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

The free fatty acid (FFA) and triacylglycerol content and composition are compared in the mouse and toad brain during ischemia. Mouse brain FFA are rapidly increased after decapitation, the maximal production rates being attained within the first minutes. Free arachidonic and stearic acids undergo the highest increases, followed by palmitic, oleic and docosahexaenoic. In contrast, toad brain FFA only changes significantly several hours after decapitation. Triacylglycerols remain virtually unmodified in the amphibian brain during ischemia, whereas in the mammal they are partially decreased, reaching a nearly steady level at about 10 min. This triglyceride breakdown may represent a part, but cannot account for all the changes taking place in FFA. Uneven contributions to the FFA are shown for their counterparts in triacylglycerols. Although the neutral glycerides could be the source of free palmitic acid, they are not responsible for the increases in arachidonic and stearic acids. It is suggested that FFA mainly arise from polar lipid deacylation and a relationship is suggested between the slowness of FFA changes and the higher resistance of poikilotherms to oxygen deprivation.
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PMID:Differential lipid deacylation during brain ischemia in a homeotherm and a poikilotherm. Content and composition of free fatty acids and triacylglycerols. 81 Feb 21

Intracerebral administration of [3H]arachidonic acid ([3H]ArA) into 19-20-day-old rat embryos, resulted in a rapid incorporation of label into brain lipids. One hour after injection, 55.6 +/- 8.2, 18.0 +/- 3.4, and 13.7 +/- 1.3% of the total radioactivity was associated with phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine, respectively. Approximately 10% of radioactivity was found acylated in neutral lipids of which free ArA comprised only 1.5 +/- 0.2% of the total radioactivity. Complete restriction of the maternal-fetal circulation for < or = 40 min did not affect the rate of [3H]ArA incorporation (t1/2 = 2 min) into fetal brain lipids, suggesting an effective acylation mechanism that proceeds irrespective of the impaired blood flow. After a short restriction period (5 min), the radioactivity in diacylglycerol was elevated by 50%. After a longer restriction period (20 min), the radioactivity in the free fatty acid and diacylglycerol fractions increased to values of 130 and 87%, respectively. Polyphosphoinositides prelabeled with either [3H]ArA or 32P were rapidly degraded after 5 min of ischemia. After 20 min, the decrease in phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate radioactivity was 47 and 70%, respectively. Double labeling of phospholipids with [14C]palmitic acid and [3H]ArA indicated a preferential loss of [3H]ArA within the polyphosphoinositide species after 20 min, but not after 5 min of ischemia. The specific activity of [14C]palmitate remained unchanged. The current data suggest phospholipase C-mediated diacylglycerol formation at the beginning of the insult followed by a phospholipase A2-mediated ArA liberation at a later time, both enzymes presumably acting preferentially on polyphosphoinositide species.
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PMID:Generation of arachidonic acid and diacylglycerol second messengers from polyphosphoinositides in ischemic fetal brain. 132 30

Regional cardiac free fatty acid metabolism of 41 patients with coronary artery disease (CAD) and of 10 controls with normal coronary arteries was studied by means of I-123 phenylpentadecanoic acid (IPPA), a radioiodinated palmitic acid analog, and sequential single photon emission tomography (SPECT). All patients and controls underwent symptom--limited bicycle exercise, with the tracer being injected at peak stress. More than 99% of left ventricular segment of controls showed homogeneous tracer uptake and release, indicating homogeneous free fatty acid turnover in normal myocardium. Homogeneous postexercise uptake was followed by decreasing segmental activity in 75.1% of normally perfused segments in patients with CAD. Sixty-five percent and 88.6% of segments, assigned to the perfusion bed of 50%-75% and greater than 75% obstructed vessels had decreased IPPA release and/or reduced IPPA uptake. Patients with exercise induced ischemia had focal metabolic abnormalities in jeopardized myocardium for significantly longer time than clinical or electrocardiographic signs of ischemia (p less than 0.01). All patients with CAD and a negative stress test had metabolic abnormalities, but exhibited, compared to ECG--positive patients, less pronounced segmental metabolic aberrations. These findings indicate reduced cardiac utilization and delayed oxidation of IPPA, associated with exercise-induced ischemia in CAD. The metabolic changes suggest a marked sensitivity to ischemia as well as prolonged postischemic abnormalities of cardiac fatty acid metabolism in jeopardized myocardium.
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PMID:[Reduced myocardial fatty acid utilization in coronary heart disease following symptom limited ergometric stress. Detection of pathologic metabolic patterns using iodine-123-phenylpentadecanoic acid and sequential SPECT]. 278 61

The cardioprotective effects of an antilipolytic compound, nicotinic acid, on arrested-reperfused myocardium were investigated in the isolated in situ pig heart preparation. Hearts were preperfused for 15 min in the presence of (5-3H)-glucose and (U-14C)-palmitic acid. Half of the hearts were then perfused with 0.08 mM nicotinic acid for an additional 15-min period, while the remaining control hearts received unmodified perfusion. Arrest was then induced in all animals for 2 h using hypothermic K+ cardioplegia, followed by 60 min of normothermic reperfusion. In control hearts, there were significantly greater levels of long-chain acyl Co-A and acyl carnitine and lower levels of membrane phospholipids than in the nicotinic acid group. While nicotinic acid inhibited beta-oxidation during pre-ischemia and reperfusion, it also prevented the degradation of membrane phospholipids. The net result was a reduction of free fatty acid accumulation during arrest and reperfusion in the nicotinic acid group. Glycolysis, as reflected in 3H2O production, was significantly increased by nicotinic acid administration. In the control heart as compared to the nicotinic acid group, the incorporation of 14C-label from palmitate into triglyceride and cholesterol during arrest was enhanced, while incorporation into phospholipids was depressed. The cardioprotective effects of nicotinic acid were demonstrated by decreased release of creatine kinase and improved coronary blood flow, and cardiac contractility in the reperfused myocardium supplemented with nicotinic acid compared to the control group. These results suggest that nicotinic acid significantly protects the arrested-reperfused myocardium by a) preventing elevation of myocardial fatty acid levels, b) stimulating glycolysis by limiting fatty acid oxidation, c) inhibiting degradation of membrane phospholipids, and d) preventing accumulation of fatty acid metabolites with harmful detergent properties.
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PMID:Enhanced myocardial preservation by nicotinic acid, an antilipolytic compound: mechanism of action. 292 8

The mode of free fatty acid (FFA) liberation from the mouse brain during ischemia was investigated at various times after decapitation and under nizofenone treatment. Normal nonischemic brain FFAs consist mainly of palmitic acid (16:0), stearic acid (18:0), and oleic acid (18:1) with smaller amounts of arachidonic acid (20:4), docosahexaenoic acid (22:6), and others. Postdecapitative ischemia induced a rapid, biphasic release of 20:4 after a short lag of less than 30 s. The first phase showed a rapid 6.4-fold increase within 1 min of decapitation, followed by the second phase involving a slow release at less than one-fifth the rate of the first phase and lasting for at least 10 min. A similar, but not so marked, biphasic liberation was observed with 18:0. However, all of the other fatty acids (16:0, 18:1, 22:6, and others) were released only in a single phase at a slow rate. The time course for the rapid and specific liberation of 20:4 coincided with the time course for the decrease in brain ATP concentration during ischemia. Pretreatment of the animals with nizofenone resulted in a marked suppression of both FFA liberation and ATP depletion during ischemia. This suppression was particularly noteworthy with 20:4 and 18:0. The present study indicates that there is a specific and rapid liberation of 20:4 and 18:0 in a very early stage of ischemia and that this liberation seems to depend on availability of ATP in the brain. The physiological role of this transient 20:4 liberation during ischemia is discussed.
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PMID:Biphasic liberation of arachidonic and stearic acids during cerebral ischemia. 298 9

Although it is known that arachidonic acid accumulates in the ischemic myocardium and that cardiac prostaglandin formation from the precursor arachidonic acid is altered during disease states, the role of arachidonic acid in the myocyte itself is not yet clear. Using isolated Ca-tolerant adult rat heart muscle cells, we were able to study cardiac metabolism of arachidonic acid without the effects induced by endothelial or other non-muscle tissue. Myocytes rapidly incorporate arachidonic acid as well as other fatty acids into their lipid pools, the predominant acceptor being the triacylglycerols at an extracellular fatty acid concentration of 20 microM. As exogenous arachidonic acid is decreased, the distribution pattern shifts to favor phospholipid esterification. Cardiocyte prostaglandin production from arachidonic acid added to the incubation medium was limited (less than 1% conversion of added arachidonic acid) and lipoxygenase pathway activity was not detected. Oxidation rates of arachidonic acid were 3-fold lower than for palmitic acid, indicating that it is of secondary importance in energy-yielding reactions. Our results suggest that arachidonic acid serves primarily as a structural component of myocardial membranes and that its release during ischemia would permit its use as a substrate for prostaglandin production by coronary vascular tissue.
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PMID:The role of arachidonic acid in rat heart cell metabolism. 311 4

Using the four-vessel extracranial one staged occlusion model of adult Wistar rats, we analyzed quantitatively released free fatty acids during ischemia. Also have we analyzed the effect of bifemelane to reduce free fatty acid accumulation after the onset of ischemia. Bifemelane (15 mg/kg, 30 mg/kg) and saline as control were intraperitoneally administered to adult Wistar rat prior to 30 minutes of experimentally induced ischemia. The results obtained were analyzed by one or two way analysis of variance (ANOVA). Physiological variables (systemic arterial pressure, PaO2, PaCO2, pH) did not change significantly in all four experimental groups. Total free fatty acid levels (sum of 5 fatty acid) increased significantly after ischemia (30 minutes). Higher dose (30 mg/kg) of bifemelane administration significantly reduced total free fatty acid accumulation, though lower dose (15 mg/kg) did have no effect. Bifemelane (30 mg/kg) reduced significant accumulation in the amount of saturated and monounsaturated fatty acid (palmitic acid [16:0], stearic acid [18:0] and oleic acid [18:1]). Arachidonic (20:4) and docosahexaenoic (22:6) acid failed to show any effective reduction by bifemelane pre-treatment of lower nor higher dose. Bifemelane is supposed to have many pharmacological effects such as increase in cerebral blood flow, augmentation of glucose uptake, monoamine metabolism, cerebral vasodilatation and platelet antiaggregation. Free fatty acid accumulation is effectively suppressed by the higher dose of bifemelane administration. Although the exact mechanism are not clearly identified by the result obtained in this experiment, selective inhibition of accumulation in saturated and monounsaturated fatty acids by bifemelane pretreatment may be obtained by the improvement of energy metabolism, which may help to reacylation of fatty acid into phospholipid.
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PMID:[Effects of bifemelane on the free fatty acid levels during ischemia]. 321 39

In addition to radionuclide ventriculography and thallium scintigraphy, already well established in nuclear medicine, assessment of myocardial metabolism is also of interest for diagnosis and follow-up observations in heart disease. Under aerobic conditions and in the fasting state, the heart muscle primarily oxidizes fatty acids; during ischemia, in contrast, there is slowing of fatty acid turnover and increased anaerobic glycolysis. With 11C-palmitic acid, in humans, reduced fatty acid uptake has been documented in infarcted myocardial regions. The analysis of 11C-palmitic acid in dogs showed a three-phased elimination curve in normal myocardium. In ischemic myocardium, there was diminished utilization of free fatty acids and the glucose utilization was concomitantly increased. After insulin-glucose infusion, as well, there was increased glucose utilization and a reduction in fatty acid utilization. Studies with 11C-palmitic acid require the equipment for positron emission tomography (PET); because of the short half-life of 20.3 minutes, the nuclide must be generated by a cyclotron in the immediate vicinity. In the search for well-suited isotopes for use in planar scintigraphy employing a gamma camera, the uptake and elimination of a variety of isotopically-marked fatty acids were measured and compared with the characteristics of 14C-palmitic acid. For 17-123I-heptadecanic acid (IHA) the elimination curve was similar to that of 14C-palmitate: disadvantage, however, was the relatively high percentage of water soluble marked catabolites which required dual parameter analysis by means of 99-m-technetium pertechnetate or 123I sodium iodide to quantify the amount of myocardial fatty acid utilization through subtraction of the externally measured water soluble catabolite from the externally measured total activity. In studies with the gamma camera in fasting patients in whom 2 to 3 mCi IHA was injected intravenously after symptom limited bicycle ergometry, in healthy subjects the elimination halftime for the first rapid phase was 24.4 +/- 4.7 minutes. Patients with angiographically-documented coronary artery disease, in the afflicted myocardial segments, had diminished fatty acid uptake and prolonged elimination halftime as compared with normally perfused segments. In patients with dilated cardiomyopathy there was an inhomogeneous distribution of activity in the myocardium and, in contrast to coronary artery disease, a discordance between local fatty acid uptake and turnover rate. After chronic and acute alcohol consumption there were comparable findings which were shown to be reversible after several weeks of abstinence.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Planar scintigraphy versus PET in measuring fatty acid metabolism of the heart]. 349 62

Gerbil forebrains were frozen in situ to inactivate the tissues, and 1,2-diacylglycerols were first measured quantitatively by HPLC. Although 1,2-diacylglycerols were completely recovered from the HPLC column, the control amount of 1,2-diacylglycerol in gerbil forebrain was only 79.6 nmol/g wet weight, which is about one-fourth of that previously reported for gerbil brain inactivated by liquid N2 after decapitation instead of in situ freezing. The fatty acid composition of 1,2-diacylglycerols in gerbil forebrain was first reported and the control 1,2-diacylglycerols were richer in palmitic acid than in stearic acid or arachidonic acid, which is rather different from the data previously reported for mouse or rat brain obtained by decapitation and analyzed by traditional TLC methods. The amount of 1,2-diacylglycerol increased by 82.9% in gerbil forebrain during 5 min of ischemia induced by bilateral carotid ligation. Arachidonic acid and stearic acid were abundant in the 1,2-diacylglycerols produced by 5 min of ischemia. Thus we were able to obtain accurate values of the amount and the fatty acid composition of 1,2-diacylglycerols in gerbil forebrains using HPLC and in situ freezing technique.
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PMID:Accurate evaluation of 1,2-diacylglycerol in gerbil forebrain using HPLC and in situ freezing technique. 373 96

Positron emission tomography allows noninvasive assessment of myocardial blood flow and metabolism, and may aid in defining the extent and severity of an ischemic injury. This hypothesis was tested by studying, in chronically instrumented dogs, regional blood flow and metabolism during and after a 3 hour balloon occlusion of the left anterior descending coronary artery. The metabolic findings after ischemia were compared with the recovery of regional function over a 4 week period. N-13 ammonia was used as a blood flow tracer, and C-11 palmitic acid and F-18 deoxyglucose as tracers of fatty acid and glucose metabolism, respectively. Regional myocardial function was monitored with ultrasonic crystals implanted subendocardially. Regional function improved most between 24 hours and 1 week after reperfusion, but was still attenuated at 4 weeks. The slow functional recovery was paralleled by sustained metabolic abnormalities, reflected by segmentally delayed clearance of C-11 activity from myocardium and increased uptake of F-18 deoxyglucose. Absence of blood flow and C-11 palmitic acid uptake at 24 hours of reperfusion correlated with extensive necrosis as evidenced by histologic examination. Conversely, uptake of C-11 palmitic acid with delayed C-11 clearance and increased F-18 deoxyglucose accumulation identified reversibly injured tissue that subsequently recovered functionally and revealed little necrosis. Thus, recovery of metabolism after 3 hours of ischemia is slow in canine myocardium and paralleled by slow recovery of function. Metabolic indexes by positron tomography early after reperfusion can identify necrotic and reversibly injured tissue. Positron tomography may therefore aid in defining the extent and prognosis of an ischemic injury in patients undergoing reperfusion during evolving myocardial infarction.
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PMID:Sustained regional abnormalities in cardiac metabolism after transient ischemia in the chronic dog model. 387 92


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