Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcium channel blockers have been reported to preserve renal function when given prophylactically in animal models of acute renal failure (ARF), but the mechanism by which this effect occurs is unknown. We report that nitrendipine (NTR) ameliorates the decline in endogenous creatinine clearance when administered before to clamp-induced ischemia in rats (NTR + clamp, 0.21 +/- 0.06 ml/min; clamp alone, 0.13 +/- 0.04 ml/min, p less than 0.05). To determine whether this protective effect involves the proximal tubule, we compared the uptake of phosphate by brush border membrane (BBM) vesicles in NTR-pretreated ARF rats and in ARF rats pretreated with vehicle alone. A comparison of vehicle-pretreated/sham-operated and vehicle-pretreated/ARF rats served as a control. The initial uphill phase of Na+ gradient-dependent phosphate transport was significantly greater in NTR/ARF rats as compared with vehicle/ARF rats. Pretreatment with NTR did not affect BBM transport of D-glucose or proline. We conclude that NTR has a modest protective effect on overall renal function, and that preservation of proximal tubular function is probably part of this effect.
 ...
PMID:Modifications in proximal tubular function induced by nitrendipine in a rat model of acute ischemic renal failure. 248 64

UW (University of Wisconsin) solution, formulated by Belzer's team in Madison, has already been proved to increase cold ischemia time in liver and pancreas preservation. A multicentre clinical trial is being conducted to compare renal preservation in human transplantation using two different solutions: UW and Eurocollins (EC). This paper, whose results will be included in the multicentre trial, reports local comparative results between UW and EC perfused Kidneys. The two donor populations UW (28 cases) and EC (47 cases) were not randomized. They were however comparable in renal function prior to harvesting but not in age (35 +/- 13.4 years EC versus 27.7 +/- 12.4 years UW). The two recipient populations (48 EC versus 48 UW) were more homogeneous. Comparative results were significant with better graft function in the UW group: creatinine at one week: 499.2 +/- 296.3 EC versus 277.6 +/- 226.2 mumol/l, p less than 0.0001; creatinine at one month: 228.7 +/- 135 EC versus 159.7 +/- 135.6 mumol/l, p less than 0.02 and a decrease in acute tubular necrosis (39.5% EC versus 14.5% UW) and hospital stay. These results justify the use of UW solution by intraaortic flush especially during multi-organ procurement.
 ...
PMID:[Comparative study of the University of Wisconsin solution versus Eurocollins in kidney transplant]. 248 9

Oxygen free radicals have been implicated in the pathogenesis of tissue injury consequent to ischemia/reperfusion in several different organs, including heart, bowel, and kidney. In this study, the protective effect of FOY, SOD, and PEG-SOD against kidney damage resulting from warm ischemia and reperfusion was investigated in the rat. FOY (Gabexate mesilate), one of protease inhibitor, has been suggested to inhibit the activity of superoxide in polymorphonuclear leucocyte in recent reports. PEG-SOD (polyethyleneglycol-modified SOD), recently synthesized on the basis of SOD, has an additional value in comparison with SOD. WKA rats underwent right nephrectomy, and occlusion of the left renal artery, vein, and ureter for 60 minutes. FOY (50mg/kg, DIV.) was administrated from 5 minutes before reperfusion to 5 minutes after reperfusion to the rat. SOD (2mg/kg, 5mg/kg, 10mg/kg, IV.) and PEG-SOD (2mg/kg, 5mg/kg, IV.) were administrated at 10 minutes before reperfusion. 48 hours after operation, the measurement of urine output (60 minutes) was made, and BUN, Cr, K, UUN, UCr were measured at this point. Creatinine clearance was calculated from these results. The left kidney was removed and histological examination was performed. Serum BUN, Cr level were greatly elevated, and creatinine was diminished in the group of ischemic untreated rats (n = 8). In the groups of rats treated with FOY (n = 9), SOD (5mg/kg, 10mg/kg; n = 5, respectively), and PEG-SOD (2mg/kg, 5mg/kg; n = 5, respectively), serum Cr was significantly lower and creatinine clearance was significantly higher than control untreated group. Furthermore, tubular injury was less in histological examination in these groups.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Experimental study on renal protection against damage in kidneys subjected warm ischemia--protective effect of FOY, SOD, and PEG-SOD on ischemic acute renal failure]. 251 Nov 30

Although cyclosporine (CSA) is established in the prevention of allograft rejection, its use has been associated with dose-limiting toxicities, most notably to the kidney and liver. To date, the pathogenesis of the acute form of nephrotoxicity is unclear but may be related to inhibition of vasodilatory prostaglandins resulting in vasoconstriction and ischemia. The present study investigated the coadministration of CSA with a unique hemorheologic agent, pentoxifylline (PTX), in the murine model. A total of 48 rats were orally dosed with CSA 25 mg/kg for 10 days with either PTX 45 mg/kg i.p. or saline every 12 hr. Posttreatment renal function, assessed by creatinine (CCR) and inulin (CIN) clearances and renal electrolyte handling, was compared with baseline data and between groups. In an attempt to assess prostaglandin-mediated changes in enteral absorption, oral CSA pharmacokinetics with and without PTX were compared to the pharmacokinetics of similar groups (N = 8) administered i.v. CSA. Mean CIN of rats coadministered CSA and PTX (942 +/- 214 microliters/min/g KW) was similar to control rats 884 +/- 185 microliters/min/g KW); both were significantly greater than CSA alone (537 +/- 211 microliters/min/g KW; p less than .01). Likewise, percent of baseline CCR was significantly reduced in rats treated CSA (61 +/- 24%) compared to controls 113 +/- 41%) and rats coadministered PTX (117 +/- 75%; p less than .05). No differences in percent change from baseline electrolyte handling were observed among groups. Further, no differences in CSA pharmacokinetics with or without PTX were found.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Prevention of cyclosporine-induced nephrotoxicity with pentoxifylline. 251 44

Ischemic injury results in proximal tubule (PT) dysfunction and loss of surface membrane (SM) polarity. Since epithelial vectorial transport requires SM polarity, we set out to determine if correction of renal cortical PT dysfunction following ischemia was dependent on the reestablishment of SM polarity. Acute renal failure was induced using a bilateral 50-min pedicle clamp. Serum creatinine and fractional sodium excretion were maximal on day 1, remained elevated on day 3, and returned toward base line by day 8. PT cellular ultrastructure was normal by day 3. Despite rapid morphological recovery, ischemia resulted in a prolonged defect in glucose reabsorption. The delayed recovery of normal glucose handling closely paralleled the slow normalization of apical membrane lipid polarity. Na+-K+-ATPase polarity was also lost secondary to ischemia as demonstrated cytochemically and biochemically by the redistribution of Na+-K+-ATPase to the apical membrane. The time required to reestablish normal Na+-K+-ATPase polarity (8 days) paralleled the recovery of normal PT Na+ reabsorption (8 days), as assessed by fractional lithium clearances. This finding supports the hypothesis that apical Na+-K+-ATPase is in part responsible for reduced Na+ reabsorption following ischemic injury. In summary, these data suggest that functional recovery of PT glucose and Na+ reabsorption following a reversible ischemic insult requires not only morphological recovery, but also the reestablishment of surface membrane lipid and protein polarity.
 ...
PMID:Epithelial polarity following ischemia: a requirement for normal cell function. 253 79

Neutrophils have been implicated as central mediators in myocardial and skeletal muscle ischemia-reperfusion injury. This study tests whether these cellular elements and the chemoattractant leukotriene (LTB4) play a role in postischemic renal failure. Anesthetized rats underwent 45 min of left renal pedicle clamping. Five minutes after reperfusion, LTB4 levels were elevated to 1.42 ng/ml (P less than 0.05); thromboxane (Tx)B2 was 2,840 pg/ml, higher than 503 pg/ml in sham controls (P less than 0.05); renal artery blood flow was 67% of preclamping values at 1 min of reperfusion compared with 111% in sham (P less than 0.05). At 24 h, creatinine levels were 4.6 mg/dl (P less than 0.05). At 24 h, creatinine levels were 4.6 mg/dl (P less than 0.05); histology showed acute tubular necrosis (ATN). Neutrophil depletion by rabbit antiserum (n = 8) led during reperfusion to reduced LTB4 and TxB2 levels, 1.04 ng/ml and 1.043 pg/ml (P less than 0.05); increased renal blood flow of 174% (P less than 0.05); reduced creatinine levels of 1.8 mg/dl (P less than 0.05); and limited ATN. Pretreatment with diethycarbamazine prevented the increases in LTB4 and TxB2 (P less than 0.05), increased renal blood flow (P less than 0.05), minimized creatinine increase to 1.7 mg/dl (P less than 0.05), and reduced ATN. These data indicate that neutrophils and LTB4 play a role in ischemia-induced Tx synthesis and mediate postischemic renal injury.
 ...
PMID:Postischemic renal injury is mediated by neutrophils and leukotrienes. 254 28

In order to clarify the cause of the decrease in the urinary excretion of NAG (U-NAG) in severe ischemic renal injury in rabbits, we studied intrarenal energy metabolism in ischemic renal injury. After 5 min of ischemia, energy charge and ATP significantly decreased by 50% and 29% respectively. These parameters, however, did not significantly show the change in more than 5 min of renal ischemia. Energy charge and ATP did not reflect the degree of renal injury produced by ischemia, while it was indicated that the longer the period of ischemia until 120 min of ischemia, the less the rate of intrarenal ATP resynthesis at 30 min after reflow. Intrarenal lactate content increased significantly from the 5 min ischemia group to the 180 min. These results suggest that no improvement in intrarenal energy metabolism with increasing duration of renal ischemia is showed and ischemic renal injury develops progressively. It is probable that the decrease in U-NAG in severe ischemic renal injury is due to the inability of the kidney to wash out NAG into the urine, although NAG may be released from the injured tubular cells in proportion to ischemic renal injury. Therefore, in spite of severe ischemic renal injury, U-NAG may show low values, and may lead to misjudgement that the proximal tubular cells are intact. U-NAG should be measured repeatedly and estimated in association with the other renal function tests, especially creatinine clearance, for the correct evaluation of ischemic renal injury.
 ...
PMID:[Intrarenal energy metabolism in ischemic renal injury in rabbits]. 258 23

To determine the timing and location of renal cell regeneration after ischemic injury to the kidney and to assess whether exogenous epidermal growth factor (EGF) enhances this regenerative repair process to accelerate recovery of renal function, experiments were undertaken in rats undergoing 30 min of bilateral renal artery clamp ischemia followed by reperfusion for varying time intervals. Renal cell regeneration, as reflected by incorporation of radiolabeled thymidine within the kidney, began between 24 to 48 h and reached a peak at 72 h after renal ischemia. As demonstrated by histoautoradiography, renal thymidine incorporation was essentially confined to tubule cells. Morphometric analysis of histoautoradiograph sections of renal tissue demonstrated that the majority of labeled cells were found in renal cortex, but some labeled cells were also located in the inner stripe of the outer medulla, suggesting that injury to medullary thick ascending limbs also occurs in this ischemic model. Exogenous EGF administration produced increases in renal thymidine incorporation compared with non-treated animals at 24, 48, and 72 h after ischemic injury. This accelerated DNA replicative process was associated with significantly lower peak blood urea nitrogen (BUN) and serum creatinine levels, averaging 63 +/- 20 and 3.1 +/- 0.4 mg/dl in EGF-treated ischemic rats compared with 149 +/- 20 and 5.1 +/- 0.1 mg/dl, respectively, in nontreated ischemic rats, and was also associated with a return to near normal BUN and serum creatinine levels in EGF-treated animals approximately 4 d earlier than that observed in nontreated animals. This report is the first demonstration that EGF accelerates the repair process of a visceral organ after an injurious insult.
 ...
PMID:Epidermal growth factor enhances renal tubule cell regeneration and repair and accelerates the recovery of renal function in postischemic acute renal failure. 259 59

Preserved organs are damaged not only by the ischemic injury due to lack of oxygen. The reperfusion injury mediated by oxygen free radicals is an important factor in the postischemic organ failure. The prevention of free radical-induced reperfusion injury with allopurinol (AP) and superoxide dismutase (SOD) is shown in a warm ischemia kidney model. Rats were treated with allopurinol (40 mg/kg i.v.) one hour, or with SOD (20,000 IU/kg i.v.) one minute before reperfusion after a period of 35 minutes of warm ischemia. Allopurinol and SOD reduced significantly the postischemic kidney failure with a less important increase of creatinine. Creatinine levels on day three in the control group: 517 +/- 87 mumol/ml, in the SOD-group: 206 +/- 105 mumol/ml, and in the AP-group: 163 +/- 81 mumol/ml (anal. of variance: p = 0.0001). AP has a wide therapeutic range. We feel, that it is important to confirm the prevention of reperfusion injury by allopurinol prophylaxis clinically.
 ...
PMID:[Reduction of renal reperfusion damage following warm ischemia by allopurinol and superoxide dismutase]. 263 82

Ischemia-induced renal injury is prevented by inhibition of thromboxane (Tx) synthesis. This protection was believed to be secondary to a high prostaglandin (PG)/TxA2 ratio. This study tests whether increasing the PG/Tx ratio by administration of vasodilating PGs protects the reperfused ischemic kidney. Anesthetized rats underwent right nephrectomy and 45 minutes of left renal pedicle clamping. Beginning 10 minutes before clamp release, animals were treated intravenously with the following: saline placebo (n = 10); the cyclooxygenase inhibitor ibuprofen (Ibu), 12.5 mg/Kg in a bolus (n = 8); a stable analogue of prostacyclin (PGI2), 500 ng/kg/minute for 2 hours (n = 9); PGE1, 400 ng/kg/minute for 2 hours (n = 8); the combination Ibu and PGI2 (n = 8) or PGE1 (n = 8). In saline treated ischemic controls, 5 minutes after reperfusion plasma, thromboxane (TxB2) and 6-keto-PGF1 levels were 2537 and 317 pg/ml, respectively--higher than the TxB2 and 6-keto-PGF1 levels of 750 and 80 pg/ml, respectively, in nephrectomized but nonischemic sham controls (n = 7) (p less than 0.05). In ischemic control animals at 24 hours, creatinine levels were 4.6 mg/dl, relative to 0.9 ml/dl in sham animals (p less than 0.05); the weight of the left (L) ischemic kidney relative to the right (R) normal kidney was 118%, compared with 99% in sham animals (p less than 0.05); and renal histology of ischemic control animals at 24 hours showed acute tubular necrosis (ATN) relative to normal findings in sham animals. Pretreatment with Ibu led to: TxB2 and 6-keto-PGF1 levels of 116 and 40 pg/ml, lower than those of sham animals (p less than 0.05); creatinine levels of 4.6 mg/dl, L/R renal weight of 119%; and ATN similar to that of ischemic controls. Treatment with a PGI2 analogue or PGE1 was not protective and led to increases in TxB2, 6-keto-PGF1, creatinine, L/R renal weight, and ATN similar to that of ischemic controls. The combination of Ibu and either PGI2 or PGE1 led to: reduced levels of TxB2 and 6-keto-PGF1 (p less than 0.05); attenuated increases in creatinine to 2.2 and 2.3 mg/dl, respectively (p less than 0.05); and limited ATN (p less than 0.05). These data indicate that the vasodilating PG protect the ischemic reperfused kidney only when Tx is inhibited.
 ...
PMID:Vasodilating prostaglandins attenuate ischemic renal injury only if thromboxane is inhibited. 264 99


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>