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

Renal ischemia and reperfusion during aortic and renal transplant surgery result in ischemic-reperfusion injury. Ischemic preconditioning and adenosine infusion before ischemia protect against ischemic-reperfusion injury in cardiac and skeletal muscle, but these protective phenomena have not been demonstrated in the kidney. Rats were randomized to sham operation, 45-min renal ischemia, ischemic preconditioning with four cycles of 8-min renal ischemia and 5-min reperfusion followed by 45-min renal ischemia, systemic adenosine pretreatment before 45-min renal ischemia, or pretreatments with selective adenosine receptor subtype agonists or antagonists before 45-min renal ischemia. Forty-five minutes of renal ischemia followed by 24 h of reperfusion resulted in marked rises in blood urea nitrogen and creatinine. Ischemic preconditioning and adenosine pretreatment protected renal function and improved renal morphology. A(1) adenosine receptor activation mimics and A(1) adenosine antagonism blocks adenosine-induced protection. In addition, A(3) adenosine receptor activation before renal ischemia worsens renal ischemic-reperfusion injury, and A(3) adenosine receptor antagonism protects renal function. We demonstrate for the first time that rat kidneys can be preconditioned to attenuate ischemic-reperfusion injury and adenosine infusion before ischemic insult protects renal function via A(1) adenosine receptor activation. Our data suggest that an A(1) adenosine agonist and A(3) adenosine antagonist may have clinically beneficial implications where renal ischemia is unavoidable.
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PMID:Protective effects of renal ischemic preconditioning and adenosine pretreatment: role of A(1) and A(3) receptors. 1071 May 42

The activation of poly (ADP-ribose) synthetase (PARS) subsequent to DNA damage caused by reactive oxygen or nitrogen species has been implicated in several pathophysiological conditions, including ischemia-reperfusion injury and shock. The aim of this study was to investigate whether PARS inhibitors could provide protection against renal ischemia-reperfusion injury in the rat in vivo. Male Wistar rats were subjected to 45 min bilateral clamping of the renal pedicles, followed by 6 h reperfusion (control animals). Animals were administered the PARS inhibitors 3-aminobenzamide, 1, 5-dihydroxyisoquinoline, or nicotinamide during the reperfusion period. Ischemia, followed by reperfusion, produced significant increases in plasma concentrations of urea, creatinine, and fractional excretion of Na(+) (FE(Na)) and produced a significant reduction in glomerular filtration rate (GFR). However, administration of the PARS inhibitors significantly reduced urea and creatinine concentrations, suggesting improved renal function. The PARS inhibitors also significantly increased GFR and reduced FE(Na), suggesting the recovery of both glomerular and tubular function, respectively, with a more pronounced recovery of tubular function. In kidneys from control animals, histological examination revealed severe renal damage and immunohistochemical localization demonstrated PARS activation in the proximal tubule. Both renal damage and PARS activation were attenuated by administration of PARS inhibitors during reperfusion. Therefore, we propose that PARS activation contributes to renal reperfusion injury and that PARS inhibitors may be beneficial in renal disorders associated with oxidative stress-mediated injury.
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PMID:Inhibitors of poly (ADP-ribose) synthetase reduce renal ischemia-reperfusion injury in the anesthetized rat in vivo. 1074 21

The positive effect of insulin-like growth factor I (IGF-I) on the outcome of experimental acute renal failure has gained much attention in recent years. However, the potential positive effects of GH have been less intensively studied. Therefore, a study was designed in which rats suffering from post-ischemic renal failure were treated with high dosage growth hormone (GH). Forty-six rats were subjected to bilateral renal ischemia for 45 min. Following reperfusion the animals were treated with either human recombinant GH in a dosage of 2 mg/day given as subcutaneous injection or placebo. The animals were monitored daily for body weight, s-creatinine, s-urea and B-glucose. S-IGF levels were determined at the start of the experiment and at days 3 and 7. IGF-I and GH receptor mRNA were measured in the kidney and the liver of the surviving animals at the end of the experiment. Survival in the GH-treated rats was 42.9% as compared to 32.0% in the control group (not significant). Both groups of animals lost body weight in the initial phase. The loss in body weight was less pronounced for the GH-treated animals and the difference was significant at day 2 (P<0.05). The s-creatinine levels tended to be lower in the GH-group at all times studied, but the difference was not significant. The s-urea levels were significantly reduced by GH-treatment at day 2 (P<0.05). GH treatment caused no adverse effects on carbohydrate metabolism as studied by daily B-glucose determinations. The serum IGF-I levels were identical in both the groups at day zero. At day 3 the serum IGF-I levels had increased by approximately 30% in both groups. At day 7 the serum IGF-I level was 1600 ng/ml in the GH-treated group as compared to 1400 ng/ml in the placebo group (not significant). When placebo-treated uremic rats were compared to normal sham-operated animals GH-rec mRNA was down-regulated in the kidney and liver, while IGF-I mRNA was down-regulated only in the liver (P<0.05). GH treatment partly restored the GH-rec and IGF-I mRNA levels in both organs. The data are compatible with a severe GH resistance syndrome in acute renal failure.
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PMID:High dosage growth hormone treatment and post-ischemic acute renal failure in the rat. 1098 82

Ischemic acute renal failure is associated with vascular endothelial dysfunction. We examined whether vasodilatory antihypertensive agents would improve endothelial function in rats with ischemia/reperfusion renal injury. Rat kidneys were isolated and perfused after clipping of the bilateral renal arteries for 45 min and reperfusion for 24 h, and renal perfusion pressure and nitric oxide concentration in the venous effluent (chemiluminescence assay) were monitored. Preischemic administration of celiprolol (a beta-blocker; 100 mg/kg p.o.), benidipine (a calcium channel blocker; 1 mg/kg p.o.), or imidapril (an angiotensin converting-enzyme inhibitor; 3 mg/kg p.o.) restored endothelial function in rats subjected to acute renal ischemia (deltarenal perfusion pressure [10(-8) M acetylcholine]: sham -42+/-3%, ischemia -31+/-1%, ischemia +celiprolol -39+/-1%*, ischemia+benidipine -38+/-2%*, ischemia+imidapril -42+/-2%*; *p<0.05 vs. ischemia). Serum urea nitrogen and creatinine levels were also lower in the treated groups. Furthermore, ischemia-induced decreases in the response to acetylcholine and renal excretory function were smaller in SHR than in deoxycorticosterone-salt hypertensive rats, in which endothelial damage was marked. These results suggest that preischemic endothelial function may influence the degree of ischemic renal injury. Calcium channel blockers, converting-enzyme inhibitors, and endothelial NO synthase-activating beta-blockers had beneficial effects on renovascular endothelial dysfunction due to ischemia.
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PMID:Effects of vasodilatory antihypertensive agents on endothelial dysfunction in rats with ischemic acute renal failure. 1101 9

Although the search for effective methods of renal prophylaxis during aortic surgery spans many decades, definitive answers are scarce. The literature is voluminous, yet the amount of work clearly relevant to the specific clinical situation of perioperative prophylaxis is small. Given the significant morbidity and subsequent mortality involved with perioperative ARF, it is difficult to sit back and do nothing when pharmacologic agents empirically are believed to possibly benefit the patient. Care must be taken to apply data from different clinical scenarios in the literature to the situation at hand. Drugs felt to be innocuous, even in low doses, may be insidiously counterproductive or damaging if they are not managed properly. Maintaining an adequate preload and stable hemodynamics seems to be the most logical universal approach at this time. Furosemide treatment without maintaining an adequate volume status once diuresis commences may be detrimental, which is true with the diuretic effects induced by mannitol or dopamine. The tachycardia resulting from a relative hypovolemia and from the beta effects of dopamine can cause myocardial ischemia from increased oxygen demand. Low urine output does not portend a negative outcome in the face of an adequate intravascular volume any more than an induced diuresis prevents renal injury. Currently, minimization of renal ischemia and maintenance of an adequate intravascular volume and renal hemodynamics are the keys to optimizing renal outcome during aortic surgery. Other maneuvers are not definitive and should be cautiously undertaken.
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PMID:Intraoperative management of renal function in the surgical patient at risk. Focus on aortic surgery. 1109 87

The complex pathogenesis of ischemia reperfusion injury (IRI) includes endothelial expression of adhesion molecules, leukocyte recruitment and activation, reactive oxygen species production, and apoptotic and necrotic cell death. A role for complement in IRI of different organs, including kidney, has been proposed on the basis of results of experiments that used pharmacologic inhibitors as well as animals that were deficient in individual complement proteins. Here, renal IRI in mice was examined. Animals that were deficient in C3 had partial protection from IRI induced by 27.5 min of bilateral renal ischemia, followed by 20 h of reperfusion (blood urea nitrogen [BUN] values, 46.6 +/- 6.9 and 68.4 +/- 7.9 mg/dl in C3 -/- and C3 +/+ mice; n = 7 and 8, respectively; P = 0.033). Given the reduction in IRI in C3 -/- mice, it was investigated, by use of the rodent C3 convertase inhibitor CR1-related gene/protein y-Ig (Crry-Ig), whether exogenous administration of a complement inhibitor could lessen renal injury. Despite the use of Crry-Ig in high doses, there was no significant reduction of injury induced by 20 to 30 min of ischemia followed by up to 30 h of reperfusion. Histologic examination revealed acute tubular necrosis and neutrophilic infiltration, both of which correlated significantly with BUN values (P < 0.001). Of interest, C3 deposition around renal tubules was significantly less in animals with IRI, compared with that in unmanipulated controls (P < 0.001). In Crry-Ig-treated animals, C3 deposition was inversely proportional to BUN values (r = -0.63; P < 0.001), which presumably indicates that severe vascular IRI allowed access of the 160 kD Crry-Ig to the interstitium. Thus, renal IRI in mice may have a partial complement dependence, yet pharmacologic inhibition of the complement system does not seem to be effective, likely because of the presence of other mediator systems that operate in parallel.
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PMID:Inhibiting the complement system does not reduce injury in renal ischemia reperfusion. 1142 67

This study was conducted to investigate the involvement of the activin-follistatin system in renal regeneration after ischemic injury. Expression of mRNA for the activin beta(A) subunit was not detected in normal kidneys but increased markedly after renal ischemia. Immunoreactive beta(A) subunit was detected in tubular cells of the outer medulla in ischemic but not normal kidneys. Expression of mRNA for follistatin, an antagonist of activin A, was abundant in tubular cells of the outer medulla in normal kidneys and decreased significantly after renal ischemia. For assessment of the role of the activin-follistatin system in renal regeneration after ischemic injury, recombinant follistatin was intravenously infused into rats with renal ischemia, at the time of reperfusion. Exogenous follistatin prevented the histologic changes induced by ischemic injury, reduced apoptosis in tubular cells, and accelerated tubular cell proliferation. Serum levels of creatinine and blood urea nitrogen were significantly lower in follistatin-treated rats. Conversely, intravenous administration of recombinant activin A inhibited tubular cell proliferation after ischemic injury. These results indicate that the activin-follistatin system participates in renal regeneration after ischemic injury. Follistatin administered intravenously accelerates renal regeneration after renal ischemia, presumably by blocking the actions of endogenous activin.
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PMID:Involvement of the activin-follistatin system in tubular regeneration after renal ischemia in rats. 1146 41

Previous evidence suggests that both oxygen radicals and nitric oxide (NO) are important mediators of injury during renal ischemia-reperfusion (I-R) injury. However, the generation of reactive nitrogen species (RNS) has not been evaluated in this model at early time points. The purpose of these studies was to examine the development of oxidant stress and the formation of RNS during I-R injury. Male Sprague-Dawley rats were anesthetized and subjected to 40 min of bilateral renal ischemia followed by 0, 3, or 6 h of reperfusion. Control animals received a sham operation. Plasma urea nitrogen and creatinine levels were monitored as markers of renal injury. Glutathione (GSH) oxidation and 4-hydroxynonenal (4-HNE)-protein adducts were used as markers of oxidant stress. 3-Nitrotyrosine (3-NT) was used as a biomarker of RNS formation. Significant increases in plasma creatinine concentrations and urea nitrogen levels were found following both 3 and 6 h of reperfusion. Increases in GSH oxidation, 4-HNE-protein adduct levels, and 3-NT levels were observed following 40 min of ischemia with no reperfusion. Since these results suggested RNS generation during the 40 min of ischemia, a time course of RNS generation following 0, 5, 10, 20, and 40 min of ischemia was evaluated. Significant increases in 3-NT generation was detected as early as 10 min of ischemia and rose to values nearly 10-fold higher than Control at 40 min of ischemia. No additional increase was observed following reperfusion. The data clearly demonstrate that oxidative stress and RNS generation occur in the kidney during ischemia.
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PMID:Oxidative stress and reactive nitrogen species generation during renal ischemia. 1150 54

Ischemia-reperfusion injury (IRI) is a complex and incompletely understood process involving a cascade of events that culminates in apoptotic and/or necrotic cell death. Natural IgM antibodies and complement have been implicated in the pathogenesis of IRI in a variety of organ systems as have T lymphocytes in renal IRI. To investigate the role of Ig and T lymphocytes in renal IRI, recombination-activating gene (RAG)-1-deficient mice were studied. RAG-1(-/-) mice were not protected from acute renal failure induced by 27.5 min of bilateral renal ischemia and subsequent reperfusion [serum urea nitrogen levels 30 h after reperfusion, 155.2 +/- 5.6 and 152.8 +/- 11.4 mg/dl in RAG-1(-/-) and wild-type mice, respectively; n = 13 each]. Histological examination showed acute tubular necrosis and neutrophilic infiltration with no significant differences between groups. In contrast with other organ systems, Igs were not found in kidneys at time points ranging from 1 min to 30 h after ischemia. Thus Igs and mature T lymphocytes do not appear to play a significant role in the pathogenesis of IRI in the kidney.
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PMID:Injury in renal ischemia-reperfusion is independent from immunoglobulins and T lymphocytes. 1178 50

Blockade of NO production is followed by an increase in leukocyte rolling and adhesion resulting in some deleterious effects of ischemia. Preischemic administration of NO protects vascular integrity after reperfusion. Exogenous NO causes a direct reduction in leukocyte adhesion. This work was performed to test the hypothesis that exogenous NO administered during the preischemic period to the kidney alone, without coming into contact with the leukocytes, could also reduce leukocyte-endothelium adhesion. Adult rats were subjected to in situ isolation of the left kidney. Solutions were infused through the renal artery and drained through an incision in the renal vein, thus avoiding the systemic circulation. Group IC rats served as an ischemic control, and received 0.9% saline. Group NP received Na nitroprusside. Group S was a nonischemic control. Groups IC and NP were subjected to 75 min of renal ischemia. After this period, vascular structures were repaired and reperfusion allowed. A right nephrectomy was performed. Serum urea and creatinine, myeloperoxidase activity, and histopathological studies were carried out at different intervals after reperfusion. Survival at 15 days was 46%, 80%, and 100% in groups IC, NP, and S, respectively. Differences between groups for serum urea and creatinine were significant only during the first seven days. Myeloperoxidase values were significantly higher in group IC. All rats from group IC and only 20% from group NP showed histological evidence of necrosis. Thus, exogenous NO is protective and acts selectively upon the kidney, modulating its interactions with polymorphonuclear cells after ischemia/reperfusion.
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PMID:Exogenous nitric oxide protects kidney from ischemia/reperfusion. 1190 99


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