We investigated the earliest time at which irreversible damage takes place after hypoxia-ischemia in the Levine preparation of rats. In 60 rats anesthetized with chloral hydrate and maintained at one of three body temperatures, we unilaterally ligated the left common carotid artery and placed electrodes in the striatum to measure impedance (reflecting the extracellular space) during hypoxia, recovery, and/or cardiac arrest. We measured blood gases and pH at regular intervals during hypoxia in 47 rats and assessed blood-brain barrier function with Evans blue and tissue damage using Na+:K+ ratios. Shortly after hypoxia, impedance normalized in 24 rats without brain damage (normal Na+:K+ ratios, 4 hours of recovery). Sustained elevation of striatal impedance during recovery in six rats was related to an elevated Na+:K+ ratio and a disrupted blood-brain barrier. Damage was not obviously related to blood gases, pH, or the net reduction of the extracellular space during hypoxia. Hypothermia in 17 rats prevented impedance changes, and no striatal damage was found. Thus, irreversible brain damage very likely occurs during or very shortly after hypoxia. Persistent reduction of the extracellular space indicates tissue damage and can be used to monitor potential in vivo therapeutic measures.
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PMID:Rat striatal cation shifts reflecting hypoxic-ischemic damage can be predicted by on-line impedance measurements. 279 69

This study compared arrhythmias induced by acute ischemia in Langendorff preparations of normal and hypertrophied rat hearts. Left ventricular pressure overload was induced by partial ligation of the abdominal aorta 6 to 8 weeks prior to study. The ratio of left ventricular weight to body weight (LVW/BW) and systolic blood pressure (SBP) were significantly higher in two groups of rats with hypertrophied hearts (moderate hypertrophy: 2.68 +/- 0.06 mg/g, 182 +/- 3 mmHg; severe hypertrophy: 3.31 +/- 0.03 mg/g, 238 +/- 5 mmHg) than in normal hearts (2.18 +/- 0.03 mg/g, 125 +/- 3 mmHg), while there were no differences in body weights. During 30 min of ischemia produced by left coronary artery occlusion in the Langendorff preparations, ventricular fibrillation occurred in six of 20 (30%) normal, six of nine (67%) moderately hypertrophied, and 14 of 14 (100%) severely hypertrophied preparations (P less than 0.001 normal vs severely hypertrophied). Tachyarrhythmias occurred in 15 of 20 (75%) normal, eight of nine (89%) moderately hypertrophied, and 14 of 14 (100%) severely hypertrophied hearts. Heart rate and coronary efflux before and during the ischemic period did not differ between normal and hypertrophied hearts. The ratio of non-perfused to perfused areas of the left ventricle, measured by Evans blue dye staining and with computerized planimetry, also was not different for normal (57.6 +/- 2.3%) and hypertrophied hearts (moderate hypertrophy 62.5 +/- 3.3%, and severe hypertrophy 59.1 +/- 2.0%). Additional control studies using larger hearts from older rats also indicate that myocardial mass was not an important determinant of ischemic arrhythmias in hypertrophy. Prolongation of endocardial and epicardial conduction time during 30 min of ischemia was not different between normal and hypertrophied hearts. Action potential duration and refractory periods were significantly longer in ventricular cells of hypertrophied hearts than in normals, and superfusion with hypoxia/zero glucose solution shortened these parameters to a greater extent in hypertrophied cells. These results lead us to conclude that hypertrophied hearts have a greater susceptibility to ventricular fibrillation during acute ischemia, and that dispersion of refractoriness may play a role in this phenomenon.
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PMID:Susceptibility of hypertrophied rat hearts to ventricular fibrillation during acute ischemia. 296 21

The goals of this research were to develop a within-subject test of spatial working memory and performance for the rat in a T-maze, based on a delayed alternation, or "win-shift" foraging strategy. Using this model, specific aims were to compare the effects of: (1) age, (2) basal forebrain, medial septal, and amygdala lesions, (3) four vessel occlusion (4-VO), forebrain ischemia, and (4) physostigmine, scopolamine, arecoline, piracetam, and clonidine on memory and performance of young middle-aged, and old rats. Aging significantly impaired working memory and performance of Long-Evans rats. Memory of septal and basal forebrain, but not of amygdala lesioned rats was significantly impaired without effects on performance. Transient, 4-VO forebrain ischemia produced significant memory impairment, without effects on performance, and highly selective CA1 cell loss in the hippocampus. Physostigmine enhanced working memory in middle-aged and old rats. Scopolamine impaired memory in young, middle-aged, and old rats. Physostigmine reversed the scopolamine impairments of working memory. Arecoline enhanced memory in old rats without effects on performance. Piracetam and clonidine had no direct effects on memory, but piracetam increased and clonidine decreased speed of performance. From the aging, lesion, ischemia, and drug studies it was concluded that there was a convergence of evidence from 4 different approaches for a critical role for the hippocampus, particularly the CA1 fields, in spatial working memory.
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PMID:An animal model of human-type memory loss based on aging, lesion, forebrain ischemia, and drug studies with the rat. 306 74

The brain lesions in stroke-prone spontaneously hypertensive rats (SHRSP) are characterized by multifocal microvascular and spongy-cystic parenchymal alterations particularly in the gray matter. An essential feature of the lesions is the presence of edema with massive extravasation of plasma constituents as evidenced by specific gravity measurements, Evans blue technique and immunohistochemistry. The nerve cell injury occurring in the brain lesions in SHRSP is further characterized by light and electron microscopy in the present study. Two types of neuronal changes were seen within the blood-brain barrier (BBB) leakage sites. A small number of neurons with dark condensed nucleus and cytoplasm were found most often at the periphery of recent lesions. The majority of injured neurons were pale and showed intracellular edema confined to the dendrites and perikarya sparing axons and synapses. Their nuclei were well preserved with finely dispersed chromatin. The swollen and watery cell processes of neurons and astrocytes gave a spongy appearance to the neuropil. The intracellular edema seemed to result in cytolysis. The results suggest that primary anoxia-ischemia is not the major pathogenetic mechanism behind the nerve cell injury in severely hypertensive SHRSP, rather it is the massive BBB leakage and consequent brain edema that causes cytolytic destruction of neurons. Secondary focal ischemia as a consequence of occlusion in microvessels may, however, contribute to the nerve cell destruction.
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PMID:Nerve cell injury in the brain of stroke-prone spontaneously hypertensive rats. 321 25

We investigated the effect of the sodium channel blocker, tetrodotoxin, in two animal models of brain pathology. In the first, an acute model, we recorded the interstitial brain potential in the striatum of rats after cardiac arrest. The time of deflection of this potential, an indication of changes in cerebral cation concentrations, was determined in control rats, and in rats pretreated with intrastriatal tetrodotoxin. In control rats a deflection of the brain potential was noted 2 min after cardiac arrest; tetrodotoxin pretreatment delayed this deflection to about 5 min. The second, a survival model, was based on the Levine preparation in rats. A combination of ischemia and hypoxia produced unilateral, cerebral infarcts, which were characterized by a decrease of brain [K+], and by increases of [Ca2+] and [Na+] and thus of the Na+:K+ ratio. Data on the cation shifts, determined by chemical assay methods, were complemented by those of more conventional methods of assessment of brain damage, such as the determination of survival, of Evans blue staining, and of brain water content. Cation shifts could be prevented locally by tetrodotoxin. In conclusion, the drug can, at least partially, prevent the detrimental effects of an ischemic insult. In addition, our results showed that protective effects observed in the acute model may sometimes offer an indication of the effects to be expected in the survival model. Furthermore, the effect of tetrodotoxin on the brain potentials in the acute model showed that its protective action in the survival model may be brought about by delaying cell depolarization and by shortening the actual duration of the depolarized state. We conclude that Na+ influx and, consequently, neurotransmission may play a crucial role in the development of cerebral damage.
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PMID:Cerebral cation shifts in hypoxic-ischemic brain damage are prevented by the sodium channel blocker tetrodotoxin. 333 36

There is controversy over the existence of a lateral "border zone" of intermediately injured tissue in the developing myocardial infarct (MI). The authors attempted an ultrastructural demonstration of this zone in serial subepicardial biopsies from developing MIs in dogs subjected to 90 minutes, 6 hours, or 24 hours of left anterior descending coronary artery ligation (4 dogs per group). After ligation, 400,000 units of horseradish peroxidase was infused through the left atrial appendage as a blood flow marker, to allow distinction of perfused and ischemic myocytes under electron microscopy. Evans blue stain was infused in the same way for gross guidance in harvesting biopsies across the lateral margins of the ischemic region. Interdigitation of perfused and ischemic tissue was observed over a lateral margin 6 mm wide, which caused admixture of perfused and ischemic myocytes in biopsies from this region. Ultrastructural ischemic injury was graded on a five-level qualitative scale (normal, mild, moderate, severe, lethal). Perfused myocytes from control and border sites were equivalently well preserved (79% normal, 21% mild injury, n = 353). Ischemic myocyte injury increased with duration of ischemia. At 90 minutes, 65% of ischemic myocytes had mild injury, 35% moderate (n = 138); at 6 hours, 17% of ischemic myocytes had moderate injury, 81% severe, 2% lethal (n = 115); at 24 hr, 100% of ischemic myocytes had lethal injury (n = 148). Severity of ischemic myocyte injury did not vary from the lateral border to the center of the ischemic region: there was no lateral "border zone." However, if myocytes were not separated into perfused and ischemic subpopulations before statistical comparison of biopsy site to severity of injury, false evidence of a "border zone" was obtained.
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PMID:The "border zone" in myocardial infarction. An ultrastructural study in the dog using an electron-dense blood flow marker. 338 78

Peak aortic blood velocity (Vel), peak acceleration (Acc), stroke volume (SV), and left ventricular (LV) ejection fraction (EF) have been used as noninvasive indicators of global LV performance. The purpose of this study was to determine which of these indices of LV performance relates best to the extent of LV ischemic mass at risk. Studies were performed in 24 open-chest anesthetized dogs. Acute ischemia was produced by occlusion of various levels of the left anterior descending and circumflex coronary arteries. LV ischemic mass, measured as a percent of total LV mass, was delineated by injection of Evans blue dye into the nonischemic zone. Acc and Vel were measured with continuous-wave Doppler ultrasound. EF was measured angiographically. All parameters were measured during a control period and within 6 minutes of coronary occlusion. The percent change during ischemia of each parameter relative to control (% delta) was calculated. The correlation coefficient between the percent ischemic mass at risk and % delta Acc was 0.88. It was 0.84 for % delta EF, 0.77 for % delta Vel, and 0.17 for % delta SV. These results indicate that among the various global indices of LV performance that have been used noninvasively, Acc correlates most closely with the extent of LV ischemic mass at risk.
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PMID:Peak aortic blood acceleration reflects the extent of left ventricular ischemic mass at risk. 355 72

Nimodipine is known to improve postischemic cerebral blood flow (CBF) and neurologic outcome in experimental animals. Whether or not the two observations are related is unknown. This study searched for a possible improved rate of brain metabolic recovery in animals treated with nimodipine postischemia. Complete cerebral ischemia was produced for 11 min in 16 dogs, followed by reperfusion for 70 min. Prior to ischemia, glucose was administered (0.75 g X kg-1) in 12 dogs. Half of the glucose-treated dogs were given i.v. nimodipine, beginning 5 min postischemia (10 micrograms X kg-1 bolus followed by 1 microgram X kg-1 X min-1). The other half were given only saline postischemia. The remaining four dogs were given no glucose and received saline only postischemia. In all dogs, serial brain biopsies were taken at 2, 20, 40, and 70 min postischemia. In 5 dogs, the integrity of the blood-brain barrier (BBB) was tested by injection of Evans blue dye and postmortem examination of the brains. Brain biopsies were assayed for concentrations of phosphocreatine, ATP, ADP, AMP, glucose, lactate, and pyruvate. In all dogs, there was rapid restoration of a normal brain energy state following reperfusion. Brain lactate had returned to near normal in all dogs by 70 min postischemia, and the rate of lactate depletion was not different between groups. The integrity of the BBB was only minimally affected. A portion of the brain lactate was converted to pyruvate rather than crossing the BBB.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nimodipine does not affect cerebral lactate levels following complete ischemia in dogs. 365 2

Recently there is the hypothesis proposing that ischemic brain damage is associated with intracellular accumulation of calcium (Ca++). Therefore a variety of experiments have been carried out to investigate whether a Ca++-entry blocker was able to protect against brain damage caused by ischemia. The purpose of the present experiment is to study the protective effects of a Ca++ antagonist, flunarizine, on cerebral ischemia. In this experiment fifteen dogs were subjected to ischemia, using the "canine model of the completely ischemic brain regulated with a perfusion method" in which the cerebral blood flow (CBF) can be fully regulated. Five animals served as untreated controls, ten received treatment with flunarizine (1 mg/kg in five dogs and 3 mg/kg in five dogs, respectively). This agent was administered intravenously 20 minutes prior to the production of ischemia, when cerebral blood flow was reduced to one-tenth its normal value while monitoring CBF by means of a laser-Doppler flow meter. After one hour CBF was restored and the recovery of electrical activity of the brain and the degree of brain swelling were observed for three hours. At the end of the experiments, the degree of extravasation of Evans blue in the excised brain was examined. With regard to the recovery of EEG, no recovery of EEG was seen subsequent to recirculation except one dog in the control group. Whereas in the groups treated with flunarizine, remarkable recovery of EEG was found following recirculation in a dose dependent fasion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cerebral protective effect of flunarizine in a canine model of cerebral ischemia]. 368 6


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