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

This quantitative in vivo fluorescence microscopy study investigated the impact of warm versus cold Ringer's lactate (RL) graft rinse on various microvascular manifestations of ischemia-reperfusion injury after liver transplantation in the rat. Syngeneic orthotopic liver transplantation, including arterial revascularization, was performed in male Lewis rats following 24 h of cold storage in University of Wisconsin (UW) solution. In one group (n = 8) liver grafts were rinsed with 4 degrees C (cold) RL, whereas in the other group (n = 8) grafts were rinsed with 37 degrees C (warm) RL immediately prior to revascularization. Hepatic microvascular perfusion, leukocyteendothelium interaction, and Kupffer cell activation were quantified 30-90 min after graft reperfusion by direct visualization with intravital fluorescence microscopy. Moreover, biliary excretory graft function was analyzed by determination of bile flow and bile salt excretion during the first 90 min after reperfusion. Compared to grafts rinsed with cold RL, acinar and sinusoidal perfusion were found to be significantly increased after rinsing the grafts with warm RL. The amount of nonperfused acini declined from 18.1% +/- 4.0% to 7.4% +/- 1.6% (P < 0.05), and the total percentage of perfused sinusoids increased from 80.1 +/- 1.4 to 88.4 +/- 1.2 (P < 0.001) after cold and warm rinse, respectively. After rinsing the graft with warm RL, WBC adherence in sinusoids and especially in postsinusoidal venules decreased significantly by 28% (P < 0.001) and 33% (P < 0.001), respectively. Kupffer cell activation was markedly reduced after rinsing with RL at 37 degrees C, as indicated by a decelerated adherence of latex particles injected 80 min after reperfusion. Excretory graft function was dramatically increased following warm RL rinse during the 90-min observation period. Bile flow was enhanced from 1.04 +/- 0.5 to 3.9 +/- 0.8 ml/100 g liver per 90 min (P < 0.01), with a parallel rise in bile salt excretion from 24.3 +/- 5.8 to 128.0 +/- 19.8 mmol/ 100 g liver per 90 min (P < 0.05) when compared to cold RL. These data strongly suggest that rinsing liver grafts with warm RL prior to reperfusion represents a simple and inexpensive way to reduce the incidence of primary graft failure secondary to ischemia and reperfusion injury in liver transplantation.
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PMID:Intravital studies on beneficial effects of warm Ringer's lactate rinse in liver transplantation. 887 88

Activity of xanthine oxidoreductase (total xanthine dehydrogenase plus xanthine oxidase) and xanthine oxidase was determined cytophotometrically in periportal and pericentral areas of livers of rats under various (patho)physiological conditions that are known to affect the content of reduced glutathione. For this purpose, rats were either normally fed or fasted for 24 hours, fasted for 24 hours, and treated with diethylmaleate that depleted glutathione or treated by in vivo ischemia for 2 hours in the livers. Xanthine oxidoreductase activity was shown histochemically with the use of a tetrazolium salt procedure, and xanthine oxidase activity was localized with a cerium-diaminobenzidine-cobalt-hydrogen peroxide technique in unfixed cryostat sections of the livers. Cytophotometric measurements showed that total xanthine oxidoreductase activity was decreased after fasting and ischemia, whereas only ischemia caused reduced xanthine oxidase activity. Moreover, the percentage of xanthine oxidase of total xanthine oxidoreductase activity was constant in both periportal and pericentral areas at the level of approximately 4% in normally fed and 24-hour fasted and diethylmaleate-treated rats. Ischemia reduced this percentage in both areas of the liver to 2%. It was concluded that the amount of endogenous reduced glutathione did not affect the percentage of xanthine oxidase. The low percentage of xanthine oxidase as determined in the present in situ histochemical study indicates that in vivo the percentage oxidase in rat liver is lower than is assumed on the basis of biochemical assays in liver homogenates even after strictly controlled homogenization procedures. Apparently, conversion of xanthine dehydrogenase into xanthine oxidase may occur in vitro to yield percentages of xanthine oxidase of 10%-20% as are reported in the literature. The latter increase in the percentage of xanthine oxidase may be caused by changes in the local environment of the enzymes, which is left completely intact in histochemical assays. The finding of this low percentage of xanthine oxidase further stresses that the main function of xanthine oxidoreductase in the liver is not the production of superoxide anion radicals and/or hydrogen peroxide but rather the metabolism of xanthine to uric acid, which can act as a potent antioxidant.
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PMID:The proportion of xanthine oxidase activity of total xanthine oxidoreductase activity in situ remains constant in rat liver under various (patho)physiological conditions. 890 95

In order to determine whether treatment of animals with an n-3 fatty acid, eicosapentaenoic acid (EPA), could modify renal hemodynamics and physiology after normothermic ischemia, we studied 42 Spraque Dawley rats orally supplemented with either olive oil or a purified lysine salt of EPA for 4 weeks. Four experimental groups were established. Three groups were treated with increasing doses of EPA: 20 mg/kg per day (EPA 20), 40 mg/kg per day (EPA 40) and 80 mg/kg per day (EPA 80), and one group was supplemented with isovolumetric olive oil (OLI). A control group that received neither EPA nor ischemia was also studied. On day 28, right nephrectomy was performed, followed by 30 min of left renal warm ischemia. Basal arterial pressure and renal blood flow (RBF) were monitored in two kidneys before arterial occlusion and continuously thereafter throughout the experiment in one kidney using an electronic transducer and a flowmeter. From 60 to 120 min after the end of ischemia, urine output (microliter/min), glomerular filtration rate (GFR, microliter/min), measured by inulin clearance, and fractional reabsortion of sodium (FRNa) were determined every 20 min. Renal plasma flow (RPF, ml/min) and renal vascular resistance (VR, mm Hg/ml per min) were calculated. RPF was estimated as RBF (1-hematocrit). Before ischemia, the mean RPF and RBF were higher in EPA-fed than in olive oil-fed animals and after ischemia showed a significantly greater increase in EPA-fed animals than in olive oil-fed animals. Mean VR was lower in EPA-fed animals than in olive oil-fed animals, both before arterial occlusion and after ischemia. Mean urine output was similar in the OLI and EPA 20 groups, and significantly higher in the EPA 40 and EPA 80 groups than in the control group. GFR was significantly lower in the OLI and EPA 20 groups than in the control group. Finally, the EPA 40 group showed a similar and the EPA 80 group a slightly higher GFR than the control group. We conclude that EPA supplementation provides protection from renal ischemic-reperfusion injury, and this effect is more evident at higher EPA doses.
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PMID:Changes in renal hemodynamics and physiology after normothermic ischemia in animals supplemented with eicosapentaenoic acid. 895 85

The purpose of this study was to develop a primate model for assessing EEG, behavior and histology, and to test the effect of NMDA receptor blockade in transient focal ischemia. Squirrel monkeys (Saimiri sciureus) under halothane anesthesia were subjected to 110 min of transient focal ischemia (n = 15) by temporary clip occlusion of the MCA. An eight-lead EEG was recorded. Neurobehavioral testing was done in a subgroup of animals (n = 6). Brain temperature (37.5 degrees C) was monitored and controlled to avoid hypothermia or intergroup temperature differences, and blood pressure was regulated to 60 mmHg. The entire brain was subserially sectioned, and 52 standardized coronal sections encompassing the infarct were examined histologically 2 wk after the ischemia. Animals were randomized to receive either (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) 1 mg/kg of maleate salt or carrier solution, 20 min and again at 12 h after the onset of ischemia. Cingulate and retrosplenial cortex were examined for NMDA-antagonist-induced neuronal necrosis. No reduction, or trend toward reduction of neurobehavioral deficit was seen with MK-801. MCA occulsion reduced EEG power over the ischemic hemisphere. MK-801 appeared to cause brain activation, and globally increased power at several frequencies. MK-801 did not reduce infarction in either neocortex (p > 0.05) or striatum (p > 0.05). No selective neuronal necrosis was seen in the cingulate or retrosplenial cortex. We conclude that MK-801 given 20 min after the onset of transient ischemia offers no significant neuroprotective effect against either neurobehavioral deficit or ischemic infarction in this model of transient focal ischemia. Further experiments in unanesthetized animals are necessary to determine if MK-801-induced necrosis exists in the gyrencephalic brain, but the enhancement of primate brain electrical activity by MK-801 suggests that brain activation occurs in primates as it does in rodents.
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PMID:Postischemic therapy with MK-801 (dizocilpine) in a primate model of transient focal brain ischemia. 897 96

Hyponatremia is a common neuromedical problem seen in survivors of central nervous system injury. The etiology of this hyponatremia is often diagnosed as syndrome of inappropriate diuretic hormone (SIADH). Fluid restriction is usually the first line of treatment. However, this can exacerbate vasospasm and produce resultant ischemia. Cerebral salt wasting is a syndrome of renal sodium loss that may occur commonly after central nervous system injury, yet remains unrecognized. Treatment of cerebral salt wasting consists of hydration and salt replacement. This article uses a case report to discuss the importance of recognition of this syndrome, and treatment concerns are reviewed.
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PMID:Cerebral salt wasting syndrome in brain injury patients: a potential cause of hyponatremia. 916 78

A method to reduce ischemia-reperfusion (I/R) injury can be an important criterion to improve the preservation solution. Although University of Wisconsin solution (UW) works as a lung preservation solution, its attenuation effect on I/R injury has not been investigated. We attempted to determine whether, by adding various protective agents, modified UW solutions will enhance the I/R attenuation by UW. We examined the I/R injury in an isolated rat lung model. Various solutions, e.g., physiological salt solution (PSS), UW, and modified UW solutions containing various protective agents such as prostaglandin E1, dexamethasone, U-74389G, or dibutyryl adenosine 3',5'-cyclic monophosphate were perfused individually to evaluate the I/R injury. Isolated rat lung experiments, with ischemia for 45 min, then reperfusion for 60 min, were conducted in a closed circulating system. Hemodynamic changes, lung weight gain (LWG), capillary filtration coefficient (Kfc), protein content of lavage fluid, concentration of cytokines, and lung histopathology were analyzed. Results showed that the acute I/R lung injury with immediate permeability pulmonary edema was associated with an increase in tumor necrosis factor-alpha (TNF-alpha) production. A significant correlation existed between TNF-alpha and Kfc (r = 0.8, P < 0.0001) and TNF-alpha and LWG (r = 0. 9, P < 0.0001), indicating that TNF-alpha is an important cytokine modulating early I/R injury. Significantly lower levels of Kfc, LWG, TNF-alpha, and protein concentration of lung lavage (P < 0.05) were found in the UW-perfused group than in the control group perfused with PSS. Modified UW promoted the protective effect of UW to further decrease Kfc, LWG, and TNF-alpha (P < 0.05). Histopathological observations also substantiated this evidence. In the UW+U-74389G group, bronchial alveolar lavage fluid contained lowest protein concentration. We conclude that the UW solution attenuates I/R injury of rat lung and that the modified UW solutions further enhance the effect of UW in reducing I/R injury. Among modified solutions, UW+U-74389G is the best. Further investigation of the improved effects of the modified UW solutions would be beneficial in lung transplantation.
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PMID:PGE1, dexamethasone, U-74389G, or Bt2-cAMP as an additive to promote protection by UW solution in I/R injury. 926 56

To assess the efficacy of losartan (2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphe nyl-4-yl)methyl]imidazole, potassium salt), an angiotensin II receptor antagonist, on acute myocardial ischemia, 36 four-month-old spontaneously hypertensive rats were used. The animals underwent 45 min of left coronary artery occlusion and 1 h of reperfusion and were randomly assigned to control and losartan-treated groups (2, 5, and 10 mg/kg, intravenously). Losartan was administered 15 min before ischemia. Electrocardiograms (lead II) were monitored continuously throughout the experiment. To assess the anti-infarct effect of losartan, the area at risk was determined by methylene blue dye and the infarct size was determined by nitroblue tetrazolium chloride staining. The areas of risk and infarct were measured by computerized planimetry. Results demonstrated that the low and intermediate doses (2 and 5 mg/kg) of losartan significantly decreased the incidence of ventricular fibrillation and mortality during the ischemic period induced by left coronary artery occlusion. However, a significant reduction in infarct size, calculated as a percentage of the area at risk, was noted in all three losartan-treated groups (control: 41.5% +/- 5.2%, losartan, 2 mg/kg: 11.2% +/- 5.8%, 5 mg/kg: 8.5% +/- 2.7% and 10 mg/kg: 13.7% +/- 1.6%). The results suggest that losartan may be useful in the treatment of ventricular arrhythmias induced by acute myocardial infarction and attenuation of reperfusion injury in hypertension.
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PMID:Losartan attenuates myocardial ischemia-induced ventricular arrythmias and reperfusion injury in spontaneously hypertensive rats. 927 79

L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl- 2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl hydrogen phosphate] potassium salt (EPC-K1), a phosphate diester of alpha-tocopherol and ascorbic acid, is a potent antioxidant. We examined the effects of EPC-K1 on ischemia-reperfusion injury in the skeletal muscle of rats, using an ischemic revascularized hind limb model. Warm ischemia (25 degrees C), produced by vascular pedicle clamping, was sustained for 4 hours. After 24 hours of reperfusion, skeletal muscle injury was evaluated in 2 groups: one group treated by intravenous injection of EPC-K1 (10 mg/kg) prior to ischemia, and a group of controls. The EPC-K1-treated group showed a statistically significant amelioration in the reduction of the isometric muscle contraction, inhibition of the elevation of the muscle wet- to dry-weight ratio, limitation of the muscle level of thiobarbituric acid reactive substances and the serum levels of creatine phosphokinase, lactate dehydrogenase and mitochondrial glutamic oxaloacetic transaminase, and reduction of the extent of muscle injury according to the histological findings. These observations indicate that EPC-K1 acted effectively on ischemia-reperfusion injury in the rat skeletal muscle and thereby improved muscle function.
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PMID:Reduced ischemia-reperfusion injury in muscle. Experiments in rats with EPC-K1, a new radical scavenger. 931 42

We present a new hypothesis to explain the development of salt-dependent hypertension in humans. We propose that hypertension has two phases: an early phase in which elevations in blood pressure (BP) are mainly episodic and are mediated by a hyperactive sympathetic nervous or renin-angiotensin system, and a second phase in which BP is persistently elevated and that is primarily mediated by an impaired ability of the kidney to excrete salt (NaCl). We propose that the transition from the first phase to the second occurs as a consequence of catecholamine-induced elevations in BP that preferentially damage regions of the kidney (juxtamedullary and medullary regions) that do not autoregulate well to changes in renal perfusion pressure. The catecholamine response is associated with both an increase in peritubular capillary pressure and a reduction in peritubular capillary plasma flow, resulting in injury to the peritubular capillaries with ischemia to the tubules and interstitium. The local injury triggers the release or activation (angiotensin II, adenosine, renal sympathetic nerves) or inhibition (nitric oxide, prostaglandins, dopamine) of vasoactive mediators that further augment ischemia and result in abnormal tubuloglomerular feedback and enhanced NaCl reabsorption. The peritubular capillary injury with rarefaction simultaneously blunts the pressure natriuresis mechanism. The combined effect of enhanced tubuloglomerular feedback and impaired pressure natriuresis results in a defect in NaCl excretion which, on the exposure to salt, results in the development of persistent hypertension. Evidence is provided to suggest that this may be the major mechanism for the development of salt-dependent hypertension, and particularly for the hypertension associated with blacks, aging and obesity. Thus, essential hypertension may be a type of acquired tubulointerstitial renal disease.
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PMID:Hypothesis: the role of acquired tubulointerstitial disease in the pathogenesis of salt-dependent hypertension. 935 Jun 40

The release of endogenous acetylcholine was measured in electrically (5-20 Hz) stimulated guinea pig cerebral cortex and caudate nucleus slices under ischemic (hypoxic and glucose-free) conditions. Ischemia reduced acetylcholine release by 40-90%; the inhibition depended on the duration of ischemia (10-30 min) while the extent of post-ischemic recovery was inversely related to it. Caudate nucleus slices displayed a higher sensitivity to ischemia than did cortical slices. To test the effects of excitatory amino acid receptor antagonists on the ischemia-induced reduction of acetylcoline release and on its post-ischemic recovery, the following drugs were used: 5-methyl-10,11-dihydro-5-H-dibenzo-[a,b]-cyclohepten-5,10-imine (MK-801,-a blocker of the N-methyl-D-aspartate [NMDA] receptor-linked channel), 7-chloro-kynurenic acid (7-Cl-KYN) and (E)-3-[2(phenylcarbamoyl)ethenyl]-4,6-dichloroindole-2-carboxylic acid sodium salt (GV150526A, blockers of the glycine site of the NMDA receptor), eliprodil, (an antagonist at the polyamine site of the NMDA receptor), and 6-cyano- 7-nitro-quinoxalin-2,3-dione (CNQX, a D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionic acid [AMPA] receptor antagonist). These did not modify the time-course and the extent of ischemia-induced inhibition but improved post-ischemic recovery in a concentration dependent manner. GV 150526A and CNQX appeared to be more effective in the cerebral cortex. Only eliprodil was devoid of any effect in both areas. The evaluation of acetylcholine release from brain slices represents a suitable in vitro model to quantify the effectiveness of drugs in favouring recovery from the cholinergic presynaptic failure induced by ischemic conditions. The different effects of the excitatory amino acid receptor antagonists cited above, depending on the brain areas considered and the receptor subtypes involved, may be of interest in view of their therapeutic potential.
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PMID:Post-ischemic recovery of acetylcholine release in vitro: influence of different excitatory amino acid receptor subtype antagonists. 941 43


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