Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Involvement of neuroexcitatory mechanisms in cerebral ischemia and brain injury was explored in experimental models of repetitive forebrain ischemia by temporary occlusion of carotid arteries in gerbils and cryogenic injury to the cerebral cortex in rats and gerbils. Our observations in these models revealed a pattern of injury that involved some anatomic structures outside the areas of direct ischemic or traumatic insult. Such foci of injury revealed conspicuously abnormal uptake of 45Ca associated with slight or moderate neuronal alteration, whereas severely injured areas showed no 45Ca uptake. Electron microscopic observations revealed a characteristic presence of calcium in swollen dendrites, closely resembling pictures obtained in neuroexcitatory conditions such as epileptic seizures. Abnormal uptake of 45Ca was associated with apparent blood-brain barrier changes characterized by intracytoplasmic uptake of extravasated albumin into the neurons. Protein synthesis assayed by in vivo [3H]leucine incorporation was reduced in regions showing calcium accumulation. Our observations suggest that neuroexcitation may play an important role in development of secondary and chronic changes after ischemic or traumatic brain insults.
 ...
PMID:Putative neuroexcitation in cerebral ischemia and brain injury. 223 87

To determine whether myocardial contrast echocardiography is quantitatively reproducible, repeated intracoronary injections of sonicated albumin (5%) were performed in eight open chest dogs. Paired injections were performed at baseline, during ischemia produced by ligation of a coronary artery, and during hyperemia induced by intravenous infusion of 0.75 mg/kg body weight of dipyridamole. Contrast washout curves were generated for the left anterior descending coronary artery territory (ischemic area) and left circumflex coronary artery territory (nonischemic area) by beat per beat analysis of frozen end-diastolic frames of left ventricular short-axis views. Peak contrast intensity, contrast washout half-time and area under the curve were derived from these curves. A total of 75 contrast washout curves were analyzed for the study of interinjection, intraobserver and interobserver reproducibility. The correlation coefficients between measurements obtained from paired injections of the echocardiographic contrast agent (interinjection reproducibility) ranged from 0.78 for peak contrast intensity to 0.87 for area under the curve. Percent error varied between 14.7% and 24.7%. The intraobserver variability in measurements was less than the interinjection variability, with a cumulative mean percent error of 17.8% and correlation coefficients of 0.72 (peak contrast intensity), 0.95 (area under the curve) and 0.96 (washout half-time). Interobserver correlation for all indexes was high (r = 0.92 to 0.96). It is concluded that peak contrast intensity, contrast washout half-time and the area under the curve derived from myocardial contrast washout curves can be measured reproducibly from videotapes. In addition, the variability between two injections attempted under identical conditions is greater than reader variability from videotapes.
 ...
PMID:Reproducibility of quantitative myocardial contrast echocardiography. 230 31

Primary graft failure and vascular thromboses are frequent complications of liver transplantation, yet the mechanisms responsible remain unclear. Previous work from our laboratory has shown that hepatic reperfusion injury results in damage at the microvessel level. The present study was performed to determine whether an increased susceptibility of immature animals to microvascular injury during reperfusion might be a contributing factor in these complications. Suckling (35 to 50 g) or adult (250 to 400 g) rats were subjected to 30 or 60 minutes of hepatic ischemia to the left and median lobes followed by 90 minutes of reperfusion. Control animals were sham-operated, time-matched rats. At the end of reperfusion, fluorescein-labeled albumin was injected systemically to mark perfused sinusoids. Frozen sections of liver biopsies were viewed under fluorescence microscopy. The perfused sinusoid density was determined by point count analysis and expressed as the number of intersections of perfused sinusoids with 25 randomly oriented points superimposed on the sinusoid field. In sham-operated rats, at both 30 and 60 minutes, there were no differences between sucklings and adults. After 30 minutes of ischemia and 90 minutes of reperfusion, adults showed a significantly decreased density of perfused sinusoids (4.5 +/- 0.1 intersections per field) when compared with suckling rats (6.0 +/- 0.3 intersections per field, P less than .001). However, in rats subjected to 60 minutes of ischemia followed by 90 minutes of reperfusion, the microvascular injury was more severe in suckling rats (2.7 +/- 0.2 intersections per field) than in adults (4.7 +/- 0.2 intersections per field, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Susceptibility of hepatic microcirculation to reperfusion injury: a comparison of adult and suckling rats. 230 90

The large mass of fixed macrophages resident in the liver make it a potentially rich source of cytokines. We have previously demonstrated that an isolated and severe ischemia/reperfusion injury to the liver results in cytokine release, specifically tumor necrosis factor alpha, and that TNF is then involved in the development of pulmonary pathology. This study was designed to determine the kinetics of TNF release following varying periods of hepatic ischemia and to further investigate the acute lung injury that follows. Suprahepatic blood samples were obtained at serial time points following a 45-, 60-, 75-, or 90-min ischemic insult to a segment of the rat liver with subsequent reperfusion. Using a bioassay based on the WEHI 164 cell line, plasma TNF levels were measured in all experimental animals; sham-operated control animals had undetectable levels. Changes in pulmonary capillary permeability were then measured using a standard 125I-labeled albumin washout technique following a 90-min ischemic insult with subsequent reperfusion. A significant increase in the mean permeability index was observed 9 to 12 hr following hepatic reperfusion (.601 +/- 102 as compared with .114 +/- .085 in sham-operated controls, P less than 0.005). Animals treated with anti-TNF antiserum prior to the induction of hepatic ischemia had a significantly reduced pulmonary capillary leak compared to animals pretreated with rabbit serum without TNF-blocking properties (.184 +/- .029 versus .694 +/- 052 for the control serum, P less than 0.005). TNF release follows both moderate and severe ischemic injury to the liver and the results reported here implicate TNF as an important mediator of increased pulmonary capillary permeability. These experiments confirm previous histologic studies that demonstrated pulmonary edema and intra-alveolar hemorrhage following hepatic ischemia/reperfusion, with subsequent blockade of the histologic injury by pretreatment with anti-TNF antiserum.
 ...
PMID:The production of tumor necrosis factor alpha and the development of a pulmonary capillary injury following hepatic ischemia/reperfusion. 230 55

Ischemia followed by reflow often results in tissue injury. Although reactive oxygens seem to play an important role in the pathogenesis of postischemic reflow-induced tissue injury, the mechanism and an efficient way to inhibit oxidative injury are not known. We studied the mechanism by which hepatic transport function was inhibited by a transient occlusion followed by reflow of the portal vein and hepatic artery by using a superoxide dismutase (SOD) derivative (SM-SOD) which circulates bound to albumin with a half-life of 6 h. Occlusion of the hepatic vessels for 20 min followed by reflow for 60 min significantly inhibited transhepatic transport of cholephilic ligands, such as bromosulfophthalein (BSP) and taurocholic acid. Intravenous administration of SM-SOD markedly inhibited the reflow-induced decrease in transhepatic transport of these ligands. Thiobarbituric acid - reactive metabolites (TBAR) in the liver and plasma remained unchanged during occlusion and reflow, while TBAR in the bile increased significantly. Intravenous injection of SM-SOD inhibited the reflow-induced increase in biliary TBAR. Xanthine oxidase activity in plasma also increased during occlusion and reflow by an SM-SOD-inhibitable mechanism. Polymorphonuclear leukocyte-dependent chemiluminescence of the peripheral blood remained unchanged during occlusion, but increased markedly with time after reflow. SM-SOD also inhibited the increase in chemiluminescence almost completely. These and other results suggested that the superoxide radical and/or its metabolite(s) might play an important role in the pathogenesis of the reflow-induced liver injury and that SM-SOD might be useful for studying the mechanism for tissue injury caused by oxygen toxicity.
 ...
PMID:Inhibition of ischemia and reflow-induced liver injury by an SOD derivative that circulates bound to albumin. 230 17

Myofiber injury-repair was studied in the rat following blunt trauma to the lower leg in order to understand how the inflammatory and regenerative responses of muscles are altered when myofiber rupture is accompanied by bleeding and clotting reactions. A contusion injury to the muscles of the lower hindlimb of the rat was induced by applying an impact force of 4.7 N-m/cm2 to one leg. The gastrocnemius and soleus muscles were removed bilaterally and evaluated by histochemical and immunohistochemical techniques to document myofiber, vascular, and connective tissue alterations for several days following insult (6-120 hr). A significant increase in wet weight of the gastrocnemius muscle was noted 24 hr postinjury as fluid accumulation and bruising were evident in the muscles resulting from bleeding and inflammation. Vascular disruption was confirmed by the localization of some plasma constituents (fibrinogen, albumin, and complement C3) throughout the interstitial space and even inside some of the damaged myofibers. Inflammation was present and persisted for 5 days as evidenced by continued mast cell degranulation and increased vascular permeability. Using antibodies to identify specific proteoglycans which appear or disappear at various times during muscle regeneration, muscle repair could be followed. The repair process required approximately 10 days for restoration of morphologically intact myofibers. Thus, myofiber repair processes appear to be maintained even after disruption of the vascular system and ischemia following blunt trauma.
 ...
PMID:Extracellular matrix changes following blunt trauma to rat skeletal muscles. 230 15

Ischemia-reperfusion lung injury limits lung transplantation. Neutrophil activation and/or xanthine oxidase-mediated purine degradation may cause toxic oxygen metabolite production and lung injury. We investigated whether circulating blood elements are involved in the pathogenesis of ischemia-reperfusion lung injury. Isolated rat lungs were perfused with physiological salt solution (PSS) stabilized with Ficoll until circulating blood elements were not detected in the lung effluent. Lungs were then rendered ischemic by stopping ventilation and perfusion for 45 min at room temperature. Lung injury occurred and was quantitated by the accumulation of 125I-bovine serum albumin into lung parenchyma and alveolar lavage fluid during reperfusion. Lung injury occurred, in the absence of circulating blood elements, when ischemic lungs were reperfused with PSS-Ficoll solution alone. Reperfusion with whole blood or PSS-Ficoll supplemented with human or rat neutrophils did not increase lung injury. Furthermore, during lung ischemia, the presence of neutrophils did not enhance injury. Experiments using PSS-albumin perfusate and quantitating lung injury by permeability-surface area product yielded similar results. Microvascular pressures were not different and could not account for the results. Toxic O2 metabolites were involved in the injury because addition of erythrocytes or catalase to the perfusate attenuated the injury. Thus reperfusion after lung ischemia causes injury that is dependent on a nonneutrophil source of toxic O2 metabolites.
 ...
PMID:Neutrophils are not necessary for induction of ischemia-reperfusion lung injury. 231 80

Coronary vascular osmotic reflection coefficients (sigma dS) for total protein, albumin (Alb), immunoglobulin (Ig)G, and IgM were determined in the anesthetized dog. Myocardial lymph was collected from the anterior interventricular lymphatic trunk, and the sigma dS estimated from filtration rate-independent lymph-to-plasma protein concentration ratios (CL/CPS). Lymph flows of at least 12 times base line were needed to produce filtration rate-independent CL/CPS, and these were achieved in 9 of 12 experiments. In these nine experiments, sigma dS for total protein, Alb, IgG, and IgM were, respectively, 0.67 +/- 0.02 (SE), 0.59 +/- 0.05, 0.70 +/- 0.03, and 0.87 +/- 0.01. The data were fitted to a model that showed that transvascular fluid and solute flux could be described by two populations of pores. A large pore system with an equivalent radius of 235 A was responsible for 39% of the transvascular volume flow. A small pore system less than 53 A accounted for the remaining flow. In a second group of experiments (n = 8), 60 min of ischemia decreased the sigma dS to 0.27 +/- 0.03, 0.07 +/- 0.05, 0.22 +/- 0.03, and 0.69 +/- 0.04 for total protein, Alb, IgG, and IgM, respectively. A single population of pores of 220 A could describe the entire transvascular volume flow. These results indicate that coronary vascular protein permeability is moderately high and can be increased significantly by ischemia.
 ...
PMID:Macromolecular transport in canine coronary microvasculature. 231 90

Hydrogen peroxide (H2O2) has been implicated in cardiac damage due to ischemia and reperfusion. We adapted an electron microscopic, histochemical method for demonstrating H2O2 produced by isolated cells to isolated, buffer-perfused rabbit hearts. The method involves formation of an electron-dense precipitate when H2O2 reacts with cerium chloride (CeCl3). We perfused hearts retrograde via the aorta with well-oxygenated bicarbonate-buffered solution, followed by one in which bicarbonate was replaced with imidazole (IPSS) to prevent precipitation of bicarbonate and CeCl3. Some hearts were made globally ischemic (30 min, 37 degrees C), reperfused 5 min with well-oxygenated IPSS containing 1 mM CeCl3, then processed for electron microscopy. Others were perfused with IPSS containing catalase (300 U/ml) or albumin before ischemia and upon reperfusion, followed by CeCl3 administration. Nonischemic control hearts perfused with IPSS (+/- catalase) were also studied. Electron micrographs were assessed visually and by computer for precipitate localization and amount. There was abundant precipitate on the luminal face of the coronary vascular endothelium in ischemic-reperfused, cerium-treated hearts, including those treated with albumin. There was significantly less in reperfused catalase-treated or nonischemic control hearts. X-ray microbeam analysis of the endothelial precipitate indicated the presence of Ce. This appears to be the first visual demonstration of a CeCl3-H2O2-dependent reaction product in intact isolated ischemic hearts. The data indicate that at the time of reperfusion some H2O2 is accessible to the vascular space, and that its amount can be reduced by perfused catalase. Further modifications this technique may be useful for assessing the sites and pathways by which H2O2 is generated by hearts or other buffer-perfused organs subjected to stresses such as ischemia or hypoxia.
 ...
PMID:Cerium chloride as a histochemical marker of hydrogen peroxide in reperfused ischemic hearts. 232 33

The influence of neutrophils on peritubular capillary permeability and intravascular red blood cell (RBC) aggregation after renal ischemia was studied in anesthetized Sprague-Dawley rats. Intraperitoneal administration of antineutrophil serum (ANS) reduced the number of neutrophils in the blood to 3% of normal. The control group received an equal volume of inactive serum. Renal macromolecular capillary permeability was studied from 1) extravasation of albumin and 2) plasma to lymph transport of plasma proteins and of neutral and negatively charged lactate dehydrogenase (LDH). The net driving force (NDF) for fluid transfer over the peritubular capillary membrane was determined by the micropuncture technique. The intrarenal distributions of neutrophils and RBC were measured by a histochemical method and 51Cr-labeled RBC, respectively. Under preischemic control conditions neither macromolecular permeability nor renal clearance of inulin was affected by ANS. However, the steep increase in the macromolecular transport from plasma to lymph resulting from 45 min of ischemia and reperfusion was blunted by ANS, and preischemic control values were restored after 1 h of recirculation. In the control group the mass transport of plasma proteins increased twofold and that of both neutral and negatively charged LDH fourfold. NDF was equal in the two groups. In the ANS-treated animals the intrarenal neutrophil content was only 2% of the control. Neutrophils were found mainly in the cortex, whereas RBC aggregation was observed only in the renal medulla. It is concluded that neutrophils mediate postischemic capillary leakage. It is suggested that this leakage underlies RBC aggregation and incomplete return of blood flow in the renal medulla after ischemia.
 ...
PMID:Peritubular capillary permeability and intravascular RBC aggregation after ischemia: effects of neutrophils. 233 Sep 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>