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 effects of dichloroacetate (DCA) on brain lactate, intracellular pH (pHi), phosphocreatine (PCr), and ATP during 60 min of complete cerebral ischemia and 2 h of reperfusion were investigated in rats by in vivo 1H and 31P magnetic resonance spectroscopy; brain lactate, water content, cations, and amino acids were measured in vitro after reperfusion. DCA, 100 mg/kg, or saline was infused before or immediately after the ischemic period. Preischemic treatment with DCA did not affect brain lactate or pHi during ischemia, but reduced lactate and increased pHi after 30 min of reperfusion (p < 0.05 vs. controls) and facilitated the recovery of PCr and ATP during reperfusion. Postischemic DCA treatment also reduced brain lactate and increased pHi during reperfusion compared with controls (p < 0.05), but had little effect on PCr, ATP, or Pi during reperfusion. After 30 min of reperfusion, serum lactate was 67% lower in the postischemic DCA group than in controls (p < 0.05). The brain lactate level in vitro was 46% lower in the postischemic DCA group than in controls (p < 0.05). DCA did not affect water content or cation concentrations in either group, but it increased brain glutamate by 40% in the preischemic treatment group (p < 0.05). The potential therapeutic effects of DCA on brain injury after complete ischemia may be mediated by reduced excitotoxin release related to decreased lactic acidosis during reperfusion.
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PMID:Effect of dichloroacetate on recovery of brain lactate, phosphorus energy metabolites, and glutamate during reperfusion after complete cerebral ischemia in rats. 135 94

This study tested the hypothesis that preventing neutrophil adhesion during reperfusion, by blocking either the neutrophil membrane CD18 integrin complex or its endothelial and myocyte ligand, intercellular adhesion molecule-1 (ICAM-1), would reduce myocardial inflammation and edema and improve reflow and ventricular function after heart preservation and transplantation. After cardioplegia and insertion of a left ventricular balloon, rabbit hearts were heterotopically transplanted into recipient rabbits either immediately (immediate, n = 12) or after preservation in 4 degrees C saline (3 hours of ischemia, n = 33). Forty-five minutes before reperfusion, recipients of preserved hearts received intravenous infusions of either saline (vehicle, n = 13), anti-CD18 monoclonal antibody (Mab) R15.7 (2 mg/kg) (anti-CD18, n = 10), or anti-ICAM-1 Mab R1.1 (2 mg/kg) (anti-ICAM, n = 10). During 3 hours of reperfusion the slope of the peak-systolic pressure-volume relation and its volume-axis intercept, the exponential elastic coefficient of the end-diastolic pressure-volume relation, the unstressed ventricular volume, and the time constant of the exponential left ventricular pressure decay after dP/dtmin were serially measured. Myocardial blood flow was measured with microspheres from which coronary vascular resistance was calculated. After explanation, the degree of myocardial inflammation, estimated by tissue neutrophil sequestration (myeloperoxidase assay) and myocardial water content were determined. Within each group no significant differences in measurements made at 1, 2, and 3 hours of reperfusion were noted. Compared with the immediate transplantation group, the vehicle group demonstrated a significant increase in myeloperoxidase activity (3380 +/- 456 versus 1712 +/- 552 microU/gm, p < 0.05), coronary vascular resistance (115.5 +/- 13.4 versus 70.5 +/- 10.6 U/gm, p < 0.05), and myocardial water content (79.8% +/- 0.4% versus 75.6% +/- 1.3%, p < 0.05), a significant decrease in unstressed ventricular volume (a leftward shift in the end-diastolic pressure-volume relation) (-0.49 +/- 0.24 versus 0.28 +/- 0.21 ml, p < 0.05), and a marked prolongation in exponential left ventricular pressure delay after dP/dtmin (156.64 +/- 3.81 versus 37.25 +/- 3.34 msec, p < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Complete prevention of myocardial stunning, contracture, low-reflow, and edema after heart transplantation by blocking neutrophil adhesion molecules during reperfusion. 136 May 56

Eight stroke patients were examined serially in the acute phase and 1 week and 2-4 weeks after stroke with water-suppressed proton magnetic resonance spectroscopy. The time courses of lactate level and regional cerebral blood flow were studied. A high lactate level was found in the acute phase. The lactate content decreased to barely detectable levels during the following 3 weeks, while regional blood flow increased during this period. The inverse relationship between lactate level and cerebral blood flow suggests that lactate plays no substantial role in the vasodilatation underlying the hyperemia that follows reperfusion. The amount of lactate present in the acute phase reflects the severity of ischemia in the affected region. The lactate level was still above normal in the subacute phase with hyperemia, suggesting lactate production through aerobic glycolysis. Thus, the lactate level in the subacute phase probably does not reflect the degree of anaerobic glycolysis in hypoxic neuronal tissue.
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PMID:Cerebral lactate production and blood flow in acute stroke. 834 65

I.p. injection (5 g crude drug/kg) of water extract of Salvia miltiorrhiza to S.D. rats can prevent the acute cardial ischemia induced by the ligation of the coronary artery. The elevation of S-T segment in the electrocardiogram caused by the ischemia was greatly reduced in animals treated with Salvia miltiorrhiza compared with control group. The ischemia area in the left ventricle was significantly reduced and survival rate of the rats increased.
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PMID:[Effect of Salvia miltiorrhiza on the cardial ischemia in rats induced by ligation]. 139 96

Mechanical ventilation with high levels of positive end-expiratory pressure (PEEP) decreases hepatic blood flow (HBF) and hepatic oxygen delivery (HO2D). Noninvasive methods of detecting decreased HBF might prevent hepatic ischemia and dysfunction. Monoethylglycinexylidide (MEGX) is a hepatic metabolite of lidocaine, used clinically to determine graft function following hepatic transplantation. In order to test the hypothesis that MEGX production would be affected by changes in hepatic hemodynamics associated with lung injury, 12 dogs were instrumented with femoral and pulmonary artery catheters. Splenectomy was performed and the portal and hepatic veins cannulated. The hepatic artery and portal vein were encircled with flow probes. Lung injury was induced in six animals (INJURED group) with oleic acid (0.08 mL/kg) and 10 cm H2O PEEP was added to correct subsequent shunt. Levels of MEGX were measured 15 minutes after injection of intravenous lidocaine (1 mg/kg). Levels of HBF, HO2D, and MEGX were measured at BASELINE, after lung injury (INJURY time point), and after addition of PEEP (PEEP time point). CONTROL animals (n = 6) were studied at the same time points but without lung injury or PEEP. Hepatic blood flow and hepatic oxygen delivery were significantly decreased after lung injury and further decreased after PEEP. Levels of MEGX were unchanged in the CONTROL group but were significantly reduced by lung injury and PEEP in the INJURED group. Decreased MEGX production may be a useful clinical indicator of reduced hepatic flow and oxygen supply in critical illness.
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PMID:Monoethylglycinexylidide production parallels changes in hepatic blood flow and oxygen delivery in lung injury managed with positive end-expiratory pressure. 140 22

Mechanical ventilation with positive end-expiratory pressure (PEEP) limits hepatic blood flow (HBF) and oxygen delivery (HO2D). Early gut feeding may augment hepatic hemodynamics and avoid relative ischemia in this flow-limited environment. To examine these effects, canines were instrumented with arterial, pulmonary artery, portal, and hepatic vein catheters. Splenectomy and gastrostomy were performed and the hepatic artery and portal vein were encircled with flow probes. All animals underwent lung injury with oleic acid (0.08 ml/kg) followed by the addition of 10 cm H2O PEEP to correct shunt. One group (fed) was then given a bolus elemental feeding (1 kcal/ml, 10 ml/kg) and the Control group, sterile water. Cardiac index (CI), HBF, hepatic oxygen delivery (HO2D), and hepatic oxygen consumption (HO2C) were measured at baseline (T0), after PEEP (T1), and 1 (T2) and 2 hr (T3) after feeding. Data were tested for significant changes between time points in the same group by ANOVA and significant differences were subjected to t testing. PEEP significantly decreased CI, HBF, and HO2D compared to baseline. Subsequently, gut feeding increased HBF to baseline levels and improved HO2D. HO2C also increased but hepatic O2 extraction was unchanged. There was little change noted in the control group over this same period. We conclude that gut feeding augments HBF and HO2D in this flow-limited state and may preserve splanchnic integrity in critical illness.
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PMID:Gut feeding and hepatic hemodynamics during PEEP ventilation for acute lung injury. 140 14

Oxygen-derived free radicals are now considered important contributors to tissue injury associated with ischemia and reperfusion. The purpose of this study was to determine the influence of oxygen free radical scavengers on reperfusion injury. The left lower lobes of 15 canine lungs were isolated, preserved, and then reperfused for 120 minutes. Three groups of lobes were studied: Group 1 (n = 5), without ischemia, group 2 (n = 5) four hours of cold ischemia in Euro-Collins solution, group 3 (n = 5) four hours cold ischemia+oxygen free radical scavenger glutathione (0.1 nmol/L) given at the moment of perfusion. Extravascular lung water (grams per gram of blood-free dry lobe weight) after reperfusion was 2.82 +/- 0.32, 5.06 +/- 0.45, 4.21 +/- 0.33 for groups 1 through 3 respectively (p less than 0.001 group 1 versus group 2, p less than 0.001 group 2 versus group 3). Lung tissue lipid peroxidation, measured as thiobarbituric acid reactive material was 125 +/- 11, 270 +/- 30, and 185 +/- 17 nmol/g dry lobe weight for groups 1, 2 and 3 respectively (p less than 0.05 group 2 versus 1 and group 3 versus group 2). The data suggest that oxygen free radical scavengers attenuate reperfusion injury.
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PMID:Oxygen free radical scavengers and reperfusion injury in dog lung preserved in cold ischemia. 141 81

The purpose of the present investigation was to establish whether pretreatment with selenium enhances the stores of selenium-dependent glutathione peroxidase in the tissues and to verify if and to what extent alterations of mechanical and biochemical cardiac properties induced by ischemia in the myocardium may be thus prevented. Ten rats had sodium selenite (6 micrograms/day) added to their drinking water for 4 weeks, while 10 control rats received no treatment. At the end of 4 weeks, the hearts were perfused by the Langendorff technique with oxygenated Krebs-Henseleit solution at a rate of 10 ml/min for 30 minutes at 37 degrees C. Ischemia was then induced by reducing the perfusion to 1 ml/min for 60 minutes; reperfusion followed at the control rate for a further 30 minutes. Isometrically developed pressure and its maximum first derivative at different ventricular volumes was measured before and after the ischemic period. Lactate and creatine kinase activity were measured in the effluent throughout. Tissue concentrations of adenine nucleotides and creatine phosphate and lutathione peroxidase activity were estimated after reperfusion. The rats treated with selenium showed a wide-spread increase in the activity of Se-dependent glutathione peroxidase in all tissues. There was an improved recovery of ventricular contraction during reperfusion and an increased myocardial content of adenine nucleotides and creatine phosphate. During reperfusion, the loss of creatine kinase into the perfusate was less in the treated animals, and there was a similar trend for the production of lactate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effect of selenium in cardiac ischemia and reperfusion. 142 Sep 51

Because the three distinct fiber types of skeletal muscle have significant metabolic differences, the predominant fiber type in a muscle may influence its sensitivity to injury from ischemia and reperfusion. The few studies to address this issue have been conflicting. We explored possible differences in the sensitivity of fiber types to ischemia/reperfusion injury with an isolated rat hindlimb preparation perfused with an albumin-enriched Krebs buffer. Following 120 min of ischemia and 60 min of reperfusion, the tibialis anteriorwhite, tibialis anteriorred, soleus, and plantaris muscles were assessed for injury by examining three parameters: skeletal muscle injury (via 99Tc-pyrophosphate), microvascular injury (via 125I-albumin), and tissue water content. There was no consistent correlation between fiber type and sensitivity to postischemic injury. Both the soleus (slow twitch) and plantaris (fast twitch) muscles sustained similar significant injury: muscle damage was 133 and 167% greater than controls, and microvascular damage 96 and 91% greater than controls, respectively. However, other fast twitch muscles (tibialis anteriorwhite and tibialis anteriorred) exhibited no significant injury. Both injured muscles were in the posterior compartment while the uninjured muscles were in the anterior compartment. Regional flow as measured by microspheres revealed no correlation between postischemic flow and muscle injury, microvascular injury, or compartmental location. Skeletal muscle fiber type was not consistently predictive of its sensitivity to ischemia/reperfusion-induced injury. Compartmental location may have played an as yet unknown role in modulating vulnerability to postischemic damage.
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PMID:Skeletal muscle fiber type does not predict sensitivity to postischemic damage. 143 5

Lazaroids are a class of novel 21 aminosteroids. They have been reported to be potent inhibitors of lipid peroxidation, which is a major contributing factor to ischemia-reperfusion injury in the lung. A Lewis rat orthotopic left lung isotransplant model was used to investigate the effects of the lazaroid U74500A on pulmonary preservation. The heart-lung blocks of donor rats were flushed with and then stored in either standard University of Wisconsin solution or University of Wisconsin solution with 30 mumol/L of U74500A substituted for the dexamethasone. After 6 or 12 hours of cold storage at 0 degrees C, the left lungs were transplanted into recipient rats and reperfused for 1 hour. Pulmonary function was assessed by measuring oxygen and carbon dioxide tensions in arterial blood after removal of the right lung. Lipid peroxide concentrations were measured as a thiobarbituric acid-reactive substance. Although arterial oxygen and carbon dioxide pressures and water content after 6 hours of preservation followed by reperfusion were similar in both the lazaroid and dexamethasone groups, lipid peroxide concentration was significantly higher in the dexamethasone group (0.88 +/- 0.07 mumol/gm) than in the lazaroid group (0.54 +/- 0.07 mumol/gm) (p < 0.01). After 12 hours of preservation, there were significant differences between the lazaroid and dexamethasone groups in arterial oxygen pressure (339 +/- 70 vs 27 +/- 3 mm Hg, p < 0.01), arterial carbon dioxide pressure (24.3 +/- 2.7 vs 47.7 +/- 7.0 mm Hg, p < 0.001), and lipid peroxide concentrations (0.69 +/- 0.07 vs 1.30 +/- 0.09 mumol/gm, p < 0.001). We conclude that addition of U74500A to the flush and storage solution enhances the preservation of the pulmonary graft in this transplant model.
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PMID:Lazaroid U74500A as an additive to University of Wisconsin solution for pulmonary grafts in the rat transplant model. 143 15


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