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)

Previous experimental and human data suggests a detrimental effect on the course of acute renal failure related to exposure of blood to artificial dialysis membranes of poor biocompatibility. We performed a 2.5-year prospective randomized trial to compare the clinical course of acute renal failure (post-operative ischemic acute tubular necrosis, ATN) in patients receiving a cadaveric renal transplant requiring supportive hemodialysis in the immediate post-transplant setting. Patients were randomized to either a cuprophane or polymethylmethacrylate (PMMA) conventional hollow fiber dialyzer. All patients received a standard immunosuppressive regimen which included induction therapy with either horse anti-thymocyte gamma globulin (ATGAM) or the murine anti-CD3 monoclonal antibody (OKT3). Of 53 patients randomized, 17 were excluded (2 for intervening biopsy-proven rejection prior to recovery from ATN, 10 for primary graft nonfunction and 5 for other reasons), leaving 36 evaluable cases of uncomplicated ATN, 18 in each group. There was no difference by age, race, gender, cause of ESRD, immunosuppressive regimen, cold or warm ischemia time, use of pre-transplant dialysis, percent oliguria or the incidence of intra-dialytic hypotension between the 2 groups. There was no difference in the mean time to recovery from ATN posttransplant (8.9 days in the cuprophane group vs 9.5 days in the PMMA group, p = NS) or in the average number of hemodialysis treatments required (3.6 in both groups, p = NS). There was also no difference in long term allograft outcome in terms of the nadir serum creatinine, the number of episodes of subsequent acute rejection or in the development of chronic rejection. An intent-to-treat analysis of all 53 originally randomized patients similarly yielded no significant differences. A subsequent, non-randomized study using a membrane of intermediate biocompatibility (Hemophan) also showed no difference in recovery time from ATN. Bioincompatible membranes do not seem to have a significant clinical impact on the course of recovery of this form of acute renal failure. The striking benefits of biocompatibility in the course of ARF seen in other human trials may relate more to the non-renal systemic toxic effects of bioincompatibility.
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PMID:Biocompatible dialysis membranes and acute renal failure: a study in post-operative acute tubular necrosis in cadaveric renal transplant recipients. 898 57

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

In order to evaluate the role of underlying disease in the high mortality observed in acute renal failure (ARF) and risk factors related to the development of oliguric ARF in renal allograft recipients, two groups were selected: 34 patients with native kidneys, aged 16 and 57 years, and presenting ischemic ARF caused by cardiovascular collapse, with no signs of infection at the time of diagnosis; and 34 renal allograft recipients who developed ARF immediately after transplantation, without rejection. ARF was defined either as 30% increase of basal plasmatic creatinine in patients with native kidneys or nonnormalization of plasmatic creatinine at day 5 after transplantation in renal allograft recipients; oliguria as diuresis < or = 400 mL/24 h. There were no differences in age, male frequency, oliguria presence and duration, need for dialysis, and infection episodes for renal allograft recipients and patients with native kidneys. The development of sepsis (3% and 41%) and death rate (3% and 44%) were higher in patients with native kidneys (p < 0.01). The renal allograft recipients with both oliguric (n = 18) and nonoliguric (n = 16) ARF were evaluated and no difference was observed in the recipient's age, donor's age, cold ischemia time, time elapsed until plasmatic creatinine normalization, donor's plasmatic creatinine or urea, and mean arterial pressure. No differences were observed between the groups regarding frequency of infection episodes during ARF and frequency of death. In conclusion, renal allograft recipients presented a lower death rate and were less susceptible to sepsis. Cold ischemia time, age, and hemodynamic characteristics of the donor did not affect the development of oliguria.
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PMID:Acute renal failure in renal allograft recipients and patients with native kidneys. 910 1

Propranolol has been shown to be effective for as long as 5 days in massively burned children to reduce heart rate and cardiac work. This article describes the use of propranolol given for 10 days to burned children to test whether the drug remains effective and safe in reducing heart rate and cardiac work for longer periods. We prospectively studied 22 children, 1 to 10 years of age with burns covering > or = 40% of their total body surface area. These children were treated with 0.5 to 1.0 mg/kg propranolol given orally or intravenously every 8 hours for 10 days. In both septic and nonseptic patients, propranolol significantly decreased their daily average heart rate (between 10% and 13%, p < 0.05) and rate-pressure product (between 10% and 16%, p < 0.05) compared with their 24-hour mean before propranolol treatment. No significant change in mean arterial blood pressure, or plasma urea nitrogen creatinine or glucose levels could be shown. No hypotension, hypothermia, azotemia, hyperglycemia or hypoglycemia, arrhythmia, bronchospasm, or peripheral ischemia was noted during or after treatment. Whereas propranolol lowered heart rate more per milligram per kilogram body weight when given intravenously, both routes were safe and effective. From these data, we conclude that propranolol can be given to decrease the work of the heart safely and effectively for > or = 10 days.
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PMID:Prolonged use of propranolol safely decreases cardiac work in burned children. 916 45

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

In previous studies on experimental renal failure, hypertrophy of cardiomyocytes, diminished capillarization, and increased intercapillary distances had been observed, abnormalities that will expose the heart to reduced ischemia tolerance. It has not been established, however, whether such structural alterations are unique for the heart (eg, as a consequence of left ventricular hypertrophy) or are demonstrable in other tissues as well. Clarification of this point is important to test hypotheses on some potential mechanisms for cardiac undercapillarization. To address this issue further, we compared capillary length density (by stereologic techniques) in perfusion-fixed skeletal muscle (m. psoas) and hearts of subtotally nephrectomized (SNX) rats with moderate renal failure to those in sham-operated pair-fed controls. The duration of renal failure was 8 weeks. SNX rats had significantly higher mean systolic blood pressure (128 mm Hg v 109 mm Hg), serum creatinine, and urea levels. Despite pair feeding, the mean body weight was significantly lower in the SNX rats (409 g v 471 g), but the left ventricular weight to body weight ratio tended to be higher than in the sham-operated controls (2.39 mg/g v 2.13 mg/g). In the heart, myocyte mean cross-sectional area (675 +/- 112 microm2 v 545 +/- 111 microm2) and volume density of nonvascular interstitial tissue (3.47 +/- 1.04 v 1.33 +/- 0.22) were significantly higher in the SNX rats than in the controls. In parallel, myocardial capillary length density was significantly reduced after subtotal nephrectomy (3,036 +/- 535 mm/mm3 v 3,916 +/- 615 mm/mm3). In contrast, in skeletal muscle, myocyte cross-sectional area (3,109 +/- 783 microm2 v 3,042 +/- 639 microm2), capillary length density (718 +/- 248 mm/mm3 v 717 +/- 184 mm/mm3), and three-dimensional capillary fiber ratio (2.10 +/- 0.26 v 2.13 +/- 0.4) were similar in SNX and control rats. These data document a selective defect of capillarization in the heart of animals with moderate renal failure, pointing to tissue-specific abnormalities of cardiac capillarogenesis.
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PMID:Rats with moderate renal failure show capillary deficit in heart but not skeletal muscle. 929 67

After cardiac surgery, transient renal dysfunction often occurs. The main reasons for impairment of renal function are intraoperative hypotension, ischemia/reperfusion injury and inflammatory response to cardiopulmonary bypass (CPB). Pentoxifylline is known to have anti-inflammatory properties. Gamma-hydroxybutyrate (GHB), an endogenous regulator of energy metabolism, showed beneficial effects on experimental intestinal ischemia/reperfusion injury and liver graft function. Both drugs may be of practical interest in diminishing renal damage during and after cardiac surgery. After approval by the ethics committee and informed consent, 45 patients for elective coronary artery bypass grafting with no clinical and laboratory impairment of renal function were randomized into 3 groups (15 patients each): group 1 received saline as control, group 2 received pentoxifylline intraoperatively (1 mg/kg/h after a priming dose of 1 mg/kg) and group 3 received GHB intraoperatively (25 mg/kg/h after a priming dose of 25 mg/kg) in a double-blinded fashion. During 3 periods (before CPB, from the beginning of CPB until the end of surgery, 24 hours postoperatively), glomerular (creatinine clearance, CCr) and tubular markers of renal function (beta-NAG, alpha 1-microglobulin) were detected in addition to clinical routine standards (creatinine, urea, fractional excretion of sodium). Changes in glomerular and in tubular function were comparable in all groups without characteristic effects of either GHB or pentoxifylline. With CPB, CCr decreased significantly until the end of operation, but showed a rise to preoperative levels on the first day after operation. Tubular function markers (beta-NAG, alpha 1-microglobulin, related to simultaneous excretion of creatinine) showed a remarkable rise after the beginning of CPB up to the postoperative period. The results of the present pilot study suggest the detection of tubular proteins and enzymes a useful addition to present routine clinical standards for recognizing early intraoperative changes in renal function. In the patients studied, there were no clinical signs of renal dysfunction. Neither GHB nor pentoxifylline--in the doses applied--was able to show a therapeutic benefit despite the theoretical advantages.
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PMID:[Effect of gamma-hydroxybutyric acid and pentoxifylline on kidney function parameters in coronary surgery interventions]. 937 42

We conducted a prospective case series study to investigate the causes of and factors influencing morbidity and mortality in 102 consecutive patients after elective infrarenal abdominal aneurysm (AAA) surgery between 1992 and 1995. Preoperative factors (demographics, risk factor indexes, electrocardiographic findings, ejection fraction, and stress imaging scans were indicated) and intraoperative factors (duration of surgery, size of aneurysm, complications, units of blood transfused, and additional procedures performed) were recorded. Patients were admitted to the intensive care unit (ICU) for at least 24 hours and followed for 30 days postoperatively. The mortality rate was 4.9%, due in all cases to multiorgan dysfunction syndrome (MODS). Death was preceded by colon ischemia (two patients), intraabdominal bleeding (two patients), or sepsis (one patient). Only the preoperative blood urea nitrogen correlated with mortality (p = 0.042). Complications occurred in 59% of patients in the ICU and involved the cardiovascular system in 83% of them (heart rate > 90 bpm in 49%). On multivariate analysis, only duration of surgery was associated with ICU complications (p = 0.018). No complication resulted in mortality. Ward complications occurred in 13%, and 5% of these patients required readmission to the ICU. Although cardiac complications are considered the major cause of mortality after infrarenal AAA surgery, all five deaths in the present series were due to MODS. Preoperative screening should be more selective, and intraoperative and postoperative care should be stressed.
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PMID:Outcome after elective infrarenal aortic aneurysm surgery. 949 20

The effect of ginsenoside-Rd in ischemic-reperfused rats was examined. In control rats, blood and renal parameters and the activities of antioxidative enzymes in renal tissue deviated from the normal range, indicating dysfunction of the kidneys. In contrast, when ginsenoside-Rd was given orally for 30 consecutive days prior to ischemia and reperfusion, the activities of the antioxidation enzymes superoxide dismutase, catalase and glutathione peroxidase were higher, while malondialdehyde levels in serum and renal tissue were lower in the treated rats than in the controls. Decreased levels of urea nitrogen and creatinine in serum demonstrated a protective action against the renal dysfunction caused by ischemia and recirculation. On the other hand, it was demonstrated that ginsenoside-Rd affected cultured proximal tubule cells subjected to hypoxia-reoxygenation, probably by preventing oxygen free radicals from attacking the cell membranes.
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PMID:A study of ginsenoside-Rd in a renal ischemia-reperfusion model. 949 38


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