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

Recently developed rodent models of acute subdural hematoma have shown an associated large area of infarction underlying the clot. Excitotoxic processes have been postulated to play an important role in the extensive cell death seen with these models. However, whether increased pressure, vasoactive effects, or toxicity of the blood itself is responsible for initiating or sustaining these processes remains unclear. To study the effect of blood itself, an opaque layer of autologous clot was placed on the widely exposed parietal cortex of 15 Long-Evans rats and left in place for 72 h. In control animals the cortical surface was exposed but no blood was placed and contact with blood products was carefully limited. These animals were compared to a group in whom blood was injected into the closed subdural space. Histologic analysis showed that the majority of the cortex in both control and experimental animals in the open cranial model group appeared normal. Scattered small, discrete hemorrhagic lesions on the cortical surface of both control and experimental animals were seen, which had the appearance of focal mechanical trauma or vessel avulsion. There was no significant difference in average volume of lesions between experimental and control animals (9.1 versus 9.7 mm3, p = 0.85). No areas of infarction or selective neuronal loss were seen. In comparison, animals in which blood was injected into the subdural space had significantly larger lesions underlying clot, averaging 133.6 mm3 in volume (p < 0.0003). Blood in prolonged contact with the cortical surface in the absence of increased pressure, ischemia, or other insult is insufficient to cause underlying infarction like that seen when a similar volume of blood is injected into the closed subdural space.
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PMID:Acute subdural hematoma: is the blood itself toxic? 772 66

We report on the renal function and regional extravasation of albumin-bound Evans blue dye (EB) in the kidneys of anesthetized dogs following 30 min occlusion of the left renal artery. Left kidney (LK) function was halted and no change in right kidney (RK) function was observed during ischemia. Clearances of para-amino-hippurate and inulin from the LK were significantly (P < 0.01) less than control after 10 min of reperfusion, 22.6 +/- 6.8 vs 90.1 +/- 7.8 and 9.0 +/- 2.9 vs 34.2 +/- 2.1 ml/min, respectively. Renal hemodynamic parameters never did fully recover in subsequent periods but filtration fraction was unchanged from control throughout the reperfusion period. Urine flow and sodium excretion from the LK was significantly (P < 0.01) less than control values after 10 min of reperfusion, 0.41 +/- 0.14 vs 0.80 +/- 0.08 ml/min and 60 +/- 21 vs 161 +/- 8 mu eq/min, respectively, but fully recovered in subsequent periods. Significant (P < 0.01) decrease from control values in the LK content of EB was observed in the inner medulla and papilla regions after 30 min of reperfusion, 586 +/- 60 vs 763 +/- 51 and 549 +/- 54 vs 741 +/- 52 micrograms/EB/g dry tissue, respectively. After 60 min of reperfusion in the LK, significant (P < 0.05) changes from control in EB content were evident exclusively in the outer medulla, increasing from 398 +/- 56 to 491 +/- 17 micrograms/EB/g dry tissue, respectively. A general edema in the LK, measured as an increase in the ratio of wet/dry tissue weight, became evident only after 60 min of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal reperfusion injury: sequential changes in function and regional albumin extravasation. 773 94

An efficient, unbiased stereological method for estimating and evaluating volumetric parameters of cortical infarction is presented. Long-Evans rats were subjected to a standard procedure for achieving focal cerebral ischemia, consisting of permanent ligation of the right middle cerebral artery and temporary occlusion of both common carotid arteries. Animals were killed 24 h later by perfusion fixation and the brains were embedded in celloidin, serially sectioned at 60 microns and stained with Cresyl violet. All cases showed identifiable areas of infarction of variable extent within the territory of the right middle cerebral artery. Involvement of allocortical or subcortical structures was variable and in three cases there were small foci of infarct in the contralateral hemisphere. The absolute volumes of the infarcted tissue and of the spared cortex of both hemispheres were obtained by means of an unbiased estimator of volume based on Cavalieri's principle. The best estimate of the actual amount of infarcted cortex was found to be given by the volume ratio between the spared cortex of the right (infarcted) hemisphere and the total cortex of the left (control) hemisphere. This approach avoided the error introduced by the accompanying edema and decreased the observed interanimal variance. Sample size predictions for therapeutic-pharmacological trials show that relatively few animals would be needed using the model of ischemia and quantitative morphometry presented here to detect a 30-40% change in infarct volume.
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PMID:Morphometric study of focal cerebral ischemia in rats: a stereological evaluation. 775 83

Arachidonic acid metabolites are believed to be important mediators of tissue injury during reperfusion after cerebral ischemia. To determine whether inhibiting the oxygen-dependent metabolism of arachidonic acid would reduce reperfusion injury, we administered the mixed cyclooxygenase-lipoxygenase inhibitor BW755C (3-amino-1-[m(trifluoromethyl)phenyl]-2-pyrazoline) near the time of reperfusion in a rat model of temporary focal ischemia. The duration of ischemia + reperfusion was 2 hours + 22 hours, 3 hours + 3 hours, or 3 hours + 21 hours. The effects of drug or saline treatment on infarct volume, blood-brain barrier permeability, and blood flow were determined. Cortical blood flow was monitored with laser Doppler flowmetry and blood-brain barrier permeability was evaluated by the Evans blue dye method. Infarct volume was determined in all groups by computerized image analysis of Nissl-stained sections. We found that BW755C treatment significantly attenuated delayed postischemic hypoperfusion in the 3 + 3 group (p < 0.05) and reduced the volume of Evans blue dye staining in the cortex (p < 0.01) and basal ganglia (p < 0.05). Hemispheric swelling was reduced in all treatment groups (p < 0.01), as was total infarct volume in the ischemic hemisphere (p < 0.05). These results support the hypothesis that arachidonic acid metabolites contribute to acute postischemic reperfusion injury and suggest that using a mixed cyclooxygenase-lipoxygenase inhibitor as an adjunct to thrombolytic or revascularization therapy could lengthen the ischemia time after which reperfusion is beneficial.
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PMID:Attenuation of postischemic brain hypoperfusion and reperfusion injury by the cyclooxygenase-lipoxygenase inhibitor BW755C. 778 58

Using a rat lung model, we sought to characterize the time course for ischemia-reperfusion injury and the role of neutrophils in the development of injury. Adult male Long-Evans rats underwent left thoracotomy with dissection and clamping of the left pulmonary artery, bronchus, and vein for 90 min, resulting in complete left lung ischemia. The lungs were then ventilated and reperfused for up to 4 hr. Time-matched sham animals underwent the identical thoracotomy and hilar dissection, but the lungs were not rendered ischemic. Using vascular permeability of 125I-labeled bovine serum albumin as a measure of reperfusion injury, a bimodal pattern of injury was observed. Compared to sham controls, animals undergoing ischemia-reperfusion demonstrated a significant early phase of lung injury at 30 min of reperfusion (P < 0.0001), followed by partial recovery. A second peak of lung injury was noted after 4 hr of reperfusion (P < 0.001). Myeloperoxidase activity in reperfused lung tissue, a measure of neutrophil sequestration, increased during the reperfusion time course. To determine the role of neutrophils in the development of lung reperfusion injury, additional animals undergoing the identical ischemia-reperfusion protocol received either rabbit anti-rat neutrophil serum or preimmune serum the day prior to operation. Profound neutropenia (< 75/mm3 blood) was confirmed by differential leukocyte counts. Neutropenia had no protective effect against microvascular permeability at 30 min of reperfusion, but there was a significant reduction in lung injury at 4 hr (P < 0.005). We conclude that, during lung ischemia-reperfusion, there is a bimodal pattern of injury, consisting of both neutrophil-independent and neutrophil-mediated events.
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PMID:Pattern of injury and the role of neutrophils in reperfusion injury of rat lung. 779 51

Animal models of brain stem ischemia are needed for pathophysiological study and evaluation of treatment; few such models are available currently. A new canine model of hindbrain ischemia and reperfusion is introduced in this article. Through an anterior cervical approach, the basilar artery was surgically exposed in 18 dogs. The posterior communicating and superior cerebellar arteries were embolized with cyanoacrylate glue to isolate the posterior circulation from the anterior circulation. Reversible hindbrain ischemia was induced in 14 dogs by the temporary clipping of the vertebral and ventral spinal arteries for various periods (10-30 min), then the clips were removed and reperfusion was achieved for 5 hours. In all 14 dogs, the hindbrain ischemia was confirmed by the decreased perfusion pressure in the basilar artery (< 10 mm Hg), the diminished regional cerebral blood flow as measured with a laser Doppler flowmeter at the medulla oblongata (< 10 ml/100 g/min), the flattened brain stem auditory evoked potentials, and the increased leakage of Evans blue dye from tissue. These parameters did not change in the four control dogs. The changes in brain stem auditory evoked potentials were closely related to the length of ischemic interval; after 10 minutes of ischemia, reperfusion fully reversed the changes in brain stem auditory evoked potentials, but 20-minute and 30-minute ischemic intervals partially or totally depleted the brain stem auditory evoked potentials. Delayed postischemic hypoperfusion occurred in all five dogs that underwent the 30-minute ischemic interval. The early physiological changes in this model allowed us to estimate the severity of brain stem ischemia and the resulting damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A canine model of acute hindbrain ischemia and reperfusion. 779 92

Adhesion of leukocytes to the endothelium can occur in a few hours after the onset of ischemia, and the actions of leukocytes have been suggested to aggravate reperfusion injury. Adhesion is a prerequisite for the harmful leukocyte actions. Rapid mediation of leukocyte adhesion and aggravation of reperfusion injury can occur through production of platelet-activating factor (PAF). The authors hypothesized that prevention of leukocyte adhesion during ischemia reperfusion would have beneficial effects and that these effects might be enhanced by a PAF antagonist. To test this hypothesis, rabbits were anesthetized with pentobarbital and subjected to severe spinal cord ischemia (25 minutes) followed by 30 minutes of reperfusion, at which time either vehicle, antibody against the CD11/CD18 (anti-CD) leukocyte adhesion molecule (1 mg/kg), or the anti-CD and PAF antagonist, WEB 2086 (3 mg/kg), was administered intravenously and the animals were monitored for 6.5 hours. Using a score from 0 to 5, recovery of motor function was improved at 5.5 hours by the CD antibody (2.0 +/- 0.5 versus 0.4 +/- 0.2 in the six animals in the vehicle group, p < 0.05). No further improvement was induced by WEB 2086 in the six anti-CD treated animals (1.6 +/- 0.7). Spinal cord blood flow (laser Doppler flowmetry) at 6 hours was at the preischemic level in the control animals (-7% +/- 20%), but clearly increased in the anti-CD group (+73% +/- 29%, p < 0.5). The severity of blood-brain barrier damage in the spinal cord gray matter was decreased by the treatments. Extravasation of intravenously injected Evans blue albumin (EBA), measured by detection of EBA fluorescence, was reduced by approximately 50% in both treated groups (p < 0.05). The number of morphologically normal motor neurons in the lumbar anterior horns of the infarcted spinal cord showed protection in the seven animals in the anti-CD treated group at 6.5 hours: 12.7 +/- 1.7 versus 5.3 +/- 1.6 (vehicle), p < 0.05 without an additional effect by PAF antagonist 12.2 +/- 2.6 (anti-CD + WEB 2086). Our results suggest that ultraacute treatment of reperfusion injury based on special inhibition of leukocyte effects may be beneficial. Platelet-activating factor antagonism failed to enhance this therapeutic effect, which may suggest dependency on a common mechanism.
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PMID:Antagonism of neutrophil adherence in the deteriorating stroke model in rabbits. 781 56

The protective effects of a novel dihydropyridine calcium antagonist with platelet-activating factor-antagonistic action, F-0401, on ischemic brain damage were investigated using experimental ischemia models in rats and gerbils. F-0401 (1 and 10 mg/kg, i.p.) prevented increases in water content, determined by the wet-dry method, in ischemic areas 24 hr after 1 hr of middle cerebral artery occlusion in the rat. Pretreatment with F-0401 (1 and 10 mg/kg, i.p.) prevented extravasation of Evans blue dye in the brain following 2 hr of bilateral carotid artery occlusion and 2 hr of reperfusion in the rat. Pretreatment with F-0401 (1 and 10 mg/kg, i.p.) protected against neuronal damage to hippocampal CA1 pyramidal cells following 3 and 5 min of forebrain ischemia in the gerbil. Immunostaining against microtubule-associated protein-2 also demonstrated preservation of CA1 neurons in F-0401-treated animals. Thus, this study shows that F-0401 prevents the occurrence of brain edema, disruption of blood-brain barrier and neuronal damage caused by cerebral ischemia. The results demonstrate that F-0401 may be a powerful candidate as a therapeutic agent in the treatment of acute stroke in man.
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PMID:Protective effects of a novel calcium antagonist with platelet-activating factor-antagonistic action, F-0401, against ischemic brain damage. 784 11

Regional cerebral blood flow (rCBF) and laser-Doppler perfusion were measured in rats after controlled cortical impact injury (CCII), a model of traumatic brain injury. Male Long-Evans rats were anesthetized with isoflurane and surgically prepared with arterial and venous cannulae. CCII was induced after a craniectomy by deforming the right parietal cortex to a depth of 2 mm with a metal cylinder traveling at a velocity of 5.2 m/s. Laser-Doppler perfusion was monitored from the surface of the left frontal cortex. rCBF, using 14C-isopropyliodoamphetamine, and laser-Doppler perfusion were measured in three groups of rats consisting of a sham group (n = 6), a group 30 min after CCII (n = 6), and a group 4 h after CCII (n = 5). CCII was characterized by cortical ischemia (rCBF < 20 mL.100 g-1.min-1) surrounding the site of impact. The occipital cortex, a cortical region distant from the impact site, was also ischemic in some, but not all, injured rats. In the 30-min group, the ischemic zone showed very sharp boundaries with cortical areas of hyperperfusion surrounding the ischemic zone. In the 4-h group, the ischemic boundaries were not as sharp and the hyperperfusion surrounding the ischemic zone was no longer present. The caudate-putamen, hippocampus, and thalamus showed significant reductions in rCBF ranging from 50% to 30% of control 30 min and 4 h postinjury, respectively. We conclude that complex changes in rCBF occur shortly after CCII and persist for at least 4 h. During this time several brain regions, especially the cortical areas, may suffer damage due to the ischemia.
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PMID:Regional cerebral blood flow after controlled cortical impact injury in rats. 789 19

Methanol is an ocular toxicant which causes visual dysfunction often leading to blindness after acute exposure. While the manifestation of the toxicity has been widely studied, the mechanism by which the injury is produced is still uncertain. A major unanswered question pertains to the site of action, i.e. direct retinotoxicity versus primary optic nerve toxicity with secondary retinotoxicity. In the present study, the effect of methanol on the oscillatory potentials (OPs) of the electroretinogram (ERG) were evaluated in acutely treated folate sufficient (FS) and folate reduced (FR) Long-Evans rats. The OP amplitudes of the acutely dosed FR rats displayed non-selective decreases in all OP amplitudes and non-selective increases in all OP latencies at methanol doses ranging from 1.5 to 3.0 g/kg. Comparing decreases of op2 and ERG b-wave amplitudes with blood formate concentration demonstrates that the b-wave is more sensitive than op2 in a blood formate concentration range of 6-14 mM, suggesting that retinal ischemia is not involved in methanol-induced visual system toxicity.
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PMID:Evaluation of methanol-induced retinotoxicity using oscillatory potential analysis. 797 8


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