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

The purpose of the present study was to clarify the effect of topical administration of a nitric oxide synthase inhibitor on extracellular glutamate concentration in transient forebrain ischemia. Two microdialysis probes were inserted into the bilateral striata of Wistar rats. NG-Nitro-L-arginine (L-NNA) with or without L-arginine was topically administered into the unilateral striatum through one of the microdialysis probes, while Ringer's solution was perfused into the contralateral striatum as the control, and 14 minutes of forebrain ischemia was applied. The extracellular glutamate concentration during ischemia and subsequent reperfusion was statistically significantly higher on the 100 microM L-NNA-perfused side than on the control side, but 1 mM L-NNA was ineffective. When 100 microM L-NNA was perfused together with 500 microM L-arginine, the glutamate concentration did not differ from that on the control side. Moreover, administration of 500 microM L-arginine significantly suppressed the glutamate elevation after reperfusion. The fact that the lower dose of L-NNA increased the accumulation of glutamate during ischemia and reperfusion without altering blood flow may indicate that nitric oxide affords protection against ischemia neuronal damage. However, since the higher dose of L-NNA did not affect the glutamate concentration, it appears that the effect of nitric oxide on extracellular glutamate concentration in forebrain ischemia differs, depending on the degree of the inhibition of NOS activity.
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PMID:Modulation of extracellular glutamate concentration by nitric oxide synthase inhibitor in rat transient forebrain ischemia. 895 19

An in vivo rat model of isolated intestinal ischemia-perfusion was developed. This is used to compare the effects of crosslinked hemoglobin (PolyHb) versus crosslinked hemolobin-superoxide dismutase-catalase (PolyHb-SOD-CAT) on free radical generation in ischemia-reperfusion. Fasted, anesthetized male Sprague Dawley rats underwent midline laparotomy with cannulation of the abdominal aorta and inferior vena cava. Ligation was carried out at the renal pedicles bilaterally and the aorta and vena cava proximally at the diaphragm and distally above the femoral bifurcation. The system was flushed of blood with 20 ml of lactated Ringer's solution. The portal vein was then cannulated with distal clamping at the porta hepatis so that isolated intestinal perfusion could be achieved with the aorta as the inlet and the portal vein as the outlet. Following a 90 minute ischemic time, perfusates containing modified hemoglobin (5 g/dl) and 4-hydroxybenzoate (5 mM) were infused at 0.8 ml/min for 10 min. Portal vein effluent samples were collected at 2.5 minute intervals. Hydroxyl radical generation was assessed by an aromatic hydroxylation technique with 4-hydroxybenzoate (4HB). Reaction of hydroxyl radical with 4HB produces 3,4 dihydroxybenzoate (3,4 DHBA). In the PolyHb group, the levels of 3,4-DHBA increased 10.75-13.58 x-fold above pre-perfusion values compared to 2.25-3.75 x-fold in PolyHb-SOD-CAT group. This indicates that PolyHb-SOD-CAT is effective in reducing in vivo hydroxyl radical generation following reperfusion. Since free radicals may play a major role in the pathogenesis of ischemia-reperfusion injury, this suggests a role for PolyHb-SOD-CAT as a possible protective perfusate in intestinal reperfusion injury.
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PMID:Crosslinked hemoglobin-superoxide dismutase-catalase scavenges free radicals in a rat model of intestinal ischemia-reperfusion injury. 908 38

Gut-origin sepsis is a serious medical complication of military injuries following hemorrhage. Splanchnic ischemia induces intestinal necrosis leading to systemic bacteremia. Rat and mouse models of hemorrhagic shock were used to investigate bacterial translocation from the gut. Orally administered ameliorative treatments using the cytokine interleukin-6 (IL-6) were able to reduce or eliminate sepsis following hemorrhage. To mimic battlefield wounds and hemorrhage, anesthetized mice were bled from the femoral artery, held at a mean arterial blood pressure of 35 mm Hg for 1 hour, and then resuscitated with shed blood and 2-fold volume lactated Ringer's solution. Anesthetized rats were bled from the carotid artery at a rate of 15 ml/kg at 1 ml/minute. Bacteriological cultures of livers and mesenteric lymph nodes from hemorrhaged animals given recombinant IL-6 had significantly fewer colonies per gram of tissue than saline-fed controls. 125I-labeled IL-6 remained in the gut for up to 6 hours giving regional protection, whereas labeled interleukin-2 was disseminated throughout the body in the same time. In vivo and vitro studies of IL-6 showed that long incubations with high doses of trypsin, chymotrypsin, or intestinal contents were necessary to inactivate the bioactivity of this cytokine. Electron microscopy showed that epithelial cells from hemorrhaged mice fed saline had sparse or missing villi and vacuolated cytoplasm. Epithelial cells from control mice or mice hemorrhaged and fed cytokine appeared completely normal. Oral administration of IL-6 on the battlefield may be an important treatment for the prevention of sepsis following hemorrhage.
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PMID:Systemic sepsis following hemorrhagic shock: alleviation with oral interleukin-6. 915 11

We examined the protective effect of diltiazem, a calcium antagonist, on myocardial ischemic injury associated with generation of hydroxyl free radicals (.OH). Salicylic acid in Ringer's solution (0.5 nmol.microliter-1.min-1) was infused directly through a microdialysis probe to detect the generation of .OH as reflected by the formation of 2,3-dihydroxybenzoic acid (DHBA) in the myocardium. Cardiac dialysate was assayed for 2,3-DHBA by a high-performance liquid chromatographic-electrochemical (HPLC-EC) procedure. The heart was subjected to myocardial ischemia for 15 min by occlusion of left anterior descending artery (LAD). The presence of .OH was indicated in the ischemic reperfused rat heart. However, when heart was reperfused, the elevation of 2,3-DHBA by 15-min ischemia was not observed in the ischemic zone following systemic administration of diltiazem (100 micrograms.min-1.kg-1), a calcium antagonist. When corresponding experiments were performed with allopurinol (10 mg.kg-1) administration of i.v. injection, the elevation of 2,3-DHBA was not observed. These results suggest that diltiazem may suppress the .OH generation from xanthine-xanthine oxidase system by ischemia-reperfusion.
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PMID:Protective effect of diltiazem on myocardial ischemic injury associated with .OH generation. 917 83

There is evidence that endothelin (ET) is involved in disturbances of the hepatic microcirculation after warm ischemia. In this study we investigated the influence of a mixed ETA-, ETB-receptor antagonist (Bosentan) on ischemia-reperfusion damage of the liver by means of intravital fluorescence microscopy (IVM). Clamping of the left liver lobe (= warm ischemia) was performed in 16 male Wistar rats for 70 min. The treatment group (N = 8) received 15 mg/kg Bosentan (Ro-47-0203) 1 min prior to reperfusion. Controls (N = 8) received an equivalent amount of Ringer's solution. Between 20 and 90 min after reperfusion, leukocyte-endothelial cell interactions in sinusoids and postsinusoidal venules as well as perfusion of hepatic acini were studied. Application of Bosentan improved sinusoidal blood flow, attenuated manifestations of microvascular perfusion failure, and decreased the number of rolling leukocytes in postsinusoidal venules. Our results provide further evidence that ET is involved in postischemic impairment of hepatic microhemodynamics during reperfusion.
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PMID:Effects of mixed ETA and ETB-receptor antagonist (Ro-47-0203) on hepatic microcirculation after warm ischemia. 920 Nov 1

We investigated serotonin as a parameter of cold and warm ischemic injury prior to transplantation. Lewis rats were used as both donors and recipients, and the proximal 20 cm of jejunum served as the graft. The grafts were preserved in 4 degrees C lactated Ringer's solution for 0, 6, 12, 18, and 24 hr after harvest for cold ischemia (n=7/group). The superior mesenteric artery was clamped for 0, 15, 30, 60, and 120 min before harvest for warm ischemia (n=7/group). The serotonin concentration was measured in the luminal effluent and the preservation solution before transplantation, and total serotonin was calculated as the sum of these amounts. Finally, transplantation was performed heterotopically. Total serotonin increased significantly with both cold and warm ischemic time (P<0.01 by analysis of variance, Fisher's PLSD); however, between 18 hr and 24 hr of cold ischemic time only, there were no significant changes. Total serotonin levels correlated well with cold and warm ischemic time, as shown by linear regression analysis (cold ischemia: R2=80.2%, P<0.01; warm ischemia: R2=92.8%, P<0.01). We established the cutoff level of total serotonin to predict the graft survival at 2200 ng, and using this critical level, graft survival was predicted by total serotonin with a sensitivity of 71.4% and a specificity of 89.8%. Immunohistochemical staining with the serotonin antibody revealed that the number of serotonin-positive cells decreased with both cold and warm ischemic time. In conclusion, serotonin is a useful parameter of cold and warm ischemic injury before transplantation and can assist in predicting graft survival.
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PMID:Serotonin as a useful parameter for cold and warm ischemic injury in small bowel transplantation. 927 3

In heart transplantation, global ischemia of a graft is followed by reperfusion injury. The formation of oxygen free radicals induces arrhythmias and impairs functional recovery of the graft. This study was executed to evaluate the effect of the new antioxidant, nitecapone, on ischemia-reperfusion injury in heart transplantation in rats. Donor hearts were perfused and stored at +4 degrees C for 2 h in either Ringer's solution in the control group (C-group, n = 26) or Ringer's solution with nitecapone (NC) added (NC-group, n = 18). The donor aorta was anastomosed to the recipient's abdominal aorta and the pulmonary artery to the recipient's inferior vena cava. The grafts were classified into three categories based on the functional recovery. The rats in both groups were killed at 10, 30, or 60 min after release of the aortic clamp. Tissue samples for chemiluminescence were obtained from the left ventricle, the right ventricle, and the septum of the heart. All grafts in the NC-group (18/18) began beating after release of the aortic clamp, whereas only 50% (13/26) of the grafts in the C-group recovered (P < 0.0004). Chemiluminescence analysis showed lipid peroxidation values to be higher in the C-group than the NC-group up to 1 h after reperfusion. Also, the right ventricle samples showed lower chemiluminescence values in the NC-group than in the C-group. In conclusion, our results do not support the theory that different regions of the heart have different vulnerability to ischemia-reperfusion injuries. Nitecapone has a beneficial effect on the preservation of the grafts in terms of functional recovery.
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PMID:Nitecapone is of benefit to functional performance in experimental heart transplantation. 940 81

The involvement of nitric oxide (NO) in the development of ischemic cytotoxic edema was investigated by inhibiting nitric oxide synthase (NOS) activity with N omega-nitro-L-arginine (NLA). Bilateral carotid artery occlusion (15 min) alone or with release (15 and 60 min) served as a model for edema induction. NLA, N omega-nitro-D-arginine methyl ester (D-NAME) or Ringer's solution were administered 4 hr prior to ischemia or sham operation. Treatment with a stable nitroxide radical, 4-hydroxy-2,2, 6,6-tetramethylpiperidine-L-oxyl (TPL), was used to assess free radical involvement in edema. Accumulation of tissue water was evaluated by measuring specific gravity (SG) of brain cortex and histological examination. There was a greater reduction of cortical SG in early reperfusion (15 min) and a lesser decrease in SG (60 min later) in NLA-than in D-NAME- or Ringer's-treated gerbils. The NLA effect was confirmed by histological examination of the brain tissue. TPL treatment (pre- and postischemic) ameliorated the formation of edema to the same degree as NLA. The findings indicate a biphasic NLA modulation of cytotoxic edema most likely mediated through absence or presence of NO-derived free radicals.
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PMID:The effect of nitric oxide inhibition on ischemic brain edema. 941 22

Lung injury often occurs after hepatoenteric ischemia, with xanthine oxidase (XO, an oxidant-generating enzyme), released from reperfusing liver and intestines, mediating a significant component of this injury. Since pentastarch administration decreases intestinal reperfusion injury, we determined whether resuscitation with PentaLyte (a pentastarch-containing solution) would decrease hepatoenteric reperfusion injury, xanthine oxidase release, and concomitant lung injury after aortic occlusion- reperfusion. Aortic occlusion was established in rabbits for 40 min, and was followed by 3 h of reperfusion, during which either PentaLyte or lactated Ringer's solution-based resuscitation was administered. Sham-operated animals served as controls. Hepatoenteric reperfusion injury, as manifested by release of the enzyme aspartate aminotransferase and decreased gastric intramucosal pH, was significantly (p < 0.0167) attenuated by PentaLyte administration after aortic occlusion-reperfusion, as compared with its occurrence in animals given lactated Ringer's solution. The release of XO after aortic occlusion-reperfusion was 4-fold smaller after PentaLyte administration than after resuscitation with lactated Ringer's solution (p < 0.05). Pulmonary injury, as defined by an increase in bronchoalveolar lavage fluid (BALF) protein content and lactate dehydrogenase (LDH) activity, was 4-fold less after PentaLyte administration following aortic occlusion-reperfusion than after administration of lactated Ringer's solution (p < 0.05). We conclude that remote pulmonary injury is significantly decreased by concomitant PentaLyte-mediated reduction of hepatoenteric reperfusion injury and XO release.
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PMID:PentaLyte decreases lung injury after aortic occlusion-reperfusion. 962 Sep 36

The effects of myocardial ischemia and reperfusion on interstitial hydroxyl radical production, in the left ventricular myocardium of anesthetized cats, were investigated. Ringer's solution containing salicylic acid was perfused through an implanted microdialysis probe. Hydroxyl radical production was evaluated as the 2,3 and 2,5 dihydroxybenzoic acid (DHBA) concentrations in the microdialysates by an on-line high performance liquid chromatography system. Myocardial ischemia for 60 min, induced by ligation of the left anterior descending coronary artery, significantly increased both 2,3 and 2,5 DHBA levels when compared with the sham-operated cats. Naloxone (1 mg/kg, bolus, intravenous), an endogenous opioid peptide receptor antagonist, significantly suppressed the ischemia-induced production of hydroxyl radicals. Myocardial ischemia also induced cardiac arrhythmia. Naloxone reduced the severity of ischemia-induced arrhythmia, as observed by a significantly lower arrhythmia score (1.4 +/- 0.2 vs. 4.6 +/- 0.4 for control), and by diminished incidence of ventricular tachycardia (0/7 vs. 8/8 for control) and ventricular fibrillation (0/7 vs. 3/8 for control). Furthermore, perfusion of dynorphin (0.25 microgram, 2.5 micrograms and 25 micrograms), an endogenous opioid peptide receptor agonist, increased hydroxyl radical production. Our results suggest that, in anesthetized cats, myocardial ischemia can induce production of interstitial hydroxyl radical in left ventricular myocardium, and this production may involve the actions of released endogenous opioid peptides on their receptors.
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PMID:Increased formation of interstitial hydroxyl radical following myocardial ischemia: possible relationship to endogenous opioid peptides. 975 28


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