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Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondrial Ca2+ accumulation and mitochondrial respiratory dysfunction have been observed after renal ischemia. The present study examined the effects of ischemia and reperfusion on cellular energy production and mitochondrial Ca2+ transport after 50 min of bilateral renal artery and vein clamping in the anesthetized rat. Prior to reflow, tissue ATP and total adenine nucleotide levels were severely reduced. These nucleotide levels recovered towards normal but remained lower than control values throughout 24 h of reperfusion. Energy-linked mitochondrial Ca2+ uptake was unmeasurable, mitochondrial Ca2+ efflux was increased and the mitochondria were unable to maintain a steady-state free Ca2+ concentration prior to reflow. Three hours of reperfusion was associated with a normalization of mitochondrial Ca2+ uptake, release, and steady-state buffering. However, progressive deterioration subsequently occurred in these processes. Thus the mitochondrial Ca2+ accumulation previously observed during the later stages of postischemic reperfusion (3-24 h) is due neither to an increase in the rate of active Ca2+ uptake nor to a decrease in the rate of Ca2+ release. The present results therefore suggest that passive mitochondrial Ca2+ accumulation may occur during the later stages of reperfusion, probably due to a progressive increase in the cytosolic Ca2+ concentration.
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PMID:Adenine nucleotide metabolism and mitochondrial Ca2+ transport following renal ischemia. 394 11

In the present study 1 h of total occlusion of the left renal artery in conscious rats was chosen as experimental model of ischemic acute renal failure (ARF), while the contralateral kidney was left intact. Chronic high dietary sodium intake, acute isotonic saline infusion, or administration of saralasin did not protect from ARF. Furosemide, mannitol, and verapamil converted oliguric into non-oliguric ARF in 100%, 75%, and 60% of the animals, resp. Protection from oliguria and preservation of GFR inversely correlated with the depression of cortical ATP-concentration (control: 1.32 +/- 0.07 mumoles/g wet weight) 6 h after ischemia by 16%, 41%, and 58% in mannitol- and verapamil- treated rats and in untreated rats, resp. At this time, Na-K-ATPase enzyme activities in renal cortex and papilla were unaffected, while enzyme activity in outer medulla was suppressed from 15.4 +/- 1.4 to 9.4 +/- 1.0 mumoles Pi/mg protein h in all groups of animals. The results suggest that in this model of ARF renal ischemia not only affects cellular energy supply in renal cortex but also causes severe structural and functional impairment in the outer medulla, probably leading to tubular obstruction and depression of glomerular function. Pharmacological protection from ischemic oliguric ARF cannot be achieved by prior induction of high urine flow rates alone but depends on the degree of metabolic and functional reserve of the injured tubular epithelium.
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PMID:Renal functional and metabolic studies on the role of preventive measures in experimental acute ischemic renal failure. 641

During renal ischemia, ATP is degraded to hypoxanthine. When xanthine oxidase converts hypoxanthine to xanthine in the presence of molecular oxygen, superoxide radical (O-2) is generated. We studied the role of O-2 and its reduction product OH X in mediating renal injury after ischemia. Male Sprague-Dawley rats underwent right nephrectomy followed by 60 min of occlusion of the left renal artery. The O-2 scavenger superoxide dismutase (SOD) was given 8 min before clamping and before release of the renal artery clamp. Control rats received 5% dextrose instead. Plasma creatinine was lower in SOD treated rats: 1.5, 1.0, and 0.8 mg/dl vs. 2.5, 2.5, and 2.1 mg/dl at 24, 48, and 72 h postischemia. 24 h after ischemia inulin clearance was higher in SOD treated rats than in controls (399 vs. 185 microliter/min). Renal blood flow, measured after ischemia plus 15 min of reflow, was also greater in SOD treated than in control rats. Furthermore, tubular injury, judged histologically in perfusion fixed specimens, was less in SOD treated rats. Rats given SOD inactivated by prior incubation with diethyldithiocarbamate had plasma creatinine values no different from those of control rats. The OH X scavenger dimethylthiourea (DMTU) was given before renal artery occlusion. DMTU treated rats had lower plasma creatinine than did controls: 1.7, 1.7, and 1.3 mg/dl vs. 3.2, 2.2, and 2.4 mg/dl at 24, 48, and 72 h postischemia. Neither SOD nor DMTU caused an increase in renal blood flow, urine flow rate, or solute excretion in normal rats. The xanthine oxidase inhibitor allopurinol was given before ischemia to prevent the generation of oxygen free radicals. Plasma creatinine was lower in allopurinol treated rats: 2.7, 2.2, and 1.4 mg/dl vs. 3.6, 3.5, and 2.3 mg/dl at 24, 48, and 72 h postischemia. Catalase treatment did not protect against renal ischemia, perhaps because its large size limits glomerular filtration and access to the tubular lumen. Superoxide-mediated lipid peroxidation was studied after renal ischemia. 60 min of ischemia did not increase the renal content of the lipid peroxide malondialdehyde, whereas ischemia plus 15 min reflow resulted in a large increase in kidney lipid peroxides. Treatment with SOD before renal ischemia prevented the reflow-induced increase in lipid peroxidation in renal cortical mitochondria but not in crude cortical homogenates. In summary, the oxygen free radical scavengers SOD and DMTU, and allopurinol, which inhibits free radical generation, protected renal function after ischemia. Reperfusion after ischemia resulted in lipid peroxidation; SOD decreased lipid peroxidation in cortical mitochondria after renal ischemia and reflow. We concluded that restoration of oxygen supply to ischemic kidney results in the production of oxygen free radicals, which causes renal injury by lipid peroxidation.
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PMID:Oxygen free radicals in ischemic acute renal failure in the rat. 643 91

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

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

Acute renal failure in dogs occurs following 40 min of total renal ischemia induced by a 40-min infusion of norepinephrine (NE; 0.75 micrograms/kg/min) into the renal artery. Similar functional impairment is seen following 50 min of bilateral renal pedicle clamping in the rat. Attending these renal ischemic insults a progressive increase in mitochondrial (Mito) calcium (Ca++) accumulation occurs during reflow. Although Mito respiration and Mito Ca++ kinetics (uptake and release) are abnormal during ischemia, prior to reflow, as are tissue ATP levels, reflow in the first 1-3 h after ischemia is associated with recovery of these measurements to almost normal levels. Between 3 and 24 h of further reflow, however, Mito functional deterioration is again observed. Verapamil (5 micrograms/kg/min) infused intrarenally for 2 h after NE or for 30 min prior to NE protected kidneys from the low glomerular filtration rate which follows renal ischemia in untreated dogs. Since mannitol and polyethylene glycol, two solutes with relatively high reflection coefficients, also exert protection in this model, it may be that Ca++ leak into the cytosol of ischemically damaged kidney cells eventually aborts the Mito recovery which accompanies reflow; these impermeant solutes (by preventing cell swelling) and the Ca++ blocker Verapamil may work by different mechanisms to prevent increased cytosolic Ca++ after renal ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ischemic acute renal failure--pathogenetic steps leading to acute tubular necrosis. 665 80

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

Postischemic thyroxin (T4) enhances restitution of cellular ATP and accelerates recovery of renal function. This effect is not related to global improvement in cell integrity. To determine the mechanism by which recovery of cellular ATP is enhanced, the effect of T4 on mitochondrial ATP production was evaluated using specific inhibitor stop assays for mitochondrial phosphate transport and ADP translocator activity. Rats were subjected to 45-min renal ischemia and given normal saline (NS, 0.5 ml) or T4 (20 micrograms/kg) during the reflow period. By 30-min reflow; the values for apparent endpoint of phosphate transport (PiTm, nmol Pi/mg mitochondrial protein) had recovered to rates seen in nonischemic animals (10.3 +/- 0.9) and remained stable at 120 min. T4 treatment did not affect PiTm. In contrast, the apparent endpoint of ADP transport (ADPTm, nmol ADP/mg mitochondrial protein) was dramatically decreased in NS rats at 30-min (6.7 +/- 0.5) and 120-min (13.7 +/- 1.0) reflow compared with nonischemic control rats (24.7 +/- 2.4). T4 significantly improved ADPTm by 30 min (10.1 +/- 0.6, P < 0.05). By 120 min T4 stimulated ADPTm (37.7 +/- 5.2, P < 0.05) to exceed nonischemic control values. These data suggest the following: 1) postischemic mitochondrial PiTm recovers to control values by 30 min of reflow; 2) T4 does not augment PiTm; 3) renal ischemia causes a dramatic decrease in mitochondrial ADPTm; 4) postischemic T4 significantly enhances mitochondrial nucleotide transport at 30-min reflow; 5) by 120-min reflow, T4 rats have ADPTm which exceeds control values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Postischemic thyroxin stimulates renal mitochondrial adenine nucleotide translocator activity. 773 9

The signal transduction pathways that mediate activation of trans acting factors controlling an organ's response to ischemia are unknown. The stress-activated protein kinases (SAPKs), a subfamily of the extracellular signal-regulated kinases (ERKs), phosphorylate c-Jun within the amino-terminal transactivation domain and are activated in response to a variety of cellular stresses. We determined whether SAPKs are activated in response to ischemia, an extreme, albeit common, pathophysiologic stress. Rats underwent 40 min of renal ischemia followed by reperfusion for 0, 5, 20, or 90 min. SAPKs were immunoprecipitated from kidney lysates and kinase activity assayed with recombinant GST-c-Jun(1-135), containing the amino-terminal transactivation domain of c-Jun as substrate. SAPKs were not activated by ischemia alone, but reperfusion for as little as 5 min was associated with a 4.6-fold increase in kinase activity. Kinase activity was increased 7.6-fold at 20 min following reperfusion and remained elevated at 90 min of reperfusion (4.9-fold). In contrast, activity of the related ERK-1 and -2 was increased only 1.3-fold and only at the 5-min reperfusion time point. When SAPKs were immunodepleted from kidney extracts prior to incubation of the extracts with agarose-coupled GST-c-Jun(1-135), it was found that SAPKs accounted for the majority of the amino-terminal c-Jun kinase activity of kidney at 5 min following reperfusion. In Madin-Darby canine kidney epithelial cells, ATP repletion, following ATP depletion induced by chemical anoxia, was associated with a 9-15-fold activation of SAPKs with a similar time course of activation to that seen in the kidney after ischemia and reperfusion. In conclusion, the SAPKs are markedly activated very early after reperfusion of ischemic kidney and following ATP repletion of anoxic cells in culture. We propose that this activation of SAPKs may trigger part of the kidney's early genetic response to ischemia, possibly by enhancing trans acting activity of c-Jun.
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PMID:The stress-activated protein kinases are major c-Jun amino-terminal kinases activated by ischemia and reperfusion. 792 79


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