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

We evaluated a spectrophotometric nitroblue tetrazolium (NBT) reduction assay as a technique to quantitate experimental intestinal ischemic injury. NBT is a tetrazolium salt that is reduced by mitochondrial coenzymes to form a blue formazan dye which can be measured on a spectrophotometer. We used a rat model of progressive intestinal ischemia to compare NBT reduction with standard histologic grading by light microscopy. Isolated segments of small intestine were made ischemic for periods of 15, 30, 60, 90, and 120 min in each of five rats (no reperfusion). A portion of each segment was prepared for both NBT reduction assay and blinded histologic grading. The reproducibility of these results was then tested in a second identical study of four rats (Part 2). When compared to nonischemic segments of intestine, NBT reduction was significantly decreased after 30 min of ischemia (P < 0.05, ANOVA) and continued to decrease as ischemic time increased. These findings were reproduced in the second experimental group. Overall, NBT reduction correlated closely with duration of ischemia (r = 0.81, P < 0.001) and histologic grade (r = 0.77, P < 0.001). Based on criteria developed in Part 1, NBT reduction had a sensitivity of 100% and a specificity of 94% for detecting ischemia > or = 30 min in Part 2. We conclude that the spectrophotometric NBT assay in an accurate technique for quantitating small intestinal ischemic injury which also gives useful information about the functional status of mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quantitating intestinal ischemia with nitroblue tetrazolium salts. 772 12

Effect of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1- benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1, CAS 127061-56-7), a diester of alpha-tocopherol and ascorbic acid, on transient cerebral ischemia was studied in Mongolian gerbils. Cerebral energy metabolism and intracellular pH (pHi) were estimated employing in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Intraperitoneal injection of EPC-K1 (5 or 10 mg/kg) prior to ischemia significantly ameliorated pHi reduction in a dose dependent manner during ischemia. After reperfusion, energy and pHi recoveries were significantly faster in the EPC-K1 groups than in the control group. EPC-K1 (10 mg/kg) significantly reduced the extent of cerebral edema. Moreover, administration of EPC-K1 immediately after reperfusion significantly shortened the consciousness recovery in a dose dependent manner. The results suggest that EPC-K1 may exert protective effects on ischemic brain and may have therapeutic value in ischemic stroke.
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PMID:Effects of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1- benzopyran-6yl-hydrogen phosphate] potassium salt on cerebral energy state and consciousness recovery following transient forebrain ischemia in gerbils. 798 54

The activity of 1-alkyl-sn-glycero-3-phosphate (AGP) acetyltransferase was studied using microsomal fractions isolated from cerebral cortices of 15-day-old rabbits. Fraction P3A was isolated using buffered 0.32 M sucrose containing mercaptoethanol, EDTA and NaF. This fraction had specific AGP acetyltransferase activities which were 4.9-times those of microsomal fraction P3B isolated in 0.32 M sucrose alone. This P3B activity was increased 2.4-times after a preincubation in the presence of ATP, MgCl2 and a high-speed supernatant fraction from cerebral cortex. Further, the activities of both P3A and P3B were almost completely eliminated by preincubation in the presence of alkaline phosphatase. Thus an activation of the AGP acetyltransferase by phosphorylation was indicated. While there was little inhibition of the P3A AGP acetyltransferase in the presence of added ATP, the magnesium salt form of ATP (1 mM) was severely inhibitory, bringing about 86% inhibition for P3A and 91% for P3B. The inhibitory effects of MgADP and MgAMP were smaller, and MgATP was a much more effective inhibitor than MgCTP, MgGTP and MgUTP which brought about 20-38% inhibitions of P3A activity at 1 mM concentrations. The effect of MgATP may be of particular relevance to the synthesis of platelet activating factor (PAF) following a period of ischemia in brain. Falling MgATP levels during energy failure could relieve the inhibition of AGP acetyltransferase seen in healthy cells and allow the formation of 1-alkyl-2-acetyl-sn-glycero-3-phosphate, which is the first committed intermediate in the de novo pathway of PAF synthesis.
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PMID:MgATP inhibits the synthesis of 1-alkyl-2-acetyl-sn-glycero-3-phosphate by microsomal acetyltransferase of immature rabbit cerebral cortex. 801 76

Recent studies have suggested that modifications in mitochondrial F1-adenosinetriphosphatase (ATPase) activity may play an important role in the regulation of myocardial oxidative phosphorylation. The goal of the present study was to develop and characterize an assay of F1-ATPase activity that could be performed repeatedly on an intact heart under various physiological states. With the use of submitochondrial particles prepared from biopsy samples of canine myocardium, we found reproducible F1-ATPase activity when normalized to the activity of the intramitochondrial enzyme citrate synthase. The oligomycin-sensitive component of the ATPase activity was found to be mainly F1-ATPase. F1-ATPase activity of normal myocardium increased by incubation in high salt-pH buffer, suggesting baseline inhibition. Five minutes after global ischemia, F1-ATPase activity decreased to 60% of baseline. Hypoxia for 10 min resulted in no significant change in F1-ATPase activity. With phenylephrine infusion, myocardial oxygen consumption more than doubled, whereas F1-ATPase activity increased by approximately 30%. Both returned to baseline levels after discontinuation of the drug. With the use of an assay developed to measure F1-ATPase activity of intact myocardium, changes of the enzyme activity were found during both ischemia and at increased work loads. These data suggest that alterations of F1-ATPase activity may contribute to the regulation of myocardial oxidative phosphorylation.
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PMID:Mitochondrial F1-ATPase activity of canine myocardium: effects of hypoxia and stimulation. 802 1

A fatal case of poisoning due to ingestion of an apparently innocuous household product is described. A healthy 28-year-old man accidentally drank floor polish (Cristalizador, a Spanish import). On arrival at the emergency room a few hours later he passed large amounts of bloody stool and lost consciousness. A call to the Spanish Poison Center revealed that although not indicated on the label, the polish contained a highly poisonous salt, fluoro-silicate. Blood gas analysis revealed severe metabolic acidosis. Serum calcium was 3.8 mg/dL. The post-resuscitation ECG showed subendocardial ischemia and ST-elevation in the anteroseptal wall and prolonged QT-interval. In the intensive care unit he received large amounts of fluids, dopamine, sodium bicarbonate and calcium. Despite the treatment, his condition continued to deteriorate: VPB's appeared, there was a short run of ventricular tachycardia and then atrial fibrillation developed. Further treatment included lidocaine, verapamil, amiodarone, and electrical cardioversion. Blood pressure remained low and 11 hours after admission he died of myocardial infarction, severe arrhythmia and multi-organ failure.
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PMID:[Death from fluoro-silicate in floor polish]. 818 3

Chronic nitric oxide (NO) inhibition promotes hypertension and ischemic glomerular injury with only minor glomerulosclerosis (GS). We evaluated the effect of superimposed salt overload, which has been shown to aggravate GS in other models. Fifteen days of treatment with the NO inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) promoted marked arterial and glomerular hypertension, hyporeninemia, and slight renal interstitial expansion, but no glomerular injury. Salt overload slightly exacerbated systemic and glomerular hypertension, promoted albuminuria, interstitial expansion, and glomerular ischemia, and paradoxically reversed hyporeninemia. The angiotensin II inhibitor losartan attenuated glomerular and systemic hypertension and prevented renal injury in these rats. Thirty days of treatment with L-NAME resulted in marked hypertension, hyperreninemia, interstitial expansion, and glomerular ischemia. Concomitant salt overload exacerbated hypertension, interstitial expansion, and ischemia and promoted massive albuminuria, GS, and creatinine retention. Losartan attenuated these effects. Sodium overload aggravates the renal and systemic consequences of chronic NO inhibition by mechanisms that may include paradoxical activation of renin secretion. Interstitial expansion and glomerular ischemia, rather than GS, constitute the chief modalities of renal injury in this model.
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PMID:Sodium excess aggravates hypertension and renal parenchymal injury in rats with chronic NO inhibition. 820 52

This study was undertaken to determine the effect of dichloroacetate (DCA) on myocardial functional and metabolic recovery following global ischemia. Sixteen isolated rabbit hearts were subjected to 120 minutes of mildly hypothermic (34 degrees C) cardioplegic arrest with multi-dose, modified St. Thomas' cardioplegia. Following ischemia, hearts were reperfused with either a physiologic salt solution (PSS) as controls, (CON, N = 10), or PSS containing DCA (DCA, N = 6) at a concentration of 1 mmol/L. Functional and metabolic indices were determined at baseline and at 15, 30, and 45 minutes of reperfusion. Results were analyzed using analysis of variance (ANOVA, Sheffe F test) and significance was defined as P < 0.05. Functional recovery was significantly better in hearts reperfused with DCA. Developed pressure (DP) recovered to 62 +/- 4% of baseline in DCA hearts, compared to 37 +/- 8% in CON hearts. Recovery of dP/dt was also improved in DCA versus CON hearts (67 +/- 5 v 43 +/- 10%). Coronary blood flow was not different between groups either at baseline or during reperfusion, but myocardial oxygen consumption (MVO2) was increased in the DCA versus CON hearts (71 +/- 10% of baseline, v 51 +/- 19%). Diastolic compliance during reperfusion was improved in those hearts receiving DCA, as was myocardial mechanical use efficiency (DP/MVO2). Correction of myocardial tissue pH to baseline values was similar in both groups, indicating that the beneficial effect on functional recovery seen with DCA was not solely related to amelioration of acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dichloroacetate enhances myocardial functional and metabolic recovery following global ischemia. 820 12

In the ventilated ischemic lung, oxygen tension will increase at a time when glucose depletion may impair antioxidant defenses, thereby predisposing the lung to injury mediated by oxygen radicals. In the unventilated ischemic lung, however, glucose depletion in the setting of low oxygen tension may decrease production of ATP, leading to injury by a different mechanism. In this study, we evaluated the role of both oxygen tension and glucose concentration on ischemic injury in isolated ferret lungs. Injury, defined as an increase in vascular permeability, was assessed by measurement of filtration coefficient (Kf) and osmotic reflection coefficient for albumin (sigma alb) after 3 h of normothermic (37 degrees C) ischemia without reperfusion. Lungs were ventilated with either 95% O2-5% CO2 or 0% O2-5% CO2. The vasculature was flushed with physiological salt solution containing either 15 mM glucose (hyperoxia-glucose, anoxia-glucose), 15 mM sucrose (hyperoxia-sucrose, anoxia-sucrose), or no substrate (hyperoxia-no substrate, anoxia-no substrate) (n = 6 for each condition). Kf and sigma alb in hyperoxia-no substrate group did not differ from values in minimally ischemic normoxic normoglycemic ferret lungs. Without glucose, ischemic injury was worse in anoxic than in hyperoxic lungs. With glucose, ischemic injury was worse in hyperoxic than in anoxic lungs. Glucose exacerbated injury in hyperoxic, but not anoxic, lungs. These results indicate that ischemic injury in these lungs depended on both oxygen tension and glucose concentration and suggest that both oxygen radical generation and ATP depletion during ischemia may contribute to the development of this injury.
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PMID:Effects of oxygen tension and glucose concentration on ischemic injury in ventilated ferret lungs. 822 35

Inhibitors of Na+/H+ exchanger are reported to exert an anti-ischemic effect. Some calcium antagonists and particularly bepridil are commonly used as anti-ischemic agents. Therefore, in this study, we test the hypothesis that protective effect against ischemia may occur at least in part through an action on Na+/H+ exchanger. The effect of some calcium antagonists on Na+/H+ exchanger from acid-loaded and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt (DIDS)-treated human red cells (RBC) has been studied with a pHstat technique. Doses above those required to affect calcium channel (10(-5) and 10(-4) M) of nifedipine, nicardipine, verapamil and diltiazem had no effect on Na+/H+ exchanger activity. Ethyl isoproply amiloride (10(-4) M) completely inhibited the exchanger. Among the calcium antagonists tested, bepridil exhibited a particular effect, dissipating the pH gradient independently from the Na+/H+ exchanger activity. Bepridil's effect on DIDS-treated RBC was compared with that of a well known protonophore, carbamyl cyanide p-(trifluoromethoxy)phenyl hydrazone, and with that of tributyltin, which mediates a Cl-/OH- exchange across the cell membrane. Bepridil (> 2 x 10(-6) M) acts like tributyltin by dissipating the pH gradient whatever the external cation (Na+ or K+) or the membrane potential, and its action depends on the ratio intracellular [Cl-]/extracellular [Cl-]. The dissipation seems to occur through an OH-/Cl- exchange but other mechanisms may intervene. Moreover, intraerythrocytic pH measurement by 31P nuclear magnetic resonance clearly showed that bepridil permits the cell to recover normal pH faster than control.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chloride dependent intracellular pH increase induced by bepridil in human red blood cells: a possible involvement in correction of ischemic acidosis. 826 12

Reperfusion after global cardiac ischemia may injure coronary artery endothelium and lead to vasospasm and thrombosis. Oxygen-derived radicals have been implicated as mediators of this process, but the precise mechanism of injury is unknown. We hypothesized that oxygen-derived radicals impair coronary endothelial production of nitric oxide, a potent endogenous vasodilator and inhibitor of platelet adhesion. To test this theory, we developed an in vitro model of reperfusion injury in which segments of epicardial canine coronary artery were suspended in organ chambers (physiologic salt solution, 37 degrees C, 95% oxygen and 5% carbon dioxide) and exposed to oxygen-derived radicals (generated by adding xanthine [10(-4) mol/L] and xanthine oxidase [100 mU/ml] to the bathing solution for 70 minutes). After exposure to oxygen-derived radicals, epicardial coronary artery smooth muscle exhibited normal contraction to potassium ions (20 mmol/L) and prostaglandin F2 (4 x 10(-6) mol/L); also, the rings relaxed normally on exposure to isoproterenol and sodium nitroprusside (10(-9) to 10(-4) mol/L) (n = 6). In contrast, endothelium-dependent vasodilatation to receptor-dependent agonists acetylcholine and adenosine diphosphate (10(-9) to 10(-4) mol/L) was impaired as compared with the reaction of control vessels not exposed to oxygen-derived radicals (n = 18, P < 0.001, and n = 10, P < 0.002, respectively). Importantly, receptor-independent, endothelium-dependent relaxation to the calcium ionophore A23187 was normal (n = 6). Further, endothelium-dependent vasodilatation to receptor-dependent agonist bradykinin (non-nitric oxide pathway) was normal after exposure to oxygen-derived radicals. This is the first study to demonstrate that oxygen-derived radicals selectively impair receptor-dependent nitric oxide production by the coronary endothelium. Diminished nitric oxide production is a likely mechanism of vasospasm and thrombosis after reperfusion of the ischemic heart.
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PMID:Oxygen radical-mediated vascular injury selectively inhibits receptor-dependent release of nitric oxide from canine coronary arteries. 830 70


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