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

Canine kidneys (n = 17) were flushed with COLLINS (C2), SACKS II, LAMBOTTE (KMgS), ROSS (hypertonic citrate), or RINGER glucose-mannitol solution following a 30-min period of normothermic ischemia. After 24 h hypothermic preservation with retrograde oxygen persufflation (ROP) and autotransplantation, the immediate functional recovery was determined using inulin and PAH clearance methods and compared with the normal contralateral kidney. While a good functional recovery was found in the COLLINS group, significantly exceeding results from hypothermic ischemic storage preservation, in experiments using other flush solutions ROP preservation resulted in only a small immediate function. Thus the experiments indicate that COLLINS solution C2 is the optimal flush solution for ROP preservation.
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PMID:[Hypothermic storage under aerobic conditions--the effect of different flushing solutions on kidney functional recovery]. 37 90

123 kidneys of mongrel dogs were stored under hypothermic conditions in Collins or Sacks solutions for 12 up to 72 h and then transplanted. Before preservation the kidneys were subdued to 0-30 min warm ischemia. Kidney function after transplantation was measured by PAH-and inulin-clearances. Successful 24 h preservation was likewise possible with Collins and Sacks solutions if there was not any warm ischemia. Kidney function was reduced by the length of preservation, according to the formula; y = 166.02 . e-0,125x (y = PAH-clearance and x = preservation time). With both solutions the most attainable preservation time after 15 min warm ischemia was only 12 h, longer preservation time or ischemic periods were not tolerable. However, the function of the ischemically damaged organ was significantly better preserved by Sacks solution in comparison with Collins solution-although the preservation period could not be extended by this solution. Therefore, as far as human kidney preservation is concerned, Collins solution should be replaced by Sacks solution.
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PMID:[Kidney preservation by hypothermic storage in Collins and Sacks solutions: the influence of 0-30 min of warm ischemia on the available preservation period (author's transl)]. 67 38

In unilateral nephrectomized beagle dogs the remaining kidney was subjected to 2 hrs of ischemia in situ. The ischemic organ was cooled to 22--23 degrees C by initial hypothermic perfusion over a 5-F catheter introduced into the renal artery via the carotid artery. It was then left in the open abdominal wound without any further attempts of cooling. Three perfusates were used: an isoosmolar Dextran solution (Eisenberger), a hyperosmolar, "intracellular" electrolyte solution (Sacks), and a hyperosmolar, "extracellular" electrolyte solution. There was a mean postoperative increase in serum creatinine levels of 0.6 mg-%. By the 3rd p.o. day at latest the serum creatinine was again within normal limits. The inulin and PAH clearances on the 7th and 14th p.o. day showed no significant differences to preoperative determinations. No definite advantage or disadvantage was noted among the three perfusates. All control dogs whose kidneys were made ischemic for 2 hrs without perfusion died due to acute tubular necrosis. Apparently the homogenous cooling and flushing by the initial perfusion is of more importance for good preservation in this situation than the composition of the perfusate.
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PMID:[Short time in-situ preservation of the ischemic kidney by a simple initial hypothermic perfusion with various cold solutions. An animal experimental study]. 115 70

Previous studies by others have shown that transplanted rat kidneys have abnormally low clearances of paraaminohippuric acid, inulin, and creatinine, due to rejection and/or to warm-ischemia-induced injury. In the present studies, randomly bred Sprague-Dawley rats were used as donors and recipients. The left kidneys of recipients were removed, and the right kidneys were left intact. Donor kidneys were flushed with an ice-cold hypertonic solution (150 mM NaCl, 200 mM mannitol, pH 6.4), and the kidneys were kept cold during surgery. Renal function was assessed 1 week later. The left transplanted kidneys in untreated recipients exhibited morphologic evidence of rejection, and the clearances of PAH and inulin were approximately 50% of those of the right native kidneys. CsA-treated rats did not reject the transplants, and the PAH and inulin clearances of the left transplanted kidneys were identical to those of the right native kidneys. Untreated and CsA-treated rats with both native kidneys intact served as controls. The amount of CsA given during the 7-day period produced no measurable change in renal function. This is the first demonstration of virtually normal hemodynamics in transplanted rat kidneys when randomly bred animals are used as donors and recipients. Moreover, the results indicate that if both rejection and warm ischemia are avoided, the presence of a functioning native kidney does not have a detrimental effect on the function of a transplanted kidney.
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PMID:Kidney transplants in cyclosporine-treated Sprague-Dawley rats. 230 Oct 33

To study the protective effect of 1,6-diphosphate fructose (FDP) on acute ischemia damage in brain, heart and liver, we observed its effect on acute ischemic renal failure (AIRF). AIRF in male Wistar rats was produced by renal arterial clamping for 45 minutes and reperfusion for 90 minutes. The rats were divided into 4 groups according to their age and FDP therapy: G1: young (3-4 months) AIRF rats without FDP; G2: old (26-27 months) AIRF rats without FDP; G3: young AIRF rats with FDP (0.5g/kg) i.v. infusion; G4: old AIRF rats with FDP. Inulin clearance (CIn), PAH clearance (CPAH), urinary sodium (UNA) were examined before ischemia and 30, 60 and 90 minutes after reperfusion. After reperfusion for 90 minutes, renal cortex was taken for the examination of renal mitochondrial ATP synthetic content (miATPs). CIn and CPAH were lower in G2 than in G1 (0.24 +/- 0.12 vs. 1.75 +/- 0.79, P < 0.01; 0.87 +/- 0.42 vs 7.12 +/- 4.04, P < 0.05, at 90 minutes reperfusion). CIn and CPAH in G1 showed an auto-recovery up to 40.1% and 33.7% of the level in contrast to G2. In G3 and G4 original FDP infusion resulted in a significant increase in miATPs and CIn (609 +/- 145 vs 389 +/- 97; 569 +/- 77 vs 338 +/- 61, P < 0.02; 2.47 +/- 0.58 vs 1.75 +/- 0.79, 1.29 +/- 0.42 vs 0.24 +/- 0.12, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Protective effect of 1,6-diphosphate fructose in ischemic renal failure in elderly rats]. 803 87

Acute ischemic renal failure is of great clinical importance because of its frequent occurrence and the high mortality it causes. Recent observations indicate that reperfusion has its own dangers because of oxygen-derived free radicals. To study this problem, ischemia was evoked in dogs in one kidney, by clamping the left renal artery for 45 min. This was followed by a 90-min period of reperfusion when diuresis, GFR, PAH clearance and sodium and potassium excretion were studied. Besides a control group (n = 6), the following treatment groups were investigated. Allopurinol (n = 7): 50 mg/kg for two days p.o. and 50 mg/kg in physiological saline infusion during the experiment; a small dose of SOD (n = 6): 0.5 mg/kg in infusion, started 1 min before reperfusion and given continuously for 10 min; and a high dose of SOD (n = 7): 5 mg/kg as above. In the first 15 min following reperfusion, the renal functions significantly worsened in all groups. Later on, the renal functions gradually improved and in the last period after reperfusion, GFR in the ischemic kidney was 64%, cPAH 59%, diuresis 60% and sodium and potassium excretion were 65% and 76%, respectively, of the basal values in the control group. Treatment with free radical scavengers did not cause any considerable changes in the renal functions. In some respects, the worst results were observed with low-level SOD treatment (cPAH, diuresis, as well as sodium and potassium excretion). At the end of reperfusion, there was a significant drop in sodium excretion by the right (intact circulation) kidney of the treated animals.
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PMID:Lack of effect of antioxidant therapy during renal ischemia and reperfusion in dogs. 845 8

A pig kidney perfusion model aimed for use in immunological and physiological xenotransplantation research has been developed. Organ viability was characterised by clearance studies, functional response to hormones/diureticum and by light microscopical examination. The pig kidney was perfused in a specially designed plexiglass chamber, using a roller pump and a small membrane oxygenator (O2/CO2, 95/5). The recirculating perfusate used was autologous pig blood diluted by Tyrodes solution to a hematocrit of 30%, at a total starting volume of 600-650 ml. The temperature was 37 degrees C. It was crucial for good organ function that the nephrectomy operating time, as well as the warm (1-2 min) and cold ischemia (average 43 min) times were minimized. The average total perfusion time was 151 minutes. Physiological parameters were measured during 10-15 minute periods at average times of 40, 63, 88 and 142 minutes. The clearance values of inulin in these periods were 54 +/- 13, 59 +/- 15, 48 +/- 23, 27 +/- 5 and for PAH; 103 +/- 14, 121 +/- 14, 106 +/- 30, 114 +/- 34 ml/min/100 g tissue weight. The plasma flows were 123 +/- 12, 155 +/- 17, 136 +/- 36 and 206 +/- 57 ml/min/100 g. The injection of 0.5 micrograms of alpha ANP to the perfusate resulted in a significant decrease in vascular resistance, and increase in urine production (+107%), as well as sodium (+112%) and potassium (+46%) excretion. Ten mg furosemide doubled the urine production and sodium excretion, while potassium excretion increased marginally. The number of leucocytes decreased by 39% during the perfusion, while the platelet count was unaffected. Light microscopy of the renal tissue after termination of the experiments revealed endothelial damage to variable extent. Loss of endothelial cells was most obvious at the level of arcuate and interlobular arteries, while the endothelium was intact in larger arteries and veins. Accumulation of polymorphonuclear granulocytes was found predominantly in the peritubular vessels, and to a lesser degree in the cortical venules. In the tubular cells, only minimal epithelial swelling and irregular cytoplasmic vacuolisation was found. Thus, a good functional viability can be maintained during 2 hours in vitro perfusion, although a decline in function as well as structural damage can be seen at the end of the experiment.
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PMID:Physiological and histological characterisation of a pig kidney in vitro perfusion model for xenotransplantation studies. 883 54

Renal ischemia/reperfusion (I/R) injury results in decreased glomerular filtration and renal blood flow (RBF) and increased urine output, characterized by natriuresis and impaired concentrating ability. We studied unilateral I/R in rats to assess renal handling of nitric oxide (NO). Prior to I/ R, we measured urine flow rate (V), inulin clearance (C[IN]), para-aminohippuric acid clearance (C[PAH]), NO clearance (C[NOx] determined from metabolites NO2 and NO3), tubular transport of NOx (T[NOx], filtered load +/- urinary excretion), urine sodium and potassium excretion (U[Na]V, U[K]V), fractional excretion of sodium (FENa), and fractional excretion of NOx (FENOx) in each kidney. The left renal artery was then ligated for 30 min, followed by 30 min of reperfusion, and all measurements were repeated. C(IN) and C(PAH) were decreased in I/R kidneys compared with the contralateral kidney or pre-ischemia controls. V, FENa, and U(K)V were all significantly increased in I/R kidneys. Plasma NOx concentration was lower after injury in all animals (23.3 +/- 2.8 post injury vs. 30.4 +/- 7.7 microM pre injury, P < 0.05). C(NOx) was significantly higher in I/R kidneys (0.14 +/- 0.05 ml/min per g kidney weight) than in pre-injury kidneys (0.03 +/- 0.02 right, 0.04 +/- 0.30 left) or the contralateral controls (0.04 +/- 0.02) (P < 0.05 for all three controls). T(NOx) showed net tubular reabsorption of NOx in all kidneys (11 +/- 6 in post-ischemic left kidneys vs. 25 +/- 20 in left pre-ischemia, 33 +/- 13 in right pre-ischemia, and 21 +/- 4 right post-ischemia, nM/min per g kidney weight, P = NS). FENOx was higher in injured kidneys (28% +/- 18) than in pre-injury (3% +/- 0.6, 5% +/- 3) or contralateral controls (6% +/- 3) (P < 0.05 for all three controls). Renal NOx excretion and clearance are increased despite decreased plasma levels of NO metabolites after I/R injury. This increased excretion is not dependent on RBF or glomerular filtration, but may be related to impaired tubular reabsorption of NOx combined with increased intra-renal NO production.
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PMID:Nitric oxide metabolism following unilateral renal ischemia/reperfusion injury in rats. 950 63

Intestinal mucosal injury of various degrees occurs in many clinical situations and is initially evidenced by altered mucosal permeability. The latter may be assessed in animal models by determination of plasma-to-intestinal lumen clearance of specific molecules, usually chromated 51Cr EDTA. The purpose of this study was to evaluate the usage of para-aminohippurate (PHA) as a substitute for the commonly used radioactive material, i.e., 51Cr-EDTA, in the evaluation of intestinal mucosal injury. An isolated loop of ileum was created in rats and constantly perfused with warmed normal saline. Both renal pedicles were ligated. Either 51Cr-EDTA (18.5 Bq/kg) or PAH (58 mg/kg) was injected i.v. Fifteen-minute intestinal ischemia was produced by clamping the superior mesenteric artery immediately after the end of an equilibration period. The perfusate was collected for 10 min prior to the initiation of intestinal ischemia, during the last 10 min of ischemia, and during the following three 10-min periods of reperfusion. Blood samples were collected at the end of each collection period for the determination of either PAH or 51Cr-EDTA concentrations and the calculation of either PHA or 51Cr-EDTA plasma-to-lumen clearances. PAH and 51Cr-EDTA plasma-to-lumen clearances followed the same pattern in all five assessed periods with no statistical difference between the two. PAH plasma-to-lumen clearance is a feasible, reliable, and inexpensive method for the evaluation of ischemia/reperfusion injury to the intestinal mucosa. It can safely replace the commonly used method in animal models that utilizes radioactive materials such as 51Cr-EDTA.
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PMID:Plasma-to-lumen clearance of para-aminohippurate can replace 51Cr EDTA clearance in the evaluation of intestinal mucosal injury. 956 20

United Therapeutics Corp (UTC) is developing treprostinil sodium (Remodulin, UT-15), a stable structural analog of prostacyclin, for the potential treatment of primary pulmonary (arterial) hypertension (PAH), peripheral vascular disease (PVD) and other cardiovascular conditions [327593], including critical limb ischemia (CLI) [412483]. In August 2000, UTC submitted the initial, non-clinical sections of an NDA for the treatment of pulmonary hypertension [378906]. Treprostinil, which had previously been designated as an Orphan Drug, was also awarded Priority Review status by the US FDA in October 2000 [385864], [386271]. In December 2000, UTC agreed with the FDA that the NDA for treprostinil did not need to be presented to the Cardiovascular and Renal Drugs Advisory Committee, which was expected to allow UTC and the FDA to work towards the 6-month Priority Review timeline [393888]. On August 9, 2001, the advisory committee recommended approval of treprostinil and UTC refiled the NDA on the same day [418682]. In February 2002, the FDA issued an approvable letter for treprostinil injection for the treatment of PAH. The FDA proposed drug labeling for PAH consistent with the treatment of both primary and secondary pulmonary hypertension in patients with New York Heart Association (NYHA) Class II-IV symptoms. The approvable letter also stated that the FDA intended to approve treprostinil with a requirement that UTC subsequently conduct a post-marketing controlled clinical trial to verify and further describe the drug's clinical benefit [439278]. In February 2001, UTC submitted a marketing authorization application (MAA) in France for approval of treprostinil for the treatment of PAH. Upon approval of the MAA, UTC planned to file for Mutual Recognition in other European countries and was also preparing similar submissions to non-European countries [391986], [397958]. By early 2001, phase II trials of treprostinil for the treatment of CLI were underway [412483]. In March 2001, the company was planning a phase III pivotal study in late-stage PVD by the end of 2001 [424180]. In April 2000, UTC was issued US-06054486 for the method of treating PVD with treprostinil [364130]. In February 2000, UTC entered into an agreement with Paladin Labs for the exclusive Canadian distribution of treprostinil for the remainder of clinical trials and after regulatory approvals [357302]. In November 2000, UTC and Antigen Pharmaceuticals entered into a strategic alliance for the distribution of treprostinil in the UK and Ireland [390157]. In November 2000, Deutsche Banc Alex Brown predicted a sales potential of US $250 million to US $350 million [418736]. In August 2001, Merril Lynch predicted sales of US $10 million to $20 million in 2002 [420652].
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PMID:Treprostinil sodium Pharmacia. 1209 Jul 28


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