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

Exogenous fructose 1,6-diphosphate (FDP), a glycolytic intermediate, has recently been demonstrated to accelerate ATP production, prevent glycogen breakdown, stimulate glycogen synthesis, and synthesize free fatty acids in animals and humans. To assess the effects of FDP on the hormonal and metabolic response to exercise, ten trained males (34 +/- 7 yr) underwent 1 h of continuous exercise at 70% VO2max followed by 20 W.min-1 increments to exhaustion. Two hundred fifty mg.kg-1 body weight FDP or placebo was infused in randomized, double-blind, crossover fashion. No differences were observed in heart rate, blood pressure, gas exchange data, perceived effort, or glucose, insulin, free fatty acid, lactate, beta-hydroxybutyrate, glycerol, and glucagon concentration at rest, during exercise, or upon exhaustion. In contrast to the previously reported bioenergetic effects of FDP under conditions in which glycolysis is impeded (acidosis, hypoxia, and ischemia), FDP did not affect the gas exchange, hormonal, or substrate response to moderately high intensity exercise in healthy normals.
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PMID:Effect of fructose 1,6-diphosphate infusion on the hormonal response to exercise. 240 38

We investigated the mechanism of membrane phospholipid degradation during reperfusion of ischemic myocardium using isolated and perfused rat hearts. Thirty min of myocardial reperfusion after 30 min of normothermic global ischemia resulted in a significant decrease of phosphatidylcholine (PC) content associated with a small but significant increase in lysophosphatidylcholine (LPC) content. Myocardial ischemia for up to 60 min caused no significant loss of any of the major phospholipids. Isotopic incorporation of [14C]arachidonic acid (AA) as well as [3H]-glycerol into PC was significantly attenuated in the ischemic-reperfused heart compared with the normally perfused heart, suggesting that both reacylation and de novo pathways for PC synthesis were inactivated during reperfusion. In the heart prelabeled with [14C]AA, the radiolabeled PC was decreased significantly during reperfusion, associated with a small but significant increase in [14C]AA accumulation. The decreases of PC content and incorporation of [14C]AA into PC, as well as the increases of LPC content and the [14C]AA during reperfusion, were prevented by reperfusion with low Ca2+ (50 microM) buffer or by pretreatment with trifluoperazine (10 microM) or mepacrine (50 microM), but not with verapamil (1 microM). The inhibition of loss of PC was associated with significant diminution of creatine kinase release from the reperfused hearts. The present study indicates that the net loss of membrane phospholipids, especially with respect to PC during reperfusion, may result from 1) inhibition of reacylation of AA, 2) inhibition of de novo synthesis, and 3) stimulation of phospholipase activity. These results are consistent with an influx of Ca2+, although other interpretations are also possible.
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PMID:Mechanism of membrane phospholipid degradation in ischemic-reperfused rat hearts. 250 30

In 50 patients with angiographically proven coronary artery disease (CAD) and typical angina pectoris, and in 35 patients with normal angiographic findings the amplitudes of R-waves (sigma R) in 36 precordial ECG leads were measured before and after application of 0.8 mg glycerol trinitrate (GTN). In 21 patients the examination was repeated after coronary bypass surgery. In the CAD-patients decrease of sigma R was shown after sublingual GTN: 19.5 +/- 26.4 mm (p less than 0.05). The control group showed a slight increase of sigma R: 18.7 +/- 16.2 mm (p less than 0.05). After bypass surgery the decrease of sigma R after glycerol trinitrate could no longer be shown. These result support the hypothesis that glycerol trinitrate is capable of reducing enhanced R-amplitudes in resting ECG due to ischemia.
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PMID:[Effect of glycerol trinitrate on R-amplitude in patients with chronic ischemic heart disease]. 251 82

More efficient methods of islet isolation must be developed for islet transplantation to become clinically routine. During collagenase dispersal of human pancreas, an amorphous, viscous, gellike material often develops and entraps large numbers of islets, thereby reducing the yield. When donor human pancreas is minced and treated with collagenase, the gel forms most abundantly if the digestion temperature is less than 35 degrees C and if pH falls below 7.2 +/- 0.2. Gel formation appears to be proportional to warm- or cold-ischemia time and may be related to tissue trauma during collection. Once gel has formed, trapped islets cannot be released by filtration, dilution, DNase, incubation temperature, or pH adjustment. These characteristics suggest that the material is gelatin derived from collagen released enzymatically from pancreatic stroma. We demonstrate that gelation is greatly reduced or eliminated when 1) the incubation medium includes glycerol--a common gelatin solvent--at 5% (vol/vol), 2) the minced tissue-to-total incubation volume ratio is greater than or equal to 1:10, 3) free-islet exposure to pancreatic digestion products is minimized by frequent separation of islets, and 4) collagenase concentration is optimized by titration. Gelation is also minimized by maintaining 5) incubation temperature at 38 +/- 1 degree C and 6) pH in the range 7.7-7.9. Variations in these physical and chemical conditions were analyzed by determining islet yields (stereoscopic microscope counts of serially diluted samples) and by insulin radioimmunoassay of acid alcohol extracts of isolated islets after separation through discontinuous Ficoll gradients. When isolation conditions are optimized as stated, we typically recover 3.3 +/- 1.0 x 10(4) islets/g pancreas, corresponding to greater than 10(6) islets per donor.
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PMID:Factors influencing isolation of islets of Langerhans. 264 35

Fatty acids, the preferred substrate in normoxic myocardium, are derived from either exogenous or endogenous triacylglycerols. The supply of exogenous fatty acids is dependent of the rate of lipolysis in adipose tissue and of the lipoprotein lipase activity at the coronary vascular endothelium. A large part of the liberated fatty acids is reesterified with glycerol-3-phosphate and converted to triacylglycerols. Endogenous lipolysis and lipogenesis are intracellular compartmentalized multienzyme processes of which individual hormone-sensitive steps have been demonstrated in adipose tissue. The triacylglycerol lipase is the rate-limiting enzyme of lipolysis and glycerol-3-phosphate acyltransferase and possibly phosphatidate phosphohydrolase are the rate-limiting enzymes of lipogenesis. The hormonal regulation of both processes in heart is still a matter of dispute. Triacylglycerol lipase activity in myocardial tissue has two intracellular sources: 1. the endoplasmic reticular and soluble neutral lipase, and 2. the lysosomal acid lipase. Studies in our laboratory have indicated that whereas lipolysis is enhanced during global ischemia and anoxia, overall lipolytic enzyme activities in heart homogenates were not altered. In addition we were unable to demonstrate alterations in tissue triacylglycerol content and glycerol-3-phosphate acyltransferase activity under these conditions. Lipolysis, is subject to feedback inhibition by product fatty acids. Therefore all processes leading to an increased removal of fatty acids from the catalytic site of the lipase will stimulate lipolysis. These studies will be reviewed. In addition, studies from our department have demonstrated the capacity of myocardial lysosomes to take up and degrade added triacylglycerol-particles in vitro. Such a process, stimulated by Ca2+ and stimulated by acidosis, offers another physiological target for hormone actions.
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PMID:Hormones and triacylglycerol metabolism under normoxic and ischemic conditions. 267 63

We studied lipolysis in the isolated rat heart, measured as glycerol release during anoxia, low-flow ischemia and subsequent reperfusion. It was found that the rate of lipolysis was enhanced during ischemia/anoxia while the lipase activities in tissue extracts involved in the myocardial lipolysis and the amount of triglycerides were not affected. This indicates the dominant occurrence of a lipolysis-reesterification principle in ischemic and anoxic tissue. A common observation of ischemia/anoxia is an increase in the tissue NADH/NAD+ ratio. Therefore we investigated the effect of lactate and malate, both of which enhance the tissue redox state on myocardial lipolysis. Perfusion in the presence of lactate (10 mM) and malate (10 mM) both stimulated myocardial lipolysis by about five times. This suggests that the rate of reesterification of product fatty acids to triglycerides, which is determined by the NADH/NAD+ ratio, because of the increased formation of glycerol 3-phosphate from dihydroxy acetone phosphate, plays an important role in the regulation of lipolysis. The existence of triglyceride-fatty acid-triglyceride cycle is discussed.
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PMID:Enhanced lipolysis of myocardial triglycerides during low-flow ischemia and anoxia in the isolated rat heart. 273 May 23

Preincubation of rat myocardial cells in hypoxic substrate-free Krebs-Ringer bicarbonate buffer (pH 7.4, 37 degrees C) resulted in a substantial decline in high energy phosphates (ATP and CP). Thus, 20 and 60 min preincubation produced a 18 and 72% decline in ATP content, whereas the parallel decline in CP content was 51 and 73%. This energy depletion was accompanied by a change in cell morphology from the initial rod-shaped form to rounded up (hyper-contracted) myocytes. In cells preincubated in substrate-free normoxic buffer, both normal morphology and energy homeostasis were maintained. When energy depleted myocytes later were incubated in the presence of phospholipase C (PLC), this resulted in a substantial release of glycerol, amounting to 92 and 137 nmol/10(6) cells.2 h in 20 and 60 min energy depleted myocytes, respectively. In addition, PLC caused an increased leakage of lactate dehydrogenase in energy depleted myocytes. Normal cells, on the other hand, were apparently not affected by PLC. These data suggest that PLC selectively attacks energy depleted and/or structurally damaged myocytes. This could well enhance the breakdown of the natural barrier between the extra- and intracellular compartments and thus augment the cellular damage during ischemia. Moreover, energy depleted myocytes appeared exceptionally sensitive to this enzyme, since the levels required to cause glycerol or lactate dehydrogenase release were several orders of magnitude lower than that required to cause membrane permeation in other cell types.
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PMID:Phospholipase C-evoked glycerol release in energy depleted rat myocardial cells. 277 31

Disturbances in lipid metabolism may play an important role in the onset of irreversible myocardial damage. To investigate the effect of ischemia and reperfusion on lipid homeostasis and to delineate its possible consequences for myocardial damage, Krebs-Henseleit-perfused, working rat hearts were subjected to various periods of no-flow ischemia (10 to 90 minutes) with or without 30 minutes of reperfusion. During ischemia, the rise in nonesterified fatty acids (NEFAs) was preceded by the accumulation of substantial amounts of glycerol, indicating the presence of an active triacylglycerol-NEFA cycle. The subsequent rise in NEFAs (from 0.25 to 1.64 mumol/g dry residue wt after 90 minutes [means]) coincided with the reduction of ATP to values lower than 10 mumol/g dry wt and the rise of AMP, a potent inhibitor of acyl-coenzyme A synthetase, to values exceeding 2 mumol/g dry wt, making the latter compound a good candidate to hamper the turnover of endogenous lipids during prolonged ischemia. Reperfusion resulted in an additional rise in NEFAs (up to 4.1 mumol/g dry residue wt after 60 minutes of ischemia). Neither ischemia nor reperfusion resulted in significant decreases in the tissue content of triacylglycerols and the various phospholipids. During reperfusion recovery of stroke volume was still adequate at tissue NEFA levels thought to be incompatible with normal mitochondrial function. A positive correlation (r = 0.81) was found between NEFA content of reperfused hearts and cumulative release of lactate dehydrogenase during reperfusion. Accordingly it is concluded that 1) reperfusion results in additional changes in myocardial lipid homeostasis, 2) the accumulating NEFAs are compartmentalized, possibly at the cellular level, and 3) the accumulation of NEFAs is a sensitive marker for myocardial cell damage.
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PMID:Lipid alterations in isolated, working rat hearts during ischemia and reperfusion: its relation to myocardial damage. 278 64

In this study, we examined phosphoinositide metabolism during ischemia and reperfusion using an isolated and perfused rat heart. When myocardial phosphoinositides were prelabeled with [3H]inositol, reperfusion after 30 minutes of normothermic global ischemia resulted in significant accumulations of radiolabeled inositol phosphate, inositol bisphosphate, and inositol trisphosphate. Isotopic incorporation of [3H]inositol into phosphatidylinositol, phosphatidylinositol-4-phosphate, and phosphatidylinositol-4,5-bisphosphate was increased significantly in the heart reperfused with [3H]inositol after 30 minutes of ischemia compared with that perfused with [3H]inositol after 30 minutes of nonischemic perfusion. However, isotopic incorporation of [3H]glycerol into diacylglycerol, phosphatidic acid, and all of the three phosphoinositides was diminished in the reperfused hearts. Reperfusion of the ischemic heart prelabeled with [14C]arachidonic acid resulted in significant increases in [14C]diacylglycerol and [14C]phosphatidic acid. The enhanced accumulations of [3H]inositol phosphates during reperfusion were not affected by treatment with prazosin plus atropine or indomethacin, but were inhibited by hypoxic reperfusion, reperfusion with Ca2+-free buffer, or by mepacrine. These results suggest that myocardial reperfusion stimulates phosphodiesteratic breakdown and turnover of phosphoinositides, and increased Ca2+ influx caused by reperfusion may be involved in the mechanism of stimulation of phosphatidylinositol-specific phospholipase C activity in the rat heart.
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PMID:Enhanced phosphodiesteratic breakdown and turnover of phosphoinositides during reperfusion of ischemic rat heart. 284 1

The recent discovery of neutral active choline and ethanolamine glycerophospholipid specific phospholipase C in myocardium (Wolf RA, Gross RW. J Biol Chem 1985;260:7295) has demonstrated a novel catabolic pathway that potentially contributes to the accumulation of amphiphilic metabolites during myocardial ischemia. To assess the potential importance of this pathway, we quantified the temporal course of alterations in myocardial 1-0-alk-1'-enyl-2-acyl-sn-glycerol (AAG) and 1,2-diacyl-sn-glycerol (DAG) content during control and ischemic intervals in an isolated perfused Langendorf model. AAG accumulated over fivefold to 8.70 and 18.27 nmol/g dry in 20- and 60-minute ischemic rabbit hearts, respectively (p less than 0.02). The only AAG molecular species that was detected in substantial amounts in control or ischemic rabbit hearts was 1-0-hexadec-1'-enyl-2-acyl-sn-glycerol. Since this molecular species is enriched in plasmenylcholine these findings suggest that AAG production is likely mediated by phospholipase C-catalyzed hydrolysis of plasmenylcholine. In contrast to ischemia-induced AAG accumulation, DAG content decreased during both control and globally ischemic perfusion intervals. In summary, these findings demonstrate that AAG, in contrast to DAG, accumulates during myocardial ischemia indicating that at least some metabolites of plasmalogen and diacyl phospholipids accumulate at differential rates during myocardial ischemia.
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PMID:Differential accumulation of diacyl and plasmalogenic diglycerides during myocardial ischemia. 290


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