Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0920646 (renal ischemia)
2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since previous studies have shown a protective effect of the administration of adenosine triphosphate-magnesium chloride (ATP-MgCl2) in shock, the present study was undertaken to determine the effect of the infusion of ATP-MgCl2 after 30 minutes of renal artery occlusion. In animals who received no infusion or only MgCl2, the combination of reduced glomerular filtration rate (GFR), marked diuresis, and reperfusion of the outer cortex suggested that these animals were in the early recovery phase of acute renal failure. In the animals who received ATP-MgCl2, there was improved GRF, no diuresis, and a normal pattern of cortical blood flow distribution. These findings would suggest that the infusion of ATP-MgCl2 appears to have either ameliorated the effect of renal ischemia, or to have accelerated the recovery process. While the precise mechanism of action of ATP-MgCl2 remains unknown, these observations may have important implications for future use in organ preservation and the management of acute renal failure.
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PMID:Postichemic renal failure: accelerated recovery with adenosine triphosphate-magnesium chloride infusion. 86 Sep 22

The role of nucleoside uptake in the enhanced metabolic recovery seen with postischemic ATP.MgCl2 was assessed by determining the effect of S-(p-nitrobenzyl)-6-thioinosine (NBTI) on postischemic ATP recovery in rats given normal saline (NS), ATP.MgCl2, or adenosine after 45 min of bilateral renal ischemia. In NS-infused animals, postischemic administration of NBTI (250 nmol) had no significant effect on the pattern of ATP recovery. In animals given 50 mumol ATP.MgCl2, coinfusion of NBTI significantly reduced the renal ATP content 2 h after reperfusion but blocked only one-half of the enhancement in renal ATP content compared with animals given ATP.MgCl2 alone. In animals postischemically infused with [2,5,8-3H]ATP.MgCl2 (50 mumol) there was significant labeling of nucleotides, nucleosides, and bases after 2 h of reperfusion. The specific activity of the adenosine pool was consistent with significant label uptake in the form of adenosine. Coinfusion of NBTI led to a significant reduction in label incorporation into renal ATP and total adenine nucleotide pools. These data are consistent with an important role for an NBTI-sensitive nucleoside uptake mechanism in the enhanced metabolic and functional recovery observed in ischemically injured kidney treated by postischemic infusion of ATP.MgCl2.
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PMID:Role of nucleoside uptake in renal postischemic ATP synthesis. 162 13

Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy was used to measure adenosine triphosphate (ATP) concentration and pH in vivo in rabbits subjected to a 40-minute period of unilateral renal ischemia to determine the effect of infusing ATP-magnesium chloride (MgCl2, 100 mumol/kg) versus saline at the initiation of reperfusion. Data were compared initially by analysis of variance and then analyzed further using a general linear model with covariate adjustment. ATP-MgCl2-treated animals did not have higher ATP levels during recovery but did have significantly higher renal blood flow (p less than 0.05), a significantly decreased rate of recovery from acidosis (p less than 0.05), and significantly higher urinary output (p less than 0.01) than saline-treated animals during the recovery period. Therefore, treatment with ATP-MgCl2 improves postischemic functional parameters in this model of moderate injury without functioning as a direct source of ATP or its precursors. These data add support to the emerging concept that intracellular acidosis protects cells from reperfusion injury.
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PMID:31P-NMR evaluation of postischemia renal ATP and pH levels after ATP-MgCl2 treatment in rabbits. 163 93

Postischemic administration of ATP-MgCl2 is known to enhance recovery of renal function and accelerate the restitution of cellular ATP levels. To differentiate between a direct and indirect effect of the exogenous nucleotide, rats were subjected to 45 min of bilateral renal ischemia and were infused with either ATP-MgCl2, AMP-MgCl2, or normal saline. The immediate recovery of the cellular ATP was similar in all three groups of animals, whereas the subsequent recovery was accelerated by the infusion of either nucleotide. Since ATP-MgCl2 and AMP-MgCl2 produced similar results, this study provides evidence that exogenous ATP may act by providing precursors for the resynthesis of the cellular adenine nucleotide pool rather than being a direct source of energy.
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PMID:Postischemic ATP-MgCl2 provides precursors for resynthesis of cellular ATP in rats. 348 99

The present study compared the effects of ATP-MgCl2 or ATP-Na2 administration on renal function and cellular metabolism following renal ischemia in rabbits. Following 100 min of ischemia, the blood flow to the kidney was allowed to reestablish itself, and the rabbits received either saline, ATP-MgCl2 (17.5 mumole/kg each), or ATP-Na2 (17.5 mumole/kg) intravenously. ATP-MgCl2 administration following ischemia significantly accelerated the recovery of renal function. However, administration of ATP-Na2 failed to show any beneficial effect on the recovery process. The changes in renal cellular ketone body ratio (acetoacetate/beta-hydroxybutyrate), energy charge, and pyruvate/lactate indicated that ATP-MgCl2, but not ATP-Na2, reversed ischemically induced impairment in renal cellular metabolism. Reduction in the renal blood flow caused by ischemia was also improved with ATP-MgCl2 treatment. These results indicate that ATP should be given in the form of ATP-MgCl2 for it to be effective following renal ischemia. The results also suggest that the salutary effect of ATP-MgCl2 following renal ischemia could occur through the improvement of cellular metabolism and concomitant improvement in tissue blood flow.
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PMID:Effects of ATP-MgCl2 and ATP-Na2 administration on renal function and cellular metabolism following renal ischemia. 383 26

We used high-resolution phosphate 31(31P)--nuclear magnetic resonance spectroscopy to study the effects of ischemia and reperfusion on intracellular adenosine triphosphate (ATP) and pH changes in isolated perfused rat kidneys. With renal ischemia, ATP levels fell rapidly and the inorganic phosphate (Pi) peak shifted, indicating acidosis. On reperfusion after 45 minutes of warm ischemia, there was a 56% rise in tissue ATP levels within ten minutes that then slowly declined; by 75 minutes the levels were only 33% of normal. Perfusate flow decreased from 21.2 +/- 0.9 mL/min (mean +/- SE) to 16.5 +/- 1.1 mL/min and the Pi peak did not shift during reperfusion. When 0.3mM ATP complexed to magnesium chloride (ATP-MgCl2) was added to the perfusate after ischemia, renal ATP levels increased to 69% of normal within ten minutes of reperfusion and by 75 minutes they were normal. Perfusate flow was also normal during reperfusion. The Pi peak shifted back to the normal frequency, indicating correction of the intracellular acidosis. Thus, intracellular acidosis, ATP depletion, and decreased flow during reperfusion injury were rapidly reversed and sustained by the postischemic administration of ATP-MgCl2.
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PMID:Adenosine triphosphate--magnesium chloride ameliorates reperfusion injury following ischemia as determined by phosphorus nuclear magnetic resonance. 387 13

The present study was undertaken to investigate the effect of ATP-MgCl2 on the recovery of renal function following renal ischemia. Bilateral renal ischemia was produced for 90 minutes in dogs. Immediately after the release of ischemia, ATP-MgCl2 (50 mumoles/kg) was given intravenously. Serum creatinine and FeNa were measured following the release of ischemia. Renal cellular energy charge, glomerular endothelial thickness and per cent circularity of interstitial cells were measured. Creatinine and FeNa were significantly lower in ATP-MgCl2 treated dogs compared to those in saline treated controls. Changes in energy charge, glomerular endothelial thickness and per cent circularity indicated ischemically induced renal cellular edema was reversed with ATP-MgCl2 through the improvement of energy metabolism. Taking those experimental data into consideration, ATP-MgCl2 was given to 16 acute renal failure patients and 13 patients survived. ATP-MgCl2 administration is effective for the treatment of acute renal failure.
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PMID:Experimental and clinical study on ATP-MgCl2 administration for postischemic acute renal failure. 660 31

To determine the mode of action of the beneficial effect of adenosine triphosphate (ATP)-MgCl2, recovery of microinjected inulin, proximal tubular pressure (PTP), and cellular damage as quantitated by histomorphometric analysis of necrosis and swelling were evaluated at 2, 6, and 24 hours after 45 minutes of renal ischemia in rats treated with either normal saline or ATP-MgCl2. At 2 hours both groups of rats demonstrated increased permeability to inulin, elevated PTP, and severe ischemic damage and necrosis. By 6 hours ATP-MgCl2 rats had less tubular back leak of inulin, PTP was modestly reduced, and ultrastructural studies demonstrated improved cellular morphologic features with evidence of early regenerative changes. The saline rats had progressive ischemic cellular damage. At 24 hours ATP-MgCl2 rats had reestablished tubular integrity, PtP had fallen, and ischemic alterations were improved, with only focal evidence of necrosis. Saline-treated rats still had a back leak of inulin, elevated PTP, and progressive ischemic injury. This study demonstrates that 1) cellular damage continues to occur for 6 hours after renal ischemia; 2) ATP-MgCl2 enhances recovery of tubular integrity and cellular morphologic features. The salutary effect of ATP-MgCl2 appears related to the preservation of sublethally injured cells and acceleration of the process of restoration and repair of damaged cells.
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PMID:Accelerated cellular recovery after an ischemic renal injury. 660 59

The postischemic infusion of ATP-MgCl2 will enhance the recovery of both glomerular and tubular function. To assess the effect of ATP-MgCl2 on tissue nucleotides, 31P nuclear magnetic resonance (31P-NMR) spectra were obtained continuously in vivo from the left kidney of rats that had been subjected to 45 min of renal ischemia and then infused with either normal saline or ATP-MgCl2. 31P-NMR spectra with distinct peaks for alpha-, beta-, and gamma-phosphate of ATP, sugar phosphate, and inorganic phosphate were collected every 7 min before, during, and after renal artery occlusion. During ischemia, the ATP beta-peak (the only peak unique to ATP) fell rapidly to 10% of control values in both groups of animals. By 120 min after the ischemic insult, the animals treated with ATP-MgCl2 had recovery of renal ATP to 89 +/- 2.6%, which is significantly greater (P less than 0.001) than 65.2 +/- 1.8% found in rats given normal saline. These data indicate that 1) 31P-NMR can be used to assess renal ATP levels continuously in vivo; 2) during renal ischemia ATP levels fall quickly to less than 10% of control values; 3) tissue ATP returns relatively slowly to control values in rats given normal saline, whereas postischemic treatment with ATP-MgCl2 results in an accelerated recovery of tissue ATP levels. These findings provide a biochemical correlate to the improvement in renal function previously described.
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PMID:Enhanced recovery of renal ATP with postischemic infusion of ATP-MgCl2 determined by 31P-NMR. 660 93

Models of post-ischemic acute renal failure were prepared in rats. The effects of adenosine triphosphate-magnesium chloride (ATP-MgCl2) administration following renal ischemia on possible changes in renal function and renal cellular metabolism following ischemia were studied using the model. The results obtained revealed the following: 1) Over 40 minute-renal ischemia led to significant lowerings of renal cellular ATP level and energy charge (EC) by as much as 45 to 57% and 4.1 to 7.4% of the control, respectively, at 90 min following re-establishment of renal blood flow. Significant increases in Na+ in renal tissues were observed, but no changes in K+. Further, lactate level in renal tissues tended to increase with prolonged ischemic time by as much as 27 to 31% of the control, with a renal cellular anaerobic metabolism observed. On the other hand, at 24 hr following recirculation of the kidney, plasma creatinine (P-Cr), blood urea nitrogen (BUN) and fraction excretion of sodium (FENa) increased significantly, and creatinine clearance (C-Cr) and urine osmotic pressure decreased significantly, as compared with the control, indicating ischemic acute renal failure. 2) Intravenous injection of ATP-MgCl2 at a dose of 25 mumole/kg and a rate of 1.0 mumol/min after 40 min of renal ischemia led to significant lowerings of P-Cr, BUN and FENa to 36, 35 and 35% of the control (injected with physiological saline solution), respectively, and to significant elevation of C-Cr and urine osmotic pressure by as much as 41 to 31% of the control respectively, at 24 hr after reperfusion. The above results suggested that the ischemic acute renal failure was caused by the decreases in renal cellular ATP and EC with ischemia, resulting in renal cellular metabolic disturbances. It was further suggested that ATP-MgCl2 administered for such a pathological condition could make significant improvements in renal function.
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PMID:[Effect of adenosine triphosphate-magnesium chloride administration for post-ischemic acute renal failure (I)]. 660 69


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