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 aim of this study was to investigate the efficacy of HTK solution for cardioplegia in the continuous 120-minute cross-clamping method in comparison with the conventional GIK method. In an experimental model, the efficacy of ketoglutarate and tryptophan in recovering cardiac function after 6 hours' preservation was evaluated. In Group A, in which ketoglutarate was excluded from the HTK solution, percent developed pressure was significantly decreased (p<0.01) and the released enzyme (CK-MB) was significantly increased, but coronary flow was not significantly changed. In Group B, in which tryptophan was excluded from the HTK solution, a significant decrease in percent developed pressure and coronary flow was seen (p<0.01). This indicated that ketoglutarate and tryptophan were effective in protecting the myocardium during the ischemia. In the clinical study, 54 open heart operations were performed with cardioplegic solution, using either HTK solution or GIK solution. In the HTK Group, the heart was exposed to 120 minutes' of ischemia after the infusion of HTK solution (3L). In the GIK group, intermittent GIK perfusion was performed every 30 minutes in association with continuous cold blood perfusion. Percent fraction shortening and cardiac index were not significantly different. However, CK-MB and HBDH were increased in the GIK group, postoperatively. Histological findings showed deterioration of the mitochondria and myocytes during ischemia in the GIK group. These data suggest that the effect of the cardioplegias in heart preservation was satisfactory in both groups, although the interval of intermittent perfusion was prolonged to 120 minutes in the HTK solution.
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PMID:Effect of HTK solution for myocardial preservation. 869 63

DL-1,3-butanediol (DL-BD) is an ethanol dimer which affords cerebral protection in various experimental models of hypoxia and ischemia but its mechanism of action is unknown. DL-BD is a ketogenic alcohol and it has been proposed that its protective effect was accomplished through cerebral utilization of ketone bodies. Since DL-BD is a racemic, its metabolic effects could be due to D, L or both isomers. The effects of equimolar doses of DL-, D- and L-BD (25 mmol/Kg) on cerebral metabolism were studied by measuring the cortical levels of the main glycolytic (glycogen, glucose, glucose 6-phosphate, fructose 1,6-diphosphate, pyruvate and lactate) and citric acid cycle (citrate, alpha-ketoglutarate and L-malate) intermediates. The two BD isomers exerted different effects on cerebral metabolism. Unlike L-BD, D- and DL-BD treatments resulted in a slight (+10%) but significant increase in citrate level whereas L-BD treatment led to significant reduction in pyruvate (-12%) and lactate (-24%) levels. These effects were apparently not linked to hyperketonemia, since DL-BHB treatment, which mimicked hyperketonemia induced by DL-BD, had no effect on cerebral metabolites but might be due to intracerebral metabolism of BD.
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PMID:Effect of D- and L-1,3-butanediol isomers on glycolytic and citric acid cycle intermediates in the rat brain. 884 93

Fructose-1,6-bisphosphate (FBP), an intermediate of glucose metabolism, is neuroprotective in brain hypoxia or ischemia. Because the mechanisms for this protection are not clear, we examined the effects of FBP on two important events in brain ischemia, i.e., loss of ATP and release of the excitatory neurotransmitter glutamate. Glutamate release from cortical brain slices was measured fluorometrically (glutamate dehydrogenase-catalyzed conversion of glutamate to alpha-ketoglutarate) during hypoxia (PO2 15 mm Hg) or hypoxia plus 100 microM cyanide. FBP (3.5 mM, with glucose 20 mM) reduced glutamate release during hypoxia by 55% and during hypoxia/cyanide by 46% (p < 0.005), and prevented a significant fall in [ATP]. [ATP] was maintained in oxygenated glucose-free conditions with 20 but not 3.5 mM FBP, and fell to < 20% of normal with hypoxia. Despite the drop in [ATP], 3.5 or 20 mM FBP without glucose decreased hypoxia-evoked glutamate release. We conclude (1) FBP present without glucose preserves normal [ATP] only when oxygen is available, suggesting limited uptake and metabolism; and (2) FBP decreases hypoxia-evoked glutamate release by processes independent of [ATP]. These results suggest protective actions of FBP that are separate from augmentation of anaerobic energy production, as previously proposed.
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PMID:Effects of fructose-1,6-bisphosphate on glutamate release and ATP loss from rat brain slices during hypoxia. 885 28

In this study, the short-term outcome of renal transplants from non-heart-beating donors (NHBD) preserved by machine perfusion (MP) is evaluated and compared to preservation by cold storage (CS). Twenty-two NHBD kidneys were procured during 1993 and 1994 after in situ perfusion with histidine-tryptophan ketoglutarate and preserved by continuous perfusion using University of Wisconsin organ preservation solution for MP as a perfusate. Between 1980 and 1992, 57 NHBD kidneys were procured and preserved by CS. Donors in the MP group sustained increased first warm ischemia times (WIT1) (P < 0.1) and recipients in the MP group suffered longer anastomosis time, worse HLA-DR mismatch, and more initial use of cyclosporin as immunosuppressant; all these factors are known to be deleterious to short-term outcome. Despite these unfavorable conditions, delayed function (DF) rate was decreased in the MP group, although not significantly. However, when considering only kidneys with WIT1 > or = 45 min, short-term outcome was significantly better in the MP group (P < 0.05). We conclude that MP is superior for the preservation of NHBD kidneys, especially after prolonged warm ischemia.
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PMID:Short-term outcome of kidney transplants from non-heart-beating donors after preservation by machine perfusion. 895 96

This study investigates firstly how far cellular edema correlates with parameters of the anaerobic energy turnover independent of the method used for cardiac arrest, and secondly to what extent cellular edema developing during reversible global ischemia is reduced after reperfusion. Canine hearts were arrested 1. by aortic cross clamping (ACC), 2. by coronary perfusion with St. Thomas solution, or 3. HTK (histidine tryptophan ketoglutarate) solution (Custodiol). Samples for biochemical and structural analysis were taken at different times during ischemia and after reperfusion with Tyrode solution. Cellular edema determined morphometrically and given as volume ratio of sarcoplasm and mitochondria to myofibrils (Vvsp + V vmi/Vvmf) varies significantly in the differently arrested hearts. Reperfusion after a decrease in ATP to 4 mumol/gww (revival time) leads to a nearly complete structural recovery. The relationship between cellular edema and defined over-all metabolite tissue concentrations and extracellular pHe values shows: 1. during the decrease of creatine phosphate to 3 mumol/gww, cellular edema does not change; it is, however, significantly higher after ACC and St. Thomas than after HTK perfusion; 2. at each lactate concentration, cellular edema differs significantly depending on the form of cardiac arrest; 3. during the decrease of ATP and pHe cellular edema increases and is comparable at concentrations < 4 mumol/gww and at pHe values < 6.5 independent of the form of cardiac arrest; 4. beyond 10 mumol/gww of inorganic phosphate (Pi), increasing values for cellular edema correspond to defined Pi values in the differently arrested hearts. Thus, the ratio VVSp+ VVMi/VVMf is a powerful parameter for the determination of cellular edema during ischemia, as well as for correlations with metabolic parameters.
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PMID:Cellular edema and alterations in metabolite content in the ischemic and reperfused canine heart following different forms of cardiac arrest. 912 37

To examine metabolic regulation in postischemic hearts, we examined oxidative recycling of 13C within the glutamate pool (GLU) of intact rabbit hearts. Isolated hearts oxidized 2.5 mmol/L [2-13C]acetate during normal conditions (n = 6) or during reperfusion after 10 minutes of ischemia (n = 5). 13C-Nuclear magnetic resonance spectra were acquired every 1 minute. Kinetic analysis of 13C incorporation into GLU provided both tricarboxylic acid (TCA) cycle flux and the interconversion rate (F1) between the TCA cycle intermediate, alpha-ketoglutarate (alpha-KG), and the largely cytosolic GLU. The rate-pressure product in postischemic hearts was 46% of normal (P < .05). No difference in substrate utilization occurred between groups, with acetate accounting for 92% of the carbon units entering the TCA cycle at the citrate synthase step. TCA cycle flux in postischemic hearts was normal (normal hearts, 10.7 mumol.min-1.g-1; postischemic hearts, 9.4 mumol.min-1.g-1), whereas F1 was 72% lower at 2.9 +/- 0.4 versus 10.2 +/- 2.5 mumol.min-1.g-1 (mean +/- SE) in normal hearts (P < .05). From additional hearts perfused with 2.5 mmol/L [2-13C]acetate plus supplemental 5 mmol/L glucose, any potential differences in endogenous carbohydrate availability were proved not to account for the reduced rate alpha-KG and GLU exchange, which remained depressed in postischemic hearts. However, specific activities of the transaminase enzyme, catalyzing chemical exchange of alpha-KG and GLU, were the same, and transaminase flux was 100 mumol.min-1.g-1 in postischemic hearts versus 68 mumol.min-1.g-1 in normal hearts. Normal transaminase activity and the increased flux in postischemic hearts are contrary to the reduced F1. The findings indicate reduced metabolite transport rates across the mitochondrial membranes of stunned myocardium, particularly through the reversible alpha-KG-malate carrier.
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PMID:Altered metabolite exchange between subcellular compartments in intact postischemic rabbit hearts. 924 77

Warm ischemia is known to induce substantial damage to the liver parenchyma. With respect to clinical liver transplantation, the tolerance of the liver to warm ischemia and the preservation of these organs have not been studied in detail. In isolated reperfused pig livers we proceeded according to the following concept: Livers were subjected to 1 or 3 h of warm ischemia. Subsequently, these organs were preserved by either normothermic perfusion or cold storage (histidine-tryptophan-alpha-ketoglutarate, HTK) for 3 h each. After storage, liver function was assessed in a reperfusion circuit for another 3 h. Parameters under evaluation were bile flow, perfusion flow, oxygen consumption, enzyme release into the perfusate (creatine kinase, glutamic oxaloacetic transaminase (GOT), lactic dehydrogenase, and glutamic pyruvic transaminase), and histomorphology. Damage to the liver was lowest after warm ischemia of 1 h. The results after cold storage were superior to those after normothermic perfusion (GOT: 3.2 +/- 0.3 and 2.6 +/- 0.2 U/g liver; cumulative bile production: 14.7 +/- 2.1 and 9.4 +/- 1 ml, respectively; P < 0.05). In contrast, we found substantial damage at the end of reperfusion in livers undergoing 3 h of warm ischemia under both preservation techniques with severe hepatocellular pyknoses and essentially altered nonparenchymal cells. The results suggest that pig livers undergoing 1 h of warm ischemia and cold storage for 3 h with HTK solution may lead to functioning after transplantation.
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PMID:Preservation of pig liver allografts after warm ischemia: normothermic perfusion versus cold storage. 939 99

It was the aim of the present study to investigate the influence of Bretschneider's cardioplegia on norepinephrine (NE) release [determined by high pressure liquid chromatography (HPLC) and electrochemical detection] in isolated perfused guinea-pig hearts. The following resulted were noted. (1) Calcium-dependent exocytotic NE release evoked by electrical field stimulation (12 Hz, 1 min) was completely suppressed after only 3 min of normothermic (37.5 degrees C) Bretschneider's cardioplegia. (2) Stop-flow ischemia is associated with a substantial calcium-independent, non-exocytotic NE release, which is regarded as a sodium-dependent carrier-mediated process. Accordingly, it is inhibited by blockers of the sodium/proton-exchanger (e.g. amiloride) and the neuronal uptake1-carrier (e.g. desipramine). Compared with stop-flow ischemia alone, cardioplegia with 3 min of Bretschneider's histidine-tryptophan-ketoglutarate (HTK)-solution preceding stop-flow enhanced NE release at all stop-flow durations (10-90 min) investigated (e.g. after 30 min of normothermic Bretschneider's cardioplegia: 1070+/-41 pmol/g, n = 45, v stop-flow alone: 764+/-48 pmol/g, n = 27, P<0.05). The NE concentrations determined in the cardiac effluent upon reperfusion followed a typical first order kinetic indicating that the transmitter release had already occurred during stop-flow. Hypothermia reduced NE release in a temperature-dependent manner down to intramyocardial temperatures of 2 7.5 degrees C. NE release evoked by Bretschneider's cardioplegia still exceeded that induced by stop-flow ischemia alone by up to 60%. The NE release evoked by Bretschneider's cardioplegia and stop-flow ischemia was calcium-independent. However, it was significantly reduced by desipramine and amiloride, but both agents had a more pronounced inhibitory effect on NE release evoked by stop-flow ischemia alone. (3) This difference may be due to an intrinsic effect of Bretschneider's HTK-solution, as continuous administration of normothermic Bretschneider's HTK-solution induced a substantial NE release which was neither calcium-dependent nor inhibited by blockade of either uptake1 or sodium/proton-exchange. It is concluded that Bretschneider's cardioplegia is not neuroprotective, as it even augments the stop-flow ischemia-induced nonexocytotic NE release.
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PMID:Influence of Bretschneider's cardioplegia on norepinephrine release from isolated perfused guinea-pig hearts. 1007 18

The transport of metabolites between mitochondria and cytosol via the alpha-ketoglutarate-malate carrier serves to balance flux between the two spans of the tricarboxylic acid (TCA) cycle but is reduced in stunned myocardium. To examine the mechanism for reduced transporter activity, we followed the postischemic response of metabolite influx/efflux from mitochondria to stimulation of the malate-aspartate (MA) shuttle. Isolated rabbit hearts were either perfused with 2.5 mM [2-13C]acetate (n = 7) or similarly reperfused (n = 5) after 10-min ischemia. In other hearts, the MA shuttle was stimulated with a high cytosolic redox state (NADH) induced by 2.5 mM lactate in normal (n = 6) or reperfused hearts (n = 7). In normal hearts, the MA shuttle response accelerated transport from 8.3 +/- 3.4 to 16.2 +/- 5.0 micromol. min(-1). g dry wt(-1). Although transport was reduced in stunned hearts, the MA shuttle was responsive to cytosolic NADH load, increasing transport from 3.4 +/- 1.0 to 9.8 +/- 3.7 micromol. min(-1). g dry wt(-1). Therefore, metabolite exchange remains intact in stunned myocardium but responds to changes in TCA cycle flux regulation.
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PMID:Mitochondrial transporter responsiveness and metabolic flux homeostasis in postischemic hearts. 1048 5

The quality of organ preservation is of major importance in minimizing the incidence of primary graft nonfunction and organ rejection. For this study a new semiquantitative score was developed that grades morphologic tissue alterations in the liver according to their frequency and severity. It was applied to assess commonly used perfusion solutions for their efficacy in preventing early and late tissue damage after rat liver transplantation. For transplantation the livers were stored in Euro-Collins (EC, group I; n = 11), histidine-tryptophan-alpha-ketoglutarate (HTK, group II; n = 11), or University of Wisconsin solution (UW, group III; n = 11). Rat liver transplantation was performed with graft arterialization by the method of Engemann. Biopsies were taken for morphological examination and semiquantitative scoring during the donor operation, after 4 h of cold storage, 1 h after reperfusion, and 4 weeks postoperatively. An immunohistological bromodeoxyuridine (BrdU) assay was also performed on the day of dissection to assess the rate of hepatic proliferation. Semiquantitative morphological analysis gave widely differing results in all experimental groups after 4 h of ischemia. There was less intracellular and interstitial edema, fatty degeneration, intralobular necrosis, and hepatocellular proliferation in the HTK group than in the other groups. Neither after cold ischemia nor 1 h after reperfusion did Kupffer-cell activation occur; this is known to play a major role in the development ofischemia and reperfusion injury. Furthermore, late changes such as bile-duct proliferation and vascular and sinusoidal alterations appeared less frequently in this group. The hepato-protective powers of HTK solution might therefore be due to decreased Kupffer-cell activation.
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PMID:Organ preservation with EC, HTK, and UW, solution in orthotopic rat liver transplantation. Part II. Morphological study. 1050 Oct 78


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