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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments were performed on rats subjected to renal ischemia and various treatment procedures to determine the origin and functional consequences of vascular obstruction. To this end, its occurrence and severity was assessed qualitatively and quantitatively in the outer medulla, where it is particularly prominent. The incidence of medullary hyperemia was not influenced by inhibiting thrombocyte aggregation with 5 or 70 mg/kg of acetyl salicylic acid or preventing fibrin deposition with 100 IE/kg of heparin before ischemia, and these substances produced no improvement renal function. The incidence and degree of hyperemia, however, could be substantially reduced or completely eliminated by acutely raising blood pressure after ischemia or by decreasing the number of circulating erythrocytes before ischemia. These procedures were effective in raising filtration rate and tubular reabsorption from 20% to 60% of normal, in restoring renal blood flow and vascular resistance to completely normal, and in diminishing epithelial damage both three and 18 hours after ischemia. The following conclusions are drawn: first, vascular obstruction, which is not lessened by inhibiting thrombus formation but is easily reversed or prevented by raising perfusion pressure or decreasing hematocrit, is probably caused by erythrocyte aggregation during ischemia. Second, vascular obstruction, which appears to raise renal vascular resistance and lower blood flow and filtration rate, cannot be limited to the medulla but must also be present in the cortex. Finally, reversing or preventing vascular obstruction can fully restore renal perfusion, partially restore glomerular and tubular function, greatly reduce tubular necrosis and thus prevent renal failure.
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PMID:The contribution of vascular obstruction to the functional defect that follows renal ischemia. 356 Jun 46

Pretreatment with the thromboxane synthase inhibitor OKY-046 but not the cyclo-oxygenase inhibitor ibuprofen protects against ischemia-induced acute tubular necrosis. However, ibuprofen together with the vasodilating agent prostaglandin E1 is protective. This suggests that a high prostaglandin to thromboxane ratio is the major factor operative in preventing tubular necrosis, the subject of this study. Rats that had unilateral nephrectomy (n = 60) with the exception of rats that had sham operations (n = 8) underwent 45 minutes of left renal pedicle clamping. Thirty minutes before the operation, the rats received either a saline solution or a thromboxane synthase inhibitor that was given intravenously. The inhibitors OKY-046 (2 milligrams per kilogram, n = 10), UK38485 (1 milligram per kilogram, n = 9) and U63357A (10 milligrams per kilogram, n = 10) were given as a single bolus while the inhibitor CGS13080 (0.1 milligram per kilogram, n = 9, and 1.0 milligram per kilogram, n = 7) was given by constant infusion and continued for 60 minutes after reperfusion. With saline solution therapy, five minutes after reperfusion, thromboxane B2 increased from 154 to 2,537 picograms per milliliter (p less than 0.00001) and 6-keto-prostaglandin F1 alpha increased from 51 to 266 picograms per milliliter (p less than 0.004). At 24 hours, the creatinine level increased from 0.5 to 2.8 milligrams per deciliter (p less than 0.00001). Only OKY-046 yielded a creatinine level at 24 hours of 1.2 milligrams per deciliter, a value lower than that for those in the saline solution control group (p less than 0.002). Furthermore, OKY-046 led to the highest prostaglandin to thromboxane ratio (p less than 0.035). The five other ratios which occurred after drug therapy were inversely related to the decrease in the creatinine value (r = -0.93, p less than 0.02). Histologically, OKY-046 was the only thromboxane synthase inhibitor to prevent acute tubular necrosis (p less than 0.05). Results show that a high prostaglandin to thromboxane ratio protects against acute tubular necrosis.
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PMID:A high plasma prostaglandin to thromboxane ratio protects against renal ischemia. 367 99

Sprague-Dawley rats were injected with known nephrotoxic doses of tobramycin and then subjected to varying amounts of warm renal ischemia. Analysis of serum creatinine at the time of sacrifice revealed no statistically significant difference among controls and the two doses of tobramycin at any given duration of ischemia. Light microscopy revealed no worsening of tubular necrosis with increasing doses of tobramycin.
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PMID:Tobramycin and renal ischemia. 378 4

Since prostacyclin (PGI2) is known to regulate renal cortical blood flow and since ischemia stimulates thromboxane (Tx) A2 synthesis, the role of these prostanoids in moderating the response to renal ischemia was studied in the rat. At baseline, plasma TxB2 concentration in untreated animals (n = 13) was 357 pg/ml. The left renal pedicle was clamped for 45 minutes after a right nephrectomy (n = 16), which led after 5 minutes of reperfusion to a rise in TxB2 to 2825 pg/ml (p less than 0.001), but there was no change in 6-keto-PGF1 alpha. After 24 hours creatinine levels rose from 0.4 to 3.0 mg/dl (p less than 0.001), and left renal weight rose from 94% to 117% (p less than 0.001) relative to the weight of the right kidney. In nephrectomized but nonischemic sham control rats (n = 7), creatinine level was 0.9 mg/dl and kidney weight 91% after 24 hours. Pretreatment with OKY 046 (n = 13) (2 mg/kg administered intravenously) blocked ischemia-induced TxB2 synthesis, while 6-keto-PGF1 alpha levels rose from 96 to 302 pg/ml (p less than 0.001). There was no increase in creatinine levels or kidney weight relative to the sham group. Pretreatment with ibuprofen (n = 10) (12 mg/kg) or OKY 046 and ibuprofen (n = 9) inhibited TxB2 and 6-keto-PGF1 alpha synthesis, but creatinine levels and renal weight rose (p less than 0.001). Renal histology in OKY 046-pretreated animals was equal to that in nephrectomized controls, while all other ischemic groups showed tubular necrosis. Results indicate that a high PGI2/TxA2 ratio protects against renal ischemia.
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PMID:Prostacyclin and thromboxane A2 moderate postischemic renal failure. 389 35

Variable degrees of injury of the pancreatic islets of Langerhans, with sparing of the acinar pancreas, were observed in three infants (age range, 1 day to 3 months) who died of profound shock. The duration of shock varied from 19 to 48 hours. In two of the infants, the shock stemmed from hypovolemia; in the remaining infant, the shock followed blood loss, sepsis, and heart failure. The islet lesions were devoid of cellular infiltrates, hemorrhage, and fibrin thrombi. Tissue manifestations of shock included acute renal tubular necrosis, massive hepatic centrilobular necrosis, ischemic enteropathy, and "shock" lung. Study of pancreatic sections from 30 children (age range, 13 hours to 15 years) with clinical and/or morphologic evidence of shock showed no additional instances of islet injury. These findings suggest that pancreatic islets in the young may be vulnerable to shock-induced ischemia. Studies are in progress in an animal model to test this hypothesis.
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PMID:Shock-related injury of pancreatic islets of Langerhans in newborn and young infants. 390 77

In this investigation, we describe a modification of Euro-Collins flushing solution which enables this solution to be effective in preventing normothermic postischemic acute renal failure. The left kidneys of Sprague-Dawley rats were briefly flushed in situ by vascular perfusion with Euro-Collins solution and the renal pedicle clamped to render the kidney ischemic and hold the flushing solution in the kidney. Following 1 h of in situ normothermic ischemia, the pedicle clamp was removed and a contralateral nephrectomy of the right kidney performed. In two other groups of rats the same experimental protocol was followed using Euro-Collins solution in which the dextrose in this solution was replaced with a similar osmolal contribution of either sucrose (64 g/l) or mannitol (35 g/l). Rats with kidneys flushed with the standard Euro-Collins solution containing dextrose (n = 24) exhibited significantly higher postischemic daily serum creatinine levels, a greater degree of tubular necrosis, and a higher mortality (75, versus 31%) than unflushed ischemic controls (n = 22). Rats with kidneys flushed with Euro-Collins, containing either sucrose (n = 25) or mannitol (n = 22) in place of dextrose, all survived, exhibited only focal tubular damage as observed by electron microscopy, and most returned to normal serum creatinine levels within 72 h following ischemia. These findings, together with other reports that mannitol- and sucrose-based flushing solutions provide excellent protection during prolonged cold ischemia, strongly argue for the substitution of sucrose, mannitol or other similar protective impermeant agents for dextrose in flushing solutions such as Euro-Collins.
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PMID:Improving Euro-Collins flushing solution's ability to protect kidneys from normothermic ischemia. 393 Sep 35

The protective effect of intravenous administration of exogenous prostaglandin E1 on ischemia-induced acute renal failure was investigated in dogs. The parameters studied were renal cortical blood flow, renal function, survival time, and histologic changes. The model was prepared by clamping the renal artery for 1 or 2 hours. Renal cortical blood flow was measured by the hydrogen washout technique. After prostaglandin E1 administration, renal cortical blood flow increased significantly and renal function was maintained at relatively high levels with low serum creatinine and moderate creatinine clearance levels. Mean survival time increased markedly from 4.1 to 35.2 days by administration of prostaglandin E1. Ischemia-induced acute renal failure is usually accompanied by zonal necrosis of renal tubules prominent in the cortex. However, occurrence of these histologic damages could be virtually prevented by prostaglandin E1 administration (i.e., only minimal tubular necrosis was found in a small area of the cortex). We conclude from this study that postischemic administration of exogenous prostaglandin E1 does provide a certain degree of protection for the kidney, which may have a great clinical implication in improving the success rate of kidney transplantation, especially of cadaver donor kidneys.
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PMID:Protective effect of prostaglandin E1 on ischemia-induced acute renal failure in dogs. 404 Feb 71

A study was made of the acute and chronic (15 days) functional and morphologic effects on the rat kidney of warm ischemia and contralateral nephrectomy, in order to define a suitable animal model for testing renal transplant preservation techniques when warm ischemia is a contributing factor. Spontaneous recovery from 30-min warm ischemia was complete, and the model was consequently unsuitable; the high mortality from 90 min was unacceptable. Warm ischemia of 60 minutes produced severe renal tubular necrosis, an acceptable mortality, residual morphologic damage, and impairment of isolated kidney perfusion parameters at 15 days. Renal function in vivo was normal in many of these animals, despite appreciable residual morphologic changes, and it is evident that functional data alone are not sufficient for assessment of preservation regimens.
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PMID:An experimental model for assessment of renal recovery from warm ischemia. 634 Feb 72

The tubular necrosis produced by transient unilateral ischemia, three toxic cephalosporins, and the aminoglycoside neomycin were studied separately and in different combinations in the rabbit kidney. It was found that (1) mildly damaging transient ischemia (25 min) and a minimally toxic dose of the rapidly secreted cephalosporin cephaloglycin (60 mg/kg of body weight) are synergistically damaging; (2) there is no synergy between ischemia and the nonsecreted cephalosporin cephaloridine (90 mg/kg); and (3) ischemia and neomycin (100 mg/kg per day for three days) are not additively damaging, but the aminoglycoside has an additive effect with the combined insults of ischemia and cefazolin (500 mg/kg). Studies of transport showed that ischemia potentiates cephalosporin toxicity probably because it increases postischemic antibiotic concentrations in proximal tubular cells and that this increased uptake is the result of transiently augmented tubular secretion. Although this ischemic protocol reduced inulin clearance by 40%, it increased cephaloglycin secretion by an amount more than sufficient to overcome the decrease in filtration.
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PMID:Interaction of ischemic and antibiotic-induced injury in the rabbit kidney. 682 49

Acute renal failure (ARF) is related to reversible tubular necrosis, usually caused by ischemia or toxic substances. Our knowledge of the pathophysiology of ARF stems from the study of animal models which reproduce either an ischemic or a toxic form of ARF. Classical studies using microdissection and micropuncture have characterized the salient mechanisms of ARF: vascular compromise with hypoperfusion and decrease in glomerular filtration rate, and tubular insult with cell necrosis and high intratubular pressure. More recent studies have emphasized the cellular and molecular events occurring during the course of ARF, including changes in cytoskeleton and matrix proteins, apoptosis and the role of Heat Shock Proteins. Endothelin and growth factors such as epidermal growth factor or hepatocyte growth factor seem to be important mediators in the regeneration phase of ARF. In various animal models, EGF, HGF or antagonists of endothelin receptors have a protective effect on renal function. These findings may be of clinical relevance, and suggest future therapeutic approaches in the treatment of ARF.
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PMID:[Experimental models of acute kidney failure]. 756 87


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