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)

The aim of this study was to determine whether the formation of edema that occurs secondary to the neutrophil-dependent increase in microvascular permeability contributes to the genesis of no-reflow in postischemic skeletal muscle. To address this issue, four experimental approaches were used. In the first group, capillary perfusion was assessed in nonischemic canine gracilis muscles in which interstitial fluid volume was increased to a level similar to that in postischemic muscle. In the second and third groups, edema formation was prevented in postischemic skeletal muscles by administration of phalloidin or a hypertonic hyperosmotic saline-dextran solution (HSD; 7.5% saline-6% Dextran 70), and the extent of capillary no-reflow was assessed. In the final group of experiments, a monoclonal antibody (MAb) that binds to the common beta-subunit of the leukocyte integrin CD11/CD18 (MAb IB4) was administered after the development of postischemic edema, and capillary perfusion was determined. Formation of edema in nonischemic preparations and ischemia-reperfusion (I-R) were associated with marked reduction in the number of patent capillaries per fiber (1.2 +/- 0.1 and 0.4 +/- 0.1, respectively) compared with nonedematous nonischemic controls (2.5 +/- 0.3). Treatment with phalloidin or HSD prevented edema formation and attenuated the reduction in the number of patent capillaries per fiber (1.62 +/- 0.2 and 1.71 +/- 0.2, respectively) induced by I-R, whereas administration of MAb IB4 after the formation of edema in reperfused muscles failed to limit capillary no-reflow (0.5 +/- 0.1 patent capillaries/fiber).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Leukocyte adhesion, edema, and development of postischemic capillary no-reflow. 794 78

To monitor the ischemic and/or reperfusion injury after porta hepatis occlusion (Pringle maneuver) in livers subjected to hypotension, serum alanine amino transferase (ALT), liver malondialdehyde (MDA), and liver glutathione (GSH) levels were measured. MDA is a by-product of oxidant-induced lipid peroxidation, and GSH is an endogenous antioxidant. The effects of lactated Ringer's (LR) and hypertonic saline (7.5%)/Dextran (6%; HSD) resuscitation on liver injury, if any, was investigated. Rats in sham (S, n = 8) and five other groups (n = 8) underwent femoral artery and vein catheterization and laparotomy. The hemorrhage and ischemia (HI) group was bled 30% of their blood volume and had their porta hepatis occluded for 30 min. The HI, LR, and HSD groups underwent both hemorrhage and occlusion. Thirty minutes after hemorrhage, the LR and HSD groups received either LR (equivalent to three times the shed blood) or HSD (10 mL/kg) resuscitation over 30 min. Both LR and HSD resuscitation lowered the increased ALT and liver tissue MDA seen in the HI group. ALT was decreased from 348 +/- 93 IU/L in the HI group to 200 +/- 98 IU/L in the LR and 139 +/- 74 IU/L in the HSD groups. Liver tissue MDA was 353 +/- 22 nmol/g/tissue in the HI group and LR decreased it to 261 +/- 17 nmol/g/tissue, whereas HSD decreased it to 273 +/- 20 nmol/g/tissue. The decrease in ALT and the increase in liver GSH were more pronounced with HSD resuscitation (P < 0.05). HSD seems to be more effective than LR in decreasing the liver tissue damage produced by total hepatic inflow occlusion under hypovolemic conditions.
 ...
PMID:Hypertonic saline dextran alleviates hepatic injury in hypovolemic rats undergoing porta hepatis occlusion. 1268 52

Hypoxic-ischemic brain injury is a leading cause of neurodevelopmental morbidities in preterm and full-term infants. Blood-brain barrier dysfunction represents an important component of perinatal hypoxic-ischemic brain injury. The extracellular matrix (ECM) is a vital component of the blood-brain barrier. Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) are important ECM components. They contribute to brain development, blood-brain barrier maintenance, and to regenerative and repair processes after hypoxic-ischemic brain injury. We hypothesized that ischemia at different durations of reperfusion affects the ECM protein composition of MMPs and TIMPs in the cerebral cortex of fetal sheep. Cerebral cortical samples were snap-frozen from sham control fetuses at 127 days of gestation and from fetuses after exposure to 30-min carotid occlusion and 4-, 24-, and 48-h of reperfusion. Protein expression of MMP-2, -8, -9, and -13 and TIMP-1, -2, -3, and -4 was measured by Western immunoblotting along with the gelatinolytic activity of MMP-2 and MMP-9 by zymography. The expression of MMP-8 was increased (Kruskal-Wallis, p = 0.04) in fetuses 48 h after ischemia. In contrast, changes were not observed in the protein expression of MMP-2, -9, or -13. The gelatinolytic activity of pro-MMP-2 was increased (ANOVA, p = 0.02, Tukey HSD, p = 0.05) 24 h after ischemia. TIMP-1 and -3 expression levels were also higher (TIMP-1, ANOVA, p = 0.003, Tukey HSD, p = 0.01; TIMP-3, ANOVA, p = 0.006, Tukey HSD, p = 0.01) 24 h after ischemia compared with both the sham controls and with fetuses exposed to 4 h of reperfusion. The changes in the expression of TIMP-1, -2, and -3 correlated with the changes in the MMP-8 and -13 protein expression. We speculate that regulation of MMP-8, MMP-13, and TIMPs contributes to ECM remodeling after is chemic-reperfusion injury in the fetal brain.
 ...
PMID:Ischemic-Reperfusion Injury Increases Matrix Metalloproteinases and Tissue Metalloproteinase Inhibitors in Fetal Sheep Brain. 3004 80