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)

Free arachidonic acid is released rapidly in the brain at the onset of ischemia and during convulsions. The transient nature of this phenomenon indicates the existence of an active reacylation system for this fatty acid, likely an arachidonoyl-CoA synthetase-arachidonoyl transferase. The first of these enzymatic activities in brain microsomes was studied and it was found that [1-14C]arachidonic acid is rapidly activated and shows an absolute requirement for ATP and CoA. MgCl2 enhances this activity 10-fold. The optimum pH is 8.5, and the apparent Km values for the radiolabeled substrate, ATP, CoA, and MgCl2 are 36, 154, 8, and 182 microM, respectively. The apparent Vmax is 32.4 nmol/min/mg protein for arachidonic acid. The presence of Triton X-100 (0.1%) in the assay medium caused a significant reduction in apparent Km (9.4 microM) and Vmax (25.7 nmol/min/mg protein) values. The enzymatic activity is thermolabile with a T1/2 of less than 1 min at 45 degrees C and a maximal activity at 40 degrees C. The breaking point or transition temperature is 25 degrees C in an Arrhenius plot. The activation energies were 95 kJ/mol from 0 to 25 degrees C and 30 kJ/mol from 25 to 40 degrees C. Fatty acid competition studies showed inhibition by unlabeled docosahexaenoic and arachidonic acids with a Ki of 31 and 37 microM, respectively, in the absence and 18 and 7.7 microM in the presence of Triton X-100. Palmitic acid and oleic acid slightly inhibited the reaction whereas linoleic acid inhibited it to a moderate extent. It is concluded that this very active enzyme can activate arachidonic acid as well as docosahexaenoic acid in brain microsomes. In addition, this reaction may be involved in regulating the pool size of these free fatty acids in brain by rapid removal through activation, thus limiting eicosanoid formation. Moreover, the rapid formation of polyenoic acyl-coenzyme A may participate in the retention of essential fatty acids in the central nervous system.
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PMID:Kinetic properties of arachidonoyl-coenzyme A synthetase in rat brain microsomes. 663 46

The effect of 35 minutes of warm ischemia (37C) on renal function and adenine nucleotide content of canine kidneys preserved for 24 and 48 hours in Euro-Collins (EC) solution was investigated. In addition, the effect of donor pretreatment with intravenous mannitol, furosemide and methylprednisolone and the addition of adenosine triphosphate (ATP/MgCl2) to the EC flush and storage solution was studied. Donor pretreatment or the addition of ATP/MgCl2 to the flushing and storage solution did not significantly affect postautotransplant renal function of kidneys stored for 24 hours, although it improved tissue adenine nucleotide levels. Results after 48-hour preservation were significantly poorer. These experiments demonstrate that canine kidneys subjected to 35 minutes of warm ischemia time can be stored for 24 hours in EC solution and thereafter provide immediate life-sustaining function.
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PMID:Successful 24-hour preservation of the ischemic canine kidney with Euro-Collins solution. 675 92

The metabolic consequences of low-temperature kidney preservation by pulsatile perfusion and cold storage were evaluated in canine kidneys by serial adenosine triphosphate (ATP) determinations. Serial cortical ATP levels were determined (1) after optimal harvest, (2) after 60 minutes of warm ischemia, and (3) after 60 minutes of warm ischemia followed by an intra-aortic infusion of ATP-MgCl2. After 24 hours of preservation, cortical ATP levels were significantly greater when pulsatile perfusion was used-both after optimal harvest and after 60 minutes of warm ischemia. Cortical ATP levels were significantly greater at 24 hours in both perfused and cold-storage kidneys when an intra-aortic infusion of ATP-MgCl2 was used following ischemia. These results may explain the 24-hour limitation of cold storage as well as its inferior results following ischemia injury. Furthermore, since ATP is critical in cellular metabolism, the technique of intra-aortic ATP-MgCl2 infusion warrants further investigation in the field of organ preservation.
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PMID:Renal cortical levels of adenosine triphosphate: restoration after prolonged ischemia by in situ perfusion of ATP-MgCl2. 700 46

The effect of ATP-MgCl2 treatment was investigated on the biochemical changes of preserved kidneys and on the functional recovery of hypoxically damaged and autotransplanted canine kidneys. We observed that ATP-MgCl2 administered before or during simple hypothermic storage did not protect the integrity of preserved kidney cells, as measured by enzyme wash-out (LDH and NAG) or by lactate release. If the compound was administered after 120 min or 180 min clamping of the renal artery, the solitary kidney showed a faster regeneration as measured by changes in serum creatinine level. The survival rates were significantly higher in the treated groups. Without warm ischemia of the kidney all of the autotransplanted dogs survived after surgery. After 60 min of warm ischemia the mortality rate was 100%, and the mean survival time in average 5 days. If ATP-MgCl2 was administered after the 60 min of warm ischemia, an improved recovery of the graft function was observed
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PMID:Effect of ATP-MgCl2 treatment on kidney preservation and on recovery of graft function. 701 Apr 79

Previous studies have shown that adenosine triphosphate-magnesium chloride (ATP-MgCl2) administered after 30 to 60 min of renal ischemia ameliorated the resulting acute renal failure in different species of animals. The purpose of this study was to determine whether addition of ATP-MgCl2 to the perfusate during renal preservation, prior to transplantation, might improve renal function. Dog kidneys were subjected to normothermic ischemia for 35 min, after which they were preserved by pulsatile perfusion for 24 hr at 7 C. The perfusate contained albumin in a balanced electrolyte solution with an without ATP-MgCl2. Following 24 hr of pulsatile perfusion, the kidneys were autotransplanted and renal function was determined 3 days post-transplantation. The results indicated that dog kidneys subjected to ischemia followed by perfusion preservation developed severe oliguric renal failure 3 days after transplantation. However, if ATP-MgCl2 was added to the perfusate, such kidneys demonstrated markedly improved renal function and ATP levels. These results indicate that kidneys which have been subjected to episodes of warm ischemia could be salvaged by addition of ATP-MgCl2 to the perfusate.
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PMID:Improved renal function using adenosine triphosphate-magnesium chloride in preservation of canine kidneys subjected to warm ischemia. 701 14

Progressive cell injury occurs with shock and ischemia, beginning with functional changes in the cell and cell membrane. Membrane transport and potential decrease, Na+ enters and K+ leaves cells; N+-K+ adenosine triphosphatase is activated, adenosine triphosphate (ATP) is used, and mitochondria are stimulated as increased lactate produces acidosis. Energy and cyclic adenosine monophosphate levels decrease, Ca2+ regulation is compromised, and nuclear function and protein synthesis are depressed. The cell swells, and further membrane changes occur with altered hormonal effects and mitochondrial uncoupling. Finally, lysosomes leak, intracellular and mitochondria disruption occurs, and the cell is destroyed. Based on these changes, attempts were made to directly support cell function during low-flow states. After volume replacement and vasoactive agents, other modalities, eg, substrates, membrane-stabilizing solutions, osmotic agents, and energy compounds were used. The use of ATP-MgCl2 was helpful in many experimental low-flow states, with an improvement in cell function mediated by micro-circulatory, cell membrane, or energy-recycling effects. Clinical examples of altered cell and organ function with ischemia and shock are numerous and play a critical role in the development of multiple systems failure. The potential for biochemical support and correction of these problems is now recognized. Benefits have already been achieved in myocardial preservation during cardiac operations, kidney preservation for transplantation, and circulatory and metabolic support of the injured and septic patient.
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PMID:Alterations in cell function with ischemia and shock and their correction. 702

It is well known that reticuloendothelial system (RES) function is depressed following thermal injury. Since previous studies have shown that adenosine triphosphate (ATP)-MgCl2 restored the depressed RES function following hepatic ischemia, the present study was undertaken to determine whether administration of ATP-MgCl2 following thermal injury would have any beneficial effects on the RES function. Thermal injury in rats was produced by immersing 30% of the skin surface area in 95 degrees C H2O for 12 sec. Immediately following this, the rats received saline s.c. and 0.25 ml of ATP-MgCl2 (12.5 mumol each) or an equivalent volume of saline i.p. RES function was evaluated by measuring the intravascular clearance of 131I-triolein-labeled gelatinized test lipid emulsion. The intravascular half-time (t/2) in the burned saline-treated rats was double that of control rats at 1 and 3 days post-burn, suggesting that significant depression in RES function occurred following thermal injury. At 5 days post-burn, although the t/2 was lower than at 3 days post-burn, it was still significantly higher than controls. Administration of ATP-MgCl2 following burn injury resulted in a t/2 and phagocytic index values similar to controls, indicating the impairment of phagocytic activity of the RES function following thermal injury was reversed with treatment.
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PMID:Impairment of reticuloendothelial function following thermal injury and its restoration with ATP-MgCl2 administration. 709 21

This study was designed to investigate the effects of ATP-MgCl2 when infused immediately 8 or 24 hr after 45 min of bilateral renal artery ischemia and to determine if an initial improvement in clearance of inulin (CIn) would be sustained throughout the course of recovery. In addition, the influence of ATP-MgCl2 on the pattern of recovery of whole kidney and single nephron function was assessed by determining the impact of this agent on proximal tubular pressure and transepithelial backleak. The postischemic administration of ATP-MgCl2 resulted in significantly enhanced recovery of CIn irrespective of the time of the infusion after the initial insult. This beneficial effect was sustained in that the ATP-MgCl2-treated rats had significantly better CIn 1, 3 and 7 days after the injury when compared to normal saline-treated animals. Moreover, single nephron inulin clearance (SNCIn) was better preserved than whole kidney CIn in both groups of animals and in the ATP-MgCl2-treated animals SNCIn was similar to control values even 1 day after the injury. The enhanced recovery of single nephron function in the ATP-MgCl2-treated animals resulted from reduced proximal tubular pressure and diminished backleak of tubular fluid. Animals given ATP-MgCl2 had better preservation of cellular morphology. Horseradish peroxidase was excluded from most epithelial cells and the interstitium in a manner similar to that seen in control animals while saline-treated rats demonstrated backleak of this tracer compound. Based on these studies, it appears that the beneficial effect of ATP-MgCl2 occurs because of the preservation of sublethally injured cells by augmentation of the process of recovery.
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PMID:Accelerated recovery of single nephron function by the postischemic infusion of ATP-MgCl2. 712 Jul 52

The purpose of this study was to determine whether hepatocellular function is altered following hepatic ischemia and whether ATP-MgCl2 has any effect on it. To study this, total hepatic ischemia in rats was produced for 60 minutes by placing a ligature around the hepatic artery, portal vein, and the common bile duct. At the end of the ischemic period, the ligature was removed, reestablishing blood flow to the liver. The animals then received IV either 0.25 ml saline (nontreated) or 0.25 ml ATP-MgCl2 (12.5 mumoles each) (treated). Three hours following the end of ischemia, indocyanine green (ICG) clearance was determined by infusing ICG at a concentration of either 5 mg/kg body wt (low) or 25 mg/kg body wt (high). Following infusion of ICG blood samples were taken at five, six, eight, ten, 12, 15, 18, and 20 minutes thereafter to determine the ICG concentration. The clearance of ICG at low as well as at high ICG concentration was markedly depressed in the nontreated animals, suggesting that significant depression in hepatic blood flow as well as hepatocellular function was evident even three hours after ischemia. Administration of ATP-MgCl2 following hepatic ischemia, however, resulted in ICG clearance values similar to sham-operated animals when ICG was given at low as well as high concentration. Thus, ATP-MgCl2 treatment following hepatic ischemia not only seemed to restore hepatic blood flow but also active membrane transport toward normal.
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PMID:Restoration of hepatocellular function and blood flow following hepatic ischemia with ATP-MgCl2. 713 43

Hepatic cell membrane potential (HCMP) and protein synthesis were studied in rats during and after a period (60 min) of liver ischemia. ATP-MgCl2 (5 mumol . 100 g bw-1) or saline was administered slowly intravenously before or after the period of liver ischemia. No beneficial effect of ATP-MgCl2 on the impaired HCMP or protein synthesis was observed. On the contrary, the post-ischemic restitution of these cellular metabolic variables was slower in animals receiving ATP-MgCl2 after the period of liver ischemia as compared with saline-treated rats. At the end of the ischemic period, ATP, glucose and lactate in liver tissue were the same in animals receiving ATP-MgCl2 or saline before ischemia. These results suggest that the beneficial effects previously reported after administration of ATP-MgCl2 in conditions with reduced hepatic blood flow are not primarily due to an improved metabolic situation in the liver.
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PMID:No beneficial effect of ATP-MgCl2 on impaired transmembrane potential and protein synthesis in liver ischemia. 716 90


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