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

The pathophysiology of ischemia-reperfusion renal injury is mediated, in part, by the generation of the vasoconstricting prostanoid thromboxane A2 (TXA2). This study was undertaken to evaluate the renoprotective effects, as well as the optimal timing and dosage, of a selective thromboxane synthetase inhibitor, OKY-046, in a unilateral nephrectomized, 60 min ischemia, 72 hr reperfusion, rodent model. Forty-one rats were subjected to right nephrectomy only (group A), or right nephrectomy with 60 min of left renal ischemia and treatment with inactive vehicle only (group B), or 2 mg/kg or 4 mg/kg of OKY-046 administered intravenously before (groups C and D) or after (groups E and F) pedicle clamping. Outcome variables included animal survival; change in kidney weight; 0, 24, and 72 hr plasma creatinine (CR); urea nitrogen (BUN); thromboxane B2 (TXB2) and 6-keto prostaglandin F(1alpha) (6 kPGF(2alpha)) levels; creatinine clearance (CRCL); and histologic evidence of renal injury. Animal survival and postperfusion kidney weight were not significantly different among the groups. However, renal functional parameters were significantly improved with the 2 mg/kg dose of OKY-046 administered after renal ischemia. (group B 72 hr Cr= 8.01 +/- 1.1 mg% vs. group E=3.99 +/- 1.5 mg%, and group B 72 hr BUN=241.3 +/- 32.8 mg% vs. group E=52.6 +/- 22.5 mg%). The CRCL was also improved in group E vs. group B, although these results did not reach statistical significance (group B=0.069 ml/min vs. group E=0.194 ml/ min). The 24 hr TXB2 levels were significantly increased in group B (0 hr=754.1 +/- 219.4 pg/ml vs. 24 hr=2055.9 +/- 550.0 pg/ml), and pre- or posttreatment with OKY-046 abrogated this increase (group C 0 hr=517.1 +/- 80.9 pg/ml vs. 24 hr=384.7 +/- 251.5 pg/ml, and group E 0 hr=781.6 +/- 390.4 pg/ml vs. 24 hr=183.0 +/- 81.4 pg/ml). The 24 hr 6 kPGF(1alpha) levels decreased in all groups, whereas 72 hr 6 kPGF(1alpha) levels increased above baseline in groups A, C, and E, but not in group B. These data demonstrate the beneficial effects of thromboxane A2 synthesis inhibition in the setting of ischemia-reperfusion injury and suggest that this renoprotection correlates with late vasodilatory prostanoid synthesis.
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PMID:Evaluation of the thromboxane A2 synthetase inhibitor OKY-046 in a warm ischemia-reperfusion rat model. 863 64

Hypothermia and preservative perfusates have been used to decrease ischemic renal injury. This study was performed to identify the preservative function of perfusates independent of the effects of hypothermia. Rats underwent 45 minutes of renal ischemia. Rectal and renal parenchyma temperatures were monitored and maintained within 1 degree C of normal. Perfusates were University of Wisconsin solution (UW), Euro-Collins solution, normal saline solution, and Ringer's lactate solution. A nonperfused ischemic control and a nonischemic control group were also evaluated. Parameters evaluated included serum creatinine and blood urea nitrogen levels, renal ischemic injury grade, renal weight, and gross appearance of the injured kidney. Rats treated with UW solution were found to have a significantly lower creatinine, blood urea nitrogen, and injury grade than the other three perfused groups. The external gross appearance of the UW-treated kidneys was normal, whereas that of the other groups demonstrated moderate to severe injury. Although the mean right/left renal weight difference of the UW-treated group was lower than that of the other three groups, this was not statistically significant. Under normothermic conditions in rats, UW solution affords significant renal protection from ischemia. Euro-Collins, normal saline, and Ringer's lactate solutions display no significant protective effect.
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PMID:Normothermic renal artery perfusion: a comparison of perfusates. 873 63

We evaluated the feasibility of magnetic resonance imaging (MRI) for early detection of tubular injury by monitoring changes in the apparent diffusion coefficient (ADC) of renal water in a rat model of myohemoglobinuric glycerol-induced acute renal failure (ARF). Diffusion-weighted MRI was performed concurrently with measurements of serum creatinine and blood urea nitrogen (BUN), evaluation of renal perfusion with dynamic contrast-enhanced MRI, and renal morphological examination. ADC values in the cortex and outer medulla significantly declined within minutes after the glycerol administration (70-75% of control at 4 min and 50-60% of control at 15 min). Contrast-enhanced MRI demonstrated renal hypoperfusion at 20 min after the onset of injury. Light microscopy showed normal glomeruli and edematous tubular epithelial cells at 10 and 30 min, with more severe swelling and protein casts at 30 min. No changes in serum creatinine or BUN levels were detected. We hypothesize that decrease in renal ADC may be attributed to renal ischemia and to subsequent intracellular accumulation of diffusion-restricted water. Similar imaging evaluation in other experimental models of ARF, and in patients, will define the diagnostic value of renal ADC changes in early detection of acute tubular injury.
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PMID:Early detection of acute tubular injury with diffusion-weighted magnetic resonance imaging in a rat model of myohemoglobinuric acute renal failure. 882 May

Reperfusion after ischemia induces cytokines, chemoattractant chemokines, adhesion molecules, and nitric oxide (NO). The resultant neutrophil adherence and NO potentiates renal injury. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a potent anti-inflammatory agent that inhibits neutrophil migration and production of neutrophil chemokines and NO. Since neutrophils and NO promote renal ischemic injury, we sought to determine if alpha-MSH inhibits renal injury in a model of bilateral renal ischemia. alpha-MSH significantly reduced ischemia-induced renal damage, measured by changes in renal histology and plasma blood urea nitrogen and creatinine in mice. alpha-MSH significantly decreased tubule necrosis, neutrophil plugging, and capillary congestion. Delay of alpha-MSH treatment for 6 h after ischemia also significantly inhibited renal damage. alpha-MSH also significantly inhibited ischemic damage in rats. To begin to determine the mechanism of action of alpha-MSH, we measured its effects on mediators of neutrophil trafficking and induction of the inducible isoform of NO synthase-II. alpha-MSH inhibited ischemia-induced increases in mRNA for the murine neutrophil chemokine KC/IL-8. alpha-MSH also inhibited induction of mRNA for the adhesion molecule ICAM-1, which is known to be critical in renal ischemic injury. alpha-MSH inhibited nitration of kidney proteins and induction of NO synthase-II. We conclude: (a) alpha-MSH protects against renal ischemia/reperfusion injury; and (b) it may act, in part, by inhibiting the maladaptive activation of genes that cause neutrophil activation and adhesion, and induction of NO synthase.
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PMID:Alpha-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats. 907 23

The purpose of this study was to characterize the time course of renal ischemia-reperfusion injury in the rat. Male Sprague-Dawley rats were subjected to bilateral renal clamping for 45 min. At reestablishment of blood flow, the rats were divided into nine groups (representing 0, 0.5, 1, 2, 4, 6, 9, and 24 h, and 1 week post-ischemia). At each time point, blood samples were taken for analysis of blood urea nitrogen (BUN) and creatinine, and both kidneys were harvested for histopathology and myeloperoxidase activity (MPO) assays. An intracellular adhesion molecular (ICAM-1) monoclonal antibody (IMAb) was tested in a separate group of animals (1 mg/rat) to confirm that it may provide renal protection previously reported by Kelly et al. (1994). Following renal ischemia, significant increases in serum BUN and creatinine were observed compared to levels in normal animals. Serum BUN and creatinine increased 2, 4, and 6 h post-ischemia leading to peak elevations 24 h post-ischemia. Values returned to normal at the 1 week time point. MPO activity was slightly increased 2 and 4 h following ischemia, with peak elevations occurring at the 6-h and 9-h time points. Histopathologic examination of kidneys revealed that the most severe damage occurred at the 24-h time point, which correlated with the peak elevations in serum BUN and creatinine. Evidence of renal injury was still evident histologically 1 week following ischemia, although renal function tests (BUN and creatinine) had returned to normal. In summary, renal injury following ischemia may be demonstrated as early as 4 h post-ischemia as judged by changes in renal function, MPO levels, and renal histopathology. However, based upon renal function tests and histology, peak injury is observed approximately 24 h following ischemia. The ICAM-1 monoclonal antibody, ICAM-Ab, provided some renal protection against ischemia-reperfusion injury in this study as measured by serum creatinine, BUN and renal histopathology. However, in contrast to the results reported by Kelly et al., the magnitude of the protective effects was not as dramatic in the present study, and furthermore, no reductions in renal MPO activity were observed.
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PMID:Characterization of renal ischemia-reperfusion injury in rats. 908 82

Contrast-media associated nephropathy (CMAN) consists in a sudden impairment of glomerular filtration rate following exposure to radiographic contrast materials. Damage may be limited to an asymptomatic mild increase of blood creatinine, or reach the highest levels of nitrogen retention compatible with acute renal failure. Some preexisting clinical conditions or pathologies may lead to CMAN: not only renal insufficiency, diabetes mellitus, multiple myeloma, congestive heart failure and severe hypertension, but also simple dehydration and a growing series of immunologic diseases are recognized as predisposing condition. The exact mechanism responsible for renal injury is still doubtful but recently animal models have shown substantial ischemic changes that may be added to the traditional presumed pathogenesis of direct tubular toxicity and intra-tubular obstruction. As renal ischemia stimulates both endogenous vasoconstrictor and vasodilator substances, it is now supposed that CMAN acts similarly to non-steroidal anti-inflammatory agents, selectively inhibiting the vasodilatory prostaglandin phase and therefore causing a derangement of the physiologic vasoconstriction/vasodilatation balance of renal circulation. The role of oxygen free radicals to contribute to renal dysfunction is considered. Low osmolality non ionic contrast media when compared to conventional high osmolality ionic contrast media have reduced but not eliminated CMAN. Simple but effective lines of prevention include the previous selection of patients predisposed to CMAN for concomitant pathology, suspension of FANS or any other recognized nephrotoxic substance, the least amount of contrast media compatible with radiologic visualization of the patient's problem, careful hydration of the patient before contrast injection and sustained diuresis afterwards. The usefulness of pre-treatment with Ca-channel blockers or atrial natriuretic factors remains sub judice.
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PMID:[Physiopathology, clinical aspects and prevention of renal insufficiency caused by contrast media]. 917 67

Although heparin is better known as an anticoagulant, it also has several anti-inflammatory effects. Heparin is known to inhibit neutrophil adhesion, chemotaxis and oxygen free radical production. In addition, heparin is also known to act as an oxygen radical scavenger. Our hypothesis was that heparin would attenuate renal ischemia reperfusion injury. In this study, we investigated whether heparin had a protective effect on renal ischemia reperfusion injury. Sheep (n = 12) were prepared for the chronic study with venous, arterial and urinary catheters inserted. In addition, pneumatic occluders and ultrasonic flow probes were placed on renal arteries. After a 5-day recovery period, the sheep were randomized to either a heparin treatment group (400 IU/kg i.v. bolus 10 minutes before renal artery occlusion, followed by a continuous effusion 25,000 IU in 250 ml of 0.9% NaCl at 10 ml/hr, n = 6) or a control group (n = 6), which received an equivalent volume of 0.9% NaCl. All the sheep then underwent 90 minutes of bilateral renal ischemia followed by 24 hours of reperfusion. Blood urea nitrogen (BUN), serum creatinine (Scr), and creatinine clearance (CrCl) were determined at various intervals during both the ischemic and reperfusion periods. Kidney tissue samples were obtained at autopsy for histologic examination. As a result, there were significant differences in the degree of inflammation (1.50 +/- 1.24 Vs 0.50 +/- 0.79, P < 0.05) between the control and heparin treatment groups, but not in the degree of injury (2.83 +/- 0.44 Vs 2.33 +/- 0.28). In this study, heparin significantly attenuated polymorphonuclear leukocytes (PMNs) infiltration within the interstitium, but it did not affect the degree of renal damage as measured by urinary chemistries or renal tubular damage as assessed by histopathologic evaluation.
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PMID:Heparin attenuated neutrophil infiltration but did not affect renal injury induced by ischemia reperfusion. 925 12

It has already been shown that pulmonary injury is induced after intestinal or hind limb ischemia-reperfusion injury. The purpose of this study was to determine the effect of renal ischemia-reperfusion injury on the pulmonary system. We compared the pulmonary effects of 60 and 90 minutes ischemia followed by 24 hour reperfusion in sheep kidneys. Standard hemodynamic measurements, arterial and mixed venous blood gas analysis, urine output, creatinine clearance, and blood urea nitrogen concentration were measured at baseline, during ischemia and reperfusion periods. After 24 hours of reperfusion, animals were sacrificed and underwent autopsy with collection of samples for wet/dry lung-weight ratio, lung tissue conjugated dienes, and renal histology. As expected, renal ischemia resulted in an increased serum creatinine and blood urea nitrogen concentrations, decreased creatinine clearance, and histological evidence of renal damage. There was no evidence of pulmonary hypertension or hypoxemia during renal ischemia-reperfusion. There was also no significant difference in the wet/dry lung-weight ratios or lung tissue conjugated denies between the two ischemic groups (60 and 90 minutes) and nonischemic control group. These results suggest that renal ischemia-reperfusion injury was not associated with a significant degree of pulmonary dysfunction.
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PMID:Renal ischemia-reperfusion injury does not induce pulmonary dysfunction in sheep. 925 13

The present study was designed to investigate the effect of captopril, a sulfhydryl (-SH) containing ACE inhibitor and lisinopril, a non-SH containing ACE inhibitor, on ischaemia-reperfusion-induced renal injury in rats and to study the involvement of the free radical scavenging property of captopril in its renoprotective effect. Bilateral renal artery occlusion was induced for 30 min followed by reperfusion for 24 h. Blood samples were taken from retro orbital sinus before surgery and at 24 h after reperfusion for blood urea and blood creatinine estimation. After completion of 24 h of renal reperfusion the carotid artery was cannulated and the mean arterial blood pressure (MABP) was recorded. The left kidney was used for histological examination. The right kidney was utilised for estimation of mitochondrial thiobarbituric acid reactive substances (TBARS). Renal ischaemia, followed by reperfusion, significantly increased blood urea nitrogen (BUN) and blood creatinine. However, creatinine clearance decreased markedly. Captopril administered before renal artery occlusion or immediately after reperfusion and lisinopril pre-treatment significantly attenuated the increase in BUN and blood creatinine. Creatinine clearance was markedly better in captopril-treated animals as compared to lisinopril-treated rats. Captopril significantly decreased the degree of tubular necrosis, haemorrhagic streaks and urinary casts. Lisinopril treatment decreased tubular necrosis and urinary casts but no marked effect on haemorrhagic streaks was noted. Administration of captopril before ischaemia or just after reperfusion significantly reduced the elevated concentration of mitochondrial TBARS but no such decrease was noted in lisinopril-treated rats. Based on these results it may be concluded that captopril and lisinopril markedly protected against ischaemia-reperfusion-induced renal injury and any additional renoprotective effect of captopril may be ascribed to its free radical scavenging properties.
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PMID:Effect of angiotensin converting enzyme inhibitors on ischaemia-reperfusion-induced renal injury in rats. 950 76

50 Sprague-Dawley rats were used to study the effect of allopurinol and prostaglandin E1 (PGE1) on renal ischemia-reperfusion injury. They underwent left renal ischemia for 1 h and reperfusion. A right nephrectomy was performed, and 5 groups were made. Group AP received allopurinol 50 mg/kg and PGE1 20 micrograms/kg; group A, allopurinol; group P, PGE1; group C, control, and group S, sham group. Five animals from each group were used to study renal functions and 5 for renal histology. The serum creatinine values were lower in the treatment groups compared to the controls on days 1-3 and 7 (p < 0.05). The blood urea nitrogen values showed a similar trend. Maximum histological damage was seen in group C, followed by groups A, P and AP, in this order. We conclude that allopurinol and PGE1 attenuate renal ischemia-reperfusion injury in rats.
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PMID:Attenuation of renal ischemia-reperfusion injury in rats by allopurinol and prostaglandin E1. 956 43


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