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)

The effect of ischemia on the integrity of myocardial lysosomes was observed 3 1/2 and 24 hours after the production of infarcts in 20 anesthetized closed-chest dogs by electrically induced thrombosis of the left anterior descending coronary artery. Biopsies from normal, marginal and infarcted areas were fixed and incubated to localize the lysosomal enzymes acid phosphatase and aryl sulphatase. Reaction product in normal cells was localized in small circular or oblong profiles between bundles of myofilaments and adjacent to mitochondria. In addition, curvilinear, membrane-bound profiles containing reaction product were found in close apposition to transverse tubules and near the free margins of the myocardial cells. Thus the distribution of elements of the sarcoplasmic reticulum. Additional reaction product was also seen in residual bodies, on myelin figures, and in the few conventional appearing spherical lysosomes. Little or no acid phosphatase or aryl sulphatase reaction product was seen in the sarcoplasmic reticulum of infarcted myocardium. The degree of cellular degeneration correlated with disappearance of enzyme activity from the sarcoplasmic reticulum and included disruption of membranes and loss of mitochondrial matrix and erosion of I but not A bands. Marginal areas showed variable amounts of cellular degeneration. Separation of myofilament bundles and loss of glycogen correlated with the localized disappearance of acid phosphatase and aryl sulphatase activity in marginal tissue. Disruption of mitochondrial and erosion of I bands correlated with extensive loss of these enzymes. The data suggest that degeneration of myocardial cells following ischemic injury is associated with release of endogenous lysosomal enzymes from the sarcoplasmic reticulum.
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PMID:Cytochemical localization of lysosomal enzyme activity in normal and ischemic dog myocardium. 16 85

The role of lysosomal enzymes in ischemic retinal pigment epithelial cells (RPE) of albino rabbits was examined with the modified Gomori technique for acid phosphatase. Ischemia was produced by cutting the lateral posterior ciliary artery and short posterior ciliary arteries (PCA). Five days after PCA-cut RPE in the ischemic region were disorganized by increased enzymatic digestion. In RPE of the border between the ischemic and normal region a lot of fragmented outer segments were phagocytosed 24 h to 7 days after PCA-cut. At this time phagosomes appeared much more frequently than in the normal retina, showing several variations in their shape, localization, and histochemical reaction. However, after 10 and 14 days, RPE in the border had a tendency to reduce the phagocytic activity. A strong acid phosphatase activity was encountered in the phagosomes of macrophages, which was considered to be derived from RPE, and seemed to play the major role in scavenging destructed retinal elements.
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PMID:Phagocytic activity in the ischemic retinal pigment epithelial cells. An electronmicroscopic histochemical study of acid phosphatase. 30 84

The conducting system was studied in an in situ perfused swine heart preparation with reduced coronary flow (ischemia) using perfusate containing high and low levels of glucose (26.6 versus 8.6mM) with and without insulin. Coronary flow was maintained at normal levels for 60 minutes in control hearts. In ischemic hearts flow was reduced to about 50 percent of control levels for 30 minutes. Ultrastructural studies documented only subtle modifications of Purkinje fibers in ischemic hearts. Glycogen depletion and disruption of cell junctions were observed in some fibers. One consistent finding was the activation of the lysosomal system. The outer membranes of primary lysosomes appeared herniated and in some cases disrupted, and small vesicles containing hydrolytic enzymes were seen in association with the Golgi apparatus and larger primary lysosomes. Specimens prepared for the demonstration of acid phosphatase indicated a redistribution of hydrolytic enzymes in Purkinje fibers with a depostion of acid hydrolases in smaller lysosomal vesicles, the transverse and side-to-side junctions between cells, and occasionally in the sarcoplasmic reticulum. Enriched perfusate containing high levels of glucose with insulin appeared to have no therapeutic effects in terms of the structure of the Purkinje fibers. The results suggest that alterations in the lysosomal system may be one of the earliest structural changes which occur in oxygen-deficient hearts.
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PMID:Ischemic injury to the conducting system of the heart. Involvement of myocardial lysosomes. 43 Oct 98

Occlusion of the circumflex coronary artery induced a profound redistribution in ischemic rabbit myocardium of several lysosomal acid hydrolases, including cathepsin D, B-acetylglycosaminidase, and acid phosphatase. 30-45 min after ligation non-sedimentable cathepsin D activity rose from 36% of the total activity to 42-48%, and in immunohistochemical preparations cathepsin D appeared to have diffused from lysosomes into the cytosol of injured cells. A pharmacologic dose of methylprednisolone (50mg/kg) significantly delayed the subcellular redistribution of cathepsin D and the other hydrolases in ischemic heart. Thus, in treated hearts the nonsedimentable activity of cathepsin D rose to only 38% after 30 min of ischemia and 42% after 45 min (P is less than 0.05 compared to untreated ischemia at each time). Similarly, unlike untreated hearts, noevidence of enzyme diffusion from lysosomes could be demonstrated immunohistochemically in corticosteroid-treated ischemic hearts for over 45 min. After 1-2 h of ischemia, however, steroid-protected myocytes deteriorated and the biochemical activity and anatomical distribution of cathepsin D were indistinguishable from untreated ischemic hearts. This study demonstrates that corticosteroid pretreatment does not prevent alterations in cardiac lysosomes during severe ischemia indefinitely, but does delay their development significantly.
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PMID:Influence of methylprednisolone of the sequential redistribution of cathepsin D and other lysosomal enzymes during myocardial ischemia in rabbits. 70 78

The pathobiology of the process of myocardial injury during ischemia comprises a series of events that results in the release of lysosomal enzymes from their subcellular locations within the myocardium. We have developed a canine model of acute myocardial ischemia in which the anterior descending coronary artery is ligated, myocardial blood flow is measured using radioactive microspheres, and tissues from subendocardium and subepicardium are assayed for activity of lysosomal hydrolases:N-acetyl-beta-glucosaminidase (NAG), beta-glucuronidase (beta-gluc), and acid phosphatase (AP). Particulate fractions of subendocardium revealed significant depletion of of total acid hydrolases (NAG, beta-gluc, and AP) after one and two hours of ischemia. In addition, after two hours of ischemia, the total activity of these three hydrolases in the subendocardial supernatant was decreased, correlating significantly with diminished myocardial blood flow (NAG: r =0.96; beta-gluc: r = 0.95; AP: r = 0.75). The diminished enzymatic levels in thesupernatant suggested "washout" of the hydrolases that was more efficient in those ischemic areas that had higher myocardial flow (greater than 20% of control). These changes in distribution of lysosomal hydrolases indicate early involvement of these enzymes in the pathobiology of myocardial injury and demonstrate the dynamic relationship of "washout" of acid hydrolases with the degree of diminished blood flow.
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PMID:Release of lysosomal enzymes during ischemic injury of canine myocardium. 103 97

Early changes in lysosomal enzymes must occur if their role is significant in irreversible myocardial injury. Therefore, we ligated the anterior descending coronary artery in 14 dogs and after 60 min excised epicardial and endocardial samples from the ischemic and adjacent normal heart. The collateral flow measured with radioactive microspheres in the endocardial samples averaged 19% of control. The muscle was disrupted and fractionated by ultracentrifugation into nuclear pellet (NP), heavy lysosomal pellet (HL), light lysosomal pellet (LL), microsomal pellet (M) and supernate (S). Electron microscopy demonstrated changes characteristic of sichemia in whole tissues and sedimented fractions. Acid phosphatase reaction product was present in residual bodies in the HL fraction and membrane-bound vesicles in the LL fraction and in the intact tissue. Significant decreases in the specific activity of N-acetyl-beta-glucosaminidase and beta-glucuronidase occurred in the endocardial LL fraction, while significant increases in both were found in the ts fraction (P less than 0.05). Losses of acid phosphatase occurred in both LL and S fractions. Moreover, decreases of total N-acetyl-beta-glucosaminidase in the HL fraction and of total beta-glucuronidase and acid phosphatase in the LL fraction were positively correlated (P less than 0.01) with the degree of ischemia measured with radioactive microspheres. Only insignificant enzymatic changes were found when the collateral flow was greater than 40%, and the differences were less significant in epicardial samples where the flow averaged 29%. The early loss of enzymes from the lysosomal fractions in severe ischemia suggests a role for lysosomal hydrolases in the necrosis that follows coronary occlusion.
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PMID:Effect of collateral flow on epicardial and endocardial lysosomal hydrolases in acute myocardial ischemia. 115 94

Myocardial biochemical systems which are sensitive to hypoxic and ischemic insult were studied to determine the possible etiology of ventricular endocardial hemorrhage in miniature swine following +GZ stress. Unanesthetized animals were subjected to a single, 120-s +9 GZ acceleration. Approximately 1-2 h following +GZ exposure, the animals were anesthetized and the hearts removed for analyses. Acceleration exposure resulted in the loss of acid phosphatase enzyme activity from the membrane-bound lysosomal fraction with concomitant increased activity in the soluble fraction. This suggests that lysosomal membrane integrity had been disrupted. Mitochondrial preparations from +GZ-stressed hearts exhibited marked increases in active respiratory rate and rate of calcium transport while oxidative phosphorylation efficiency was unchanged. The results clearly indicate that +GZ acceleration is capable of altering myocardial biochemical systems. However, the results tend to suggest that these alterations in cellular processes may be mediated by influences other than hypoxia or ischemia.
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PMID:Heart biochemical responses in miniature swine subjected to +Gz acceleration. 121 43

The right medial cerebral artery of 25 primates (Macaca radiata) was occluded transorbitally with an atraumatic clip. The time courses of infarct volume and capillary morphometric changes in the ischemic lenticular nucleus, caudate nucleus and insular cortex were then determined. Volume changes of ischemic foci were studied morphometrically using an enzyme histotopochemical acid phosphatase stain. During the first 4 hours extension (or spread) of the ischemic area was small and constant. Over the next hours, the ischemic focus increased in volume, becoming maximal in the lenticular nucleus in 24 hours and in the caudate nucleus in 48 hours. In the lenticular nucleus, edema developed 4 hours after onset of ischemia and was characterized by a decrease in capillary diameter and an increase in mean intercapillary distance. In the caudate nucleus and insular cortex, in the first hours after clipping the medial cerebral artery, capillary diameter and volume increased and intercapillary distance decreased. The data demonstrate that the therapeutic window of brain infarct treatment is during the first 4-6 hours after occlusion of the medial cerebral artery.
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PMID:Histochemical and morphometric investigation of the pathogenesis of acute brain infarction in primates. 158 89

The interrelation between intracellular cAMP content and activity of lysosomal hydrolases was studied in rat liver and heart during ischemia of varying genesis and after recirculation. The activity of acid phosphatase (AP) and cathepsin D (CD) was determined in the fraction enriched with lysosomes (FEL) and in the supernatant fraction (SF) at 30,000 x g. Ischemia of isolated perfused heart of 20 to 60 min as described by Langendorff was accompanied by an increase in the SF/FEL ratio. Postischemic reperfusion resulted in a further increase in this ratio. In a terminal state induced by cardiac arrest of 10 min and within the first postresuscitation hours the SF/FEL ratio in the rat liver also increased. Processing of the liver FEL with 0.025% concentration of detergent Triton X-100 was also indicative of lability of lysosomal membranes during recirculation. The intracellular cAMP content changed differently. During ischemia of the myocardium, the cAMP level rose by 40 min and remained increased after 20 and 40 min of reperfusion. The cAMP content in the liver decreased after 10 min of circulatory arrest and increased in the postresuscitation period achieving its peak 4 h after resuscitation. Intra-abdominal injection of lyposomes with incapsulated cAMP to rats in the postresuscitation period and the study of the effect of dibutyryl-cAMP, caffeine and isoproterenol on the activity of acid hydrolases of ischemic heart and after postischemic reperfusion showed that an increase in the cAMP content achieved in various ways was conducive to stabilization of lysosomal membranes.
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PMID:Role of cAMP in regulation of activity of acid hydrolases of rat heart and liver during ischemia and after recirculation. 166 65

Extracellular concentrations of ascorbic acid, glutathione, cysteine, uric acid, tyrosine, and tryptophan were monitored using intracerebral microdialysis in the left frontoparietal cortex of spontaneous hypertensive rats before, and for 3 h after, either focal ischemia [left middle cerebral artery occlusion (MCAO)] or sham operation. The size of the ischemic area and the position of the microdialysis probe were checked using the enzyme histotopochemical acid phosphatase reaction. The probe was always located in the cortex inside the stained area. Ascorbic acid levels rose immediately after MCAO and remained at about 12-fold for 3 h. There was a transient release of glutathione during 1-1.5 h. Uric acid concentrations were also increased but the differences did not reach significance. The levels of the amino acids tyrosine and tryptophan increased steadily after MCAO. The increases in cysteine were variable but significant. In some experiments, the pH of the dialysate was measured online. The parameters ascorbic acid, glutathione, cysteine, and pH are suitable for the early detection of cortical ischemic events by microdialysis.
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PMID:Extracellular antioxidants and amino acids in the cortex of the rat: monitoring by microdialysis of early ischemic changes. 172 46


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