| | Is ischemic preconditioning of the kidney clinically relevant?☆☆☆★Accepted 19 July 2002. Abstract Background. Renal ischemic preconditioning (IPC) is a phenomenon whereby a brief period of ischemia and reperfusion (I/R) provides tolerance to subsequent periods of ischemia. IPC has been demonstrated to protect rodent kidneys during I/R. The applicability to large mammals, including human beings, is unclear. The objective of this study was to determine if renal IPC has a beneficial effect in a large animal model of warm I/R and hypothermic preservation injury, which occurs with renal allografting. Methods. Renal ischemia (45 minutes) and reperfusion was studied in untreated dogs and in dogs receiving IPC (10-minute/10-minute I/R). IPC was administered immediately before I/R (early IPC) or 24 hours before I/R (delayed IPC). In another group of dogs, pharmacologically induced IPC was attempted with local intra-arterial administration of dipyridamole (2.4 mg/kg/min) to increase local adenosine concentrations. Finally, IPC was induced in kidneys before harvest, cold stored for 24 hours in University of Wisconsin flush solution, and subsequently reperfused for 4 hours in allogeneic recipients. Renal functional parameters, including vascular resistance, glomerular filtration rate, urine production, oxygen consumption, and proximal tubular fluid reabsorption, were monitored during the reperfusion period and were compared with the control ischemic group. Results. Renal function significantly declined during I/R, relative to the nonischemic contralateral kidney but was not different with any form of IPC, relative to the ischemic control group not treated with IPC. IPC pretreatment also did not affect the preservation injury observed in cold-stored kidneys reperfused after transplantation. Conclusions. It is concluded that IPC has no significantly measurable effects in warm or hypothermic renal I/R injury in large animals. The clinical usefulness of IPC in human renal ischemic conditions remains uncertain. (Surgery 2003;133:81-90).
The phenomenon of ischemic preconditioning (IPC) was described as increased tolerance to prolonged ischemia achieved by pre-exposing the organ to 1 or more cycles of brief ischemia and reperfusion (I/R). Since the first discovery by Murry in 1986,1 who showed decreased infarction zone in ischemic canine hearts with preconditioning, the phenomenon has garnered great interest in surgical research. Similar observations of salutary preconditioning effects were made in other species including rodents,2 rabbits,3 and pigs,4 and preconditioning responses are strongly suggested in human beings.5 These positive effects of IPC on organ and tissue function have subsequently been described idiomatically as IPC. IPC was also detected in extracardiac organs and tissues such as liver,6 brain,7 intestine,8 and skeletal muscles.9 If IPC also occurs in the kidney, then the phenomenon may be applied in the field of vascular and transplantation operation.
Ischemia associated with cadaveric renal allotransplantation results in significant delayed graft function and remains problematic. Ischemia-associated renal failure is also a common complication after repair of a ruptured abdominal aortic aneurysm and has been found as an independent risk factor for hospital death.10 Mortality is as high as 46% after this surgical procedure and has not improved in more than 20 years according to the National Hospital Discharge Survey. Because the development of postoperative renal insufficiency may increase mortality to 75%,11 every effort should be made to avoid this complication. The possible use of IPC in these clinical settings may be an attractive means of obviating postischemic renal acute tubular necrosis (ATN) and delayed graft function (DGF).
Laboratory investigations using renal IPC have produced conflicting results. A renal IPC effect is observed in rodent13, 14 and cell models15 but not in pigs.16 Because large animals such as pigs and dogs are often regarded as better human surgical models compared with rodents, controversy exists regarding IPC of the kidney and its role in human renal operation. Therefore, the aim of this study was to determine whether IPC produces functional efficacy in a large animal model that may more closely paradigm human beings.
Methods  Animals All animal experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals (National Institutes of Health publication No. 86-36, revised 1985). A total of 38 adult beagle dogs were used for this study. The dogs weighed between 8.6 and 14.2 kg and were of both genders. Two models were used to test the effects of IPC in warm renal I/R injury and hypothermic organ preservation-reperfusion injury. The warm model consisted of the following groups: control (n = 6), ischemia (n = 6), ischemia + acute IPC (n = 6), ischemia + delayed IPC (n = 6), and ischemia + dipyridamole (n = 6). The organ preservation model consisted of 2 groups: control (n = 4) and IPC (n = 4). The numbers of animals chosen for each group in each model was determined by statistical power analysis on the basis of previously determined variances for similar experiments. The dipyridamole group (n = 6) reports only 4 animals because 2 were excluded because of differing dosages of dipyridamole. In situ warm I/R model Dogs were anesthetized with 250 mg of thiopental sodium intravenously and ventilated with 1.5% halothane and a fraction of inspired oxygen of 0.3 using an anesthesia ventilator (SAV 2500, SurgiVet, Waukesha, Wis) adjusted to maintain the arterial pCO2 between 38 and 42 mm Hg. Animals received a 50-mL bolus of an 8 mmol/L lithium chloride solution followed by a constant infusion at 20 to 30 mL/h. Lactated Ringer's solution was also given as a 200-mL bolus followed by a continuous infusion at 20 to 25 mL/kg/h. A midline laparotomy was performed and the right iliac artery was cannulated for constant invasive blood pressure measurements. Both ureters were cannulated and the kidneys were mobilized to avoid collateral blood supply. The renal vessels were exposed and transit time ultrasonic blood flow probes (4 to 6) (Transonic Systems, Ithaca, NY) were placed on both renal arteries. The flow probes were connected to a flow meter for continuous measurement of renal blood flow (Model T201, Transonic Systems). A temperature probe was placed into the abdominal cavity and the incision was temporarily sutured to avoid loss of fluid and temperature. The dogs were allowed to return to a steady state after manipulation, manifested as normal body temperature, mean arterial pressure exceeding 80 mm Hg, and stable renal flow and urine production. This recovery usually required 30 to 40 minutes. Then, urine was collected for 30 minutes, blood was sampled for serum creatinine, and blood pressure and renal blood flows were recorded every 15 minutes for each kidney separately. After obtaining these baseline measurements, the pedicle of one randomly selected kidney was cross-clamped with vascular clamps for 45 minutes. The contralateral kidney served as a nonischemic internal paired control. After 45 minutes of total ischemia at 37°C, the kidneys were allowed to reperfuse under full aortic pressure for 4 hours with the abdomen closed. Renal blood flow and mean systemic arterial blood pressure were recorded and both blood and urine were collected at 0.5, 1, 2, 3, and 4 hours postreperfusion. Glomerular filtration rate (GFR) and the tubular handling of lithium were calculated for both kidneys. At the end of the experiment both kidneys were removed and weighed. Four experimental groups, as follows, were studied and the protocols are illustrated in Fig 1.
I/R group (n = 6) Animals were prepared precisely as described above. Early preconditioned group (n = 6) After recovery to steady state and 30 minutes of baseline measurements and urine collection, the abdomen was reopened and one of the kidneys was preconditioned with 10 minutes of total ischemia and 10 minutes of reperfusion. This protocol was chosen on the basis of previous experience with preconditioning of other canine tissues. Also, multiple cycles of renal preconditioning common to most rodent studies13, 20, 23 were determined to be deleterious to the dog kidney. Immediately after the preconditioning protocol was completed, the pretreated kidney was exposed to 45 minutes of index ischemia and 4 hours of reperfusion. Delayed preconditioned group (n = 6) The day before the experiment, laparotomy was performed under general anesthesia and aseptic conditions as described; one kidney was exposed to preconditioning with 10 minutes of ischemia and reperfused. The abdominal cavity was closed with sutures in the standard manner and the dog was allowed to recover from the operation with free access to food and water. Analgesia was achieved with 4 mg of morphine sulfate intravenously during the procedure. Twenty-four hours later the animal was anesthetized again and manipulated as in the I/R group. Dipyridamole group (n = 4) After obtaining baseline measurements, 2.4 mg/kg/min of dipyridamole was infused into the renal artery for 10 minutes. Subsequently, the dipyridamole preconditioned kidney was subjected to ischemia for 45 minutes and reperfused for 4 hours as described. In preliminary experiments, a dose of 0.24 mg/kg/min was used, which previously demonstrated increases of endogenous renal adenosine.17 However, we were not able to see either the systemic effect of adenosine accumulation or any protective effect against ischemic injury, so the dose was increased 10-fold. This dose given locally into the renal artery was the greatest dose that did not produce significant changes in systemic arterial blood pressure. Dipyridamole was dissolved in acidified saline solution (approximately pH 3.5). Finally, the contralateral kidneys that did not experience ischemia served as the paired internal control for which renal flow, urine production, GFR, and lithium reabsorption was calculated. Allotransplantation model Male beagle dogs were anesthetized as described. Left nephrectomy was performed after hydration with a bolus of 300 mL of lactated Ringer's solution followed by infusion at approximately 20 mL/kg/h and administration of 1 g/kg of mannitol. The removed kidney was flushed with 100 mL of cold (+4°C) University of Wisconsin (UW) solution and cold stored in UW for 24 hours. The recipient was another male animal given a 50-mL bolus of 8 mmol/L lithium chloride solution followed by an infusion of 20 to 30 mL/h with lactated Ringer's solution and mannitol as previously described. The left iliac artery was cannulated for continuous invasive blood pressure measurement. The renal vein of the allograft was anastomosed end-to-side to the right common iliac vein above the confluence of the external and internal iliac veins. A catheter was introduced through the internal iliac vein into the renal vein for blood sampling. The renal artery was sutured end-to-end with the common iliac artery. The ureter was cannulated and a flow probe was placed on the renal artery. Immediately after revascularization of the cold-stored allograft, bilateral nephrectomy of the native kidneys was performed, the abdomen was closed, and the kidney was allowed to reperfuse for 4 hours. Renal blood flow, arterial pressure, and urine production were recorded while urine and blood samples were taken at 0.5, 1, 2, 3, and 4 hours. At the end of the experiment, the kidney was removed, weighed, and GFR, lithium clearance, and oxygen consumption were calculated. Two groups of animals in this series were studied; a nontreated control group (n = 6) and a preconditioned transplant group (n = 4). In the preconditioned transplant group, the kidney was preconditioned with 2 cycles of 8 minutes of ischemia and 5 minutes of reperfusion each before organ retrieval. Longer ischemia times during preconditioning or greater numbers of cycles were found to be deleterious in the dog model. Furthermore, the preconditioning protocol used for this experiment was found to be optimal in preliminary experiments using isolated canine proximal tubules that were cold stored in UW with subsequent reoxygenation at 37°C. Both the renal artery and vein were simultaneously cross-clamped to induce preconditioning ischemia. Immediately after the preconditioning protocol was completed, the kidney was removed, flushed with cold UW solution, bagged, and stored on ice until transplantation. Isolated renal tubules Primary renal proximal tubules were isolated from freshly removed dog kidneys as previously described.18, 19 After isolation, tubules were gently pelleted by low-speed centrifugation and subjected to 60 minutes of warm ischemia by placing them into media purged of oxygen using 95% nitrogen and 5% CO2. After ischemia, the cells were placed into cold UW solution for 24 hours in a refrigerated water bath oscillating at 1 Hz under an air atmosphere. After cold storage, the cells were rewarmed in Weinberg's A+ medium18 for 1 hour under an atmosphere of 95% oxygen and 5% CO2 to simulate reperfusion. Cell viability (total lactate dehydrogenase release) was then determined. This was the ischemic positive control group. In the negative control group, tubules were freshly isolated and viability was assessed. Two test groups used IPC consisting of 1 or 4 cycles of 8 minutes of ischemia and 5 minutes of reoxygenation20 before induction of warm ischemia, cold storage, and reperfusion. Ischemia and reoxygenation used during preconditioning cycles was accomplished by placing the tubules into deoxygenated and oxygenated buffer, respectively. Analysis and calculations Creatinine in serum and urine (urine was diluted 1:9 vol/vol with water) was measured on a Kodak EktachemDT60 analyzer (Kodak; Ortho-Clinical Diagnostics, Rochester, NY). GFR was estimated as the renal clearance of creatinine. The partial pressure of oxygen and CO2 in the blood samples and hemoglobin saturation with oxygen were measured at 37°C using a Rapidlab 348 pH/blood gas analyzer (Bayer Diagnostics, East Walpole, Mass). Hemoglobin concentrations were determined with a calorimetric Drabkin's method21 using a UV-160 Shimadzu Spectrophotometer (Kyoto, Japan). Oxygen consumption of the transplanted and contralateral kidneys was calculated from Fick's equation assuming Hüfner's number for canine hemoglobin to be 1.34 mL O2 × mg−1. Lithium concentration in the sera and urine samples was measured with atomic absorption spectrophotometer (AA-6200, Shimadzu). Samples were diluted 1:9 vol/vol with deionized water. Proximal tubular reabsorption of isotonic fluid (FRLi) was calculated from GFR and lithium clearance as a percent of filtered load such that:
FRLi = (GFR − ClLi) × GFR −1 × 100 where ClLi is lithium clearance. Statistical analysis was performed using analysis of variance and Bonferroni multiple comparison posttest for parametric data and the Kruskal-Wallis test with Dunn multiple comparison test for nonparametric data (vascular resistance and percentages). All data are expressed as the mean ± SD. P values < .05 were considered statistically significant. Results In situ I/R Vascular resistance is shown in Fig 2, upper panel, and was decreased in all of the pretreated groups as compared with the I/R group immediately after reperfusion, although these changes were not significant.
The GFRs ( Fig 2, lower panel) were all depressed in the ischemia groups compared with the native nonischemic controls but the GFR in the ischemic groups was not affected by acute or delayed IPC or by attempts at chemical preconditioning with dipyridamole pretreatment. Fig 3, upper panel, illustrates urine production by untreated and preconditioned kidneys expressed as a percentage of the native kidney to control for changes in hydration of individual animals.
Urine production decreased after ischemia and early reperfusion but tended to increase throughout the 4-hour reperfusion period. Urine production rates that increased steadily above the internal controls (100%) in the ischemia and dipyridamole groups may represent high output renal failure because GFR values for these animals remained depressed ( Fig 2). Curiously, kidneys subjected to delayed preconditioning displayed the lowest urine production rates during the reperfusion period but the differences were not statistically significant. Finally, the fractional reabsorption of FR Li from the proximal tubules was determined in all 5 groups of kidneys during the reperfusion period ( Fig 3, lower panel). No statistically significant differences in any of the groups were observed in this study. It is of interest that the proximal tubular fluid reabsorption rate was not demonstrably depressed in the control untreated ischemic kidneys when compared with the nonischemic kidneys. Unlike GFR ( Fig 2), this indicator of renal function apparently is not sensitive to I/R injury as used in this particular model. Allotransplant Similar to the warm I/R model, no major functional differences between preconditioned and nonpreconditioned groups were detected in the cold preservation model. Both groups had identical vascular resistance patterns (Fig 4, upper panel).
Oxygen consumption was similar after 1 and 2 hours of reperfusion in the control and preconditioned groups ( Fig 4, lower panel). However, at the beginning of reperfusion (30 minutes), oxygen consumption was significantly improved ( P < .01) in the preconditioned group, relative to the control group. This was significant once more during the last 2 hours of reperfusion with oxygen consumption being higher ( P < .01) in the preconditioned group. Because blood flow was similar in both groups, the increased oxygen consumption in the preconditioned group was metabolic in origin and not flow-dependent. GFRs and urine production in the 2 groups were also not different after 4 hours of reperfusion (Fig 5).
Fractional reabsorption of FR Li by the proximal tubules tended to be improved in the preconditioned group, although the differences were not significant. Four hours after reperfusion, proximal tubular fluid reabsorption rate was 91.6 ± 5.9% of total filtered load in control unmodified cold-stored kidneys and 94.6 ± 3.7% in the preconditioned group. Isolated renal proximal tubules The effects of IPC on isolated dog proximal renal tubules is shown in Fig 6.
Ischemic injury induced by a period of warm ischemia and 20 hours of cold preservation with UW flush followed by rewarming under an oxygen atmosphere was used to simulate clinical organ preservation injury in the isolated tubule preparations. This protocol produced significant loss of cell viability as indexed by total lactate dehydrogenase release (7% release in fresh uninjured tubules compared with 40% release in preserved tubules). Either 1 or 4 cycles of IPC administered before the induction of the preservation injury protocol significantly attenuated the loss of cell viability observed after reperfusion (aerobic rewarming). Thus, IPC is effective in mitigating injury in isolated dog renal tubules subjected to hypothermic I/R, but no effect is observed in an analogous whole organ preparation ( Fig. 4, Fig. 5). Discussion Preconditioning induced by either brief periods of I/R or by chemical induction with dipyridamole had no effect on any functional parameter measured in a large animal model of warm renal I/R injury. Cold I/R injury, typically encountered with clinical renal allografting, was also unaffected by IPC in a dog model but IPC was observed in the isolated dog renal tubules. Finally, neither immediate nor delayed IPC effects could be observed in this study. The occurrence of IPC differs between both tissues within the same species and in the same tissue between species. IPC has been studied in large and small mammals and in various organs and tissues. Small mammals generally have included rats, mice, and rabbits, whereas large mammals include dogs, pigs, and, in some cases, human beings. Myocardial IPC irrefutably occurs in both large and small mammals and was first documented in a dog model of myocardial I/R.1 Preconditioning attempts in other organs, however, are more controversial. Renal IPC has been identified to occur in whole kidney preparations in rats13, 20 and mice.14 Furthermore, renal cell cultures derived from many species including human beings, rodents, and pigs strongly demonstrate IPC.15, 22 In fact, this study has demonstrated IPC in primary canine renal proximal tubule preparations (Fig 6) but we were unable to document the phenomenon in the whole dog kidney, illustrating that even differences between tissue and whole organ preparations exist. To the best of our knowledge, only 2 studies have attempted to identify renal IPC in large mammals: this current article using dog kidneys and one in porcine kidneys.16 Both studies failed to demonstrate renal preconditioning in these 2 large animal species, which differ strongly with reports in small animal species.13, 14, 20, 23, 24, 25 Furthermore, this study attempted to identify renal IPC using both immediate and delayed protocols, because preconditioning is generally believed to exist under both conditions using different mechanisms.14, 26, 27 Similar to acute renal preconditioning, delayed renal preconditioning in dogs was also without effect. Therefore, these results and others suggest some canine organs undergo IPC (heart), whereas others do not (kidney). On the other hand, most organs and tissues in some small animal species such as the rat are amenable to IPC. Answers to these questions concerning species differences with IPC in the kidney and the seemingly universal demonstration of IPC in cardiac tissue across species may derive from the mechanisms of IPC. The mechanisms of IPC seem to include a few well-described signal transduction pathways. These generally include, but are not limited to, adenosine receptor mediated activation of adenosine triphosphate (ATP)-gated potassium (K+) channels,9, 28 nitric oxide synthesis,8, 23, 29 free radical generation,29, 30, 31 and the up-regulation of molecular chaperones.7, 32 If one were to explore the reasons for differences in observing IPC between various tissues within one species or in any given tissue or organ type between species, then it seems logical to determine if these tissues and species possess the known IPC mechanisms. Generally, muscle tissue from all species seems to experience IPC, whereas tissues of nonmuscle ontological origin such as kidney or endocrine tissue rarely demonstrate IPC.22 Furthermore, embryonic muscle tissues often do not display IPC but will switch to an IPC phenotype with maturation beyond embryonic states of development, suggesting a genetic activation of specific IPC-dependent proteins.22 Tissue from brain, skeletal muscle, and cardiac muscle strongly express messenger RNA for some ATP-sensitive potassium channel proteins, whereas lung and kidney weakly express these proteins.33 Because ATP-sensitive K+ channels seem to be necessary for the development of IPC, tissues such as kidney that seem to express less of these proteins may be refractory to the development of IPC. In addition to ATP-gated K+ channels, the binding affinity of adenosine agonists to their respective receptors is higher in rat tissues compared with other species, including humans.34 Because IPC may require the activation of K+ATP channels by adenosine receptors, then these differences in signaling pathways between tissues and species may partially account for the lack of observance of IPC in dog kidneys in this study and perhaps pig kidneys in a previous study.16 Renal IPC can be mimicked with the administration of various adenosine receptor agonists in rats20 and ischemia results in the local release of adenosine into the interstitial space where it becomes available for receptor binding. It may be argued that the salutary effects of IPC (local adenosine release) are offset by the pejorative effects of the ischemia. Therefore, the effects of chemical preconditioning using dipyridamole were tested to bypass the possible negative effects of the ischemia. Dipyridamole at the dosage used has been shown to significantly increase extracellular adenosine concentrations in canine kidneys17 by preventing cellular adenosine reuptake, but this maneuver was not protective (Fig. 2, Fig. 3). Therefore, increased local renal adenosine concentrations may not activate preconditioning signal transduction mechanisms in the dog. The lack of protection of IPC in the warm renal I/R model in the dog was similar in a clinically relevant renal transplant preservation ischemia model using cold storage. Presuming that the effects of reperfusion injury after warm and cold renal ischemia are similar, then it may not be surprising to find the shortcomings of IPC to be similar in both models. In contrast, IPC of donor lungs before removal and storage in Eurocollins solution significantly improves posttransplant lung function in a dog model.35 Perhaps differences exist between dog lung and kidney regarding preconditioning with ischemia or maybe the differences in the flush solutions (Collins vs UW solution) is important. In fact, UW solution contains high adenosine concentrations (5 mmol/L) as compared with Eurocollins (0 mmol/L) and UW cold storage provides superior protection of organs from cold I/R injury compared with Eurocollins solution.36 Therefore, it may be argued that adenosine in the UW solution may already activate preconditioning mechanisms in cold-stored kidneys in this study. The adenosine release with IPC before cold storage may be relatively insignificant compared with the huge concentration of adenosine present in the UW flush (5 mmol/L). Thus, UW flush may, in effect, precondition kidneys for the ischemia encountered during cold storage, an effect not observable in Eurocollins solution, which is adenosine deficient. Attempts to reverse some of the beneficial effects of UW flush preservation in the kidney with selective adenosine receptor antagonists or demonstrating an IPC effect in dog kidneys preserved with adenosine deficient Eurocollins solution would address this hypothesis. This study concludes that salutary functional effects of IPC are not demonstrable in dog kidneys subjected to either normothermic or hypothermic ischemia and acute reperfusion. However, possible IPC effects cannot be ruled out in longer-term reperfusion where further preservation injury occurs. Considerable differences in renal IPC induction exist between large and small animal species and within tissues of the same species. Differences in IPC have been even documented between proximal tubule preparations and the kidneys deriving those same cells. Thus, the clinical use of renal IPC as currently practiced in animals seems doubtful in human beings. References 1.
1
Murry CE, Jennings RB, Reimer KA.
Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium.
Circulation. 1986;74:1124–1136. MEDLINE 2.
2
Liu Y, Downey JM.
Ischemic preconditioning protects against infarction in rat heart.
Am J Physiol. 1992;263:H1107–H1112. MEDLINE 3.
3
Iwamoto T, Miura T, Adachi T, Noto T, Ogawa T, Tsuchida A, et al.
Myocardial infarct size-limiting effect of ischemic preconditioning was not attenuated by oxygen free-radical scavengers in the rabbit.
Circulation. 1991;83:1015–1022. MEDLINE 4.
4
Kida M, Fujiwara H, Ishida M, Kawai C, Ohura M, Miura I, et al.
Ischemic preconditioning preserves creatine phosphate and intracellular pH.
Circulation. 1991;84:2495–2503. MEDLINE 5.
5
Wu ZK, Pehkonen E, Laurikka J, Kaukinen L, Honkonen EL, Kuakinen S, et al.
Protective effect of unstable angina in coronary artery bypass surgery.
Scand Cardiovasc J. 2000;34:486–492. MEDLINE |
CrossRef
6.
6
Kume M, Yamamoto Y, Saad S, Gomi T, Kimoto S, Shimabukuro T, et al.
Ischemic preconditioning of the liver in rats: implications of heat shock protein induction to increase tolerance of ischemia-reperfusion injury.
J Lab Clin Med. 1996;128:251–258. Abstract |
Full-Text PDF (1642 KB)
|
CrossRef
7.
7
Kato H, Liu Y, Kogure K, Kato K.
Induction of 27-kDa heat shock protein following cerebral ischemia in a rat model of ischemic tolerance.
Brain Res. 1994;634:235–244. MEDLINE |
CrossRef
8.
8
Hotter G, Closa D, Prados M, Fernandez-Cruz L, Prats N, Gelpi E, et al.
Intestinal preconditioning is mediated by a transient increase in nitric oxide.
Biochem Biophys Res Commun. 1996;222:27–32.
CrossRef
9.
9
Jerome SN, Akimitsu T, Gute DC, Korthuis RJ.
Ischemic preconditioning attenuates capillary no-reflow induced by prolonged I/R.
Am J Physiol. 1995;268:H2063–H2067. MEDLINE 10.
10
Heller JA, Weinberg A, Arons R, Krishnasastry KV, Lyon RT, Deitch JS, et al.
Two decades of abdominal aortic aneurysm repair: have we made any progress?.
J Vasc Surg. 2000;32:1091–1100. Abstract | Full Text |
Full-Text PDF (93 KB)
|
CrossRef
11.
11
Barratt J, Parajasingam R, Sayers RD, Feehally J.
Outcome of acute renal failure following surgical repair of ruptured abdominal aortic aneurysms.
Eur J Vasc Endovasc Surg. 2000;20:163–168. Abstract |
Full-Text PDF (93 KB)
|
CrossRef
12.
12
Toosy N, McMorris EL, Grace PA, Mathie RT.
Ischaemic preconditioning protects the rat kidney from reperfusion injury.
BJU Int. 1999;84:489–494. MEDLINE |
CrossRef
13.
13
Park KM, Chen A, Bonventre JV.
Prevention of kidney ischemia/reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment.
J Biol Chem. 2001;276:11870–11876. MEDLINE |
CrossRef
14.
14
Turman MA, Bates CM.
Susceptibility of human proximal tubular cells to hypoxia: effect of hypoxic preconditioning and comparison to glomerular cells.
Ren Fail. 1997;19:47–60.
CrossRef
15.
15
Behrends M, Walz MK, Kribben A, Neumann T, Helmchen U, Philipp T, et al.
No protection of the porcine kidney by ischaemic preconditioning.
Exp Physiol. 2000;85:819–827. MEDLINE |
CrossRef
16.
16
Arend LJ, Thompson CI, Spielman WS.
Dipyridamole decreases glomerular filtration in the sodium-depleted dog. Evidence for mediation by intrarenal adenosine.
Circ Res. 1985;56:242–251. MEDLINE 17.
17
Saunder A, Ametani MS, Belzer FO, Southard JH.
Cytoprotective effect of glycine in cold stored canine renal tubules.
Cryobiology. 1993;30:243–249. MEDLINE |
CrossRef
18.
18
Weinberg JM, Davis JA, Abarzua M, Rajan T.
Cytoprotective effects of glycine and glutathione against hypoxic injury to renal tubules.
J Clin Invest. 1987;80:1446–1454. MEDLINE |
CrossRef
19.
19
Lee HT, Emala CW.
Protective effects of renal ischemic preconditioning and adenosine pretreatment: role of A(1) and A(3) receptors.
Am J Physiol Renal Physiol. 2000;278:F380–F387. MEDLINE 20.
20
Drabkin DL, Austin JH.
Spectrophotometric studies II: preparations from washed blood cells; nitric oxide hemoglobin and sulfhemoglobin.
J Biol Chem. 1935;112:51. 21.
21
Liu Y, Gao WD, O'Rourke B, Marban E.
Cell-type specificity of preconditioning in an in vitro model.
Basic Res Cardiol. 1996;91:450–457. MEDLINE |
CrossRef
22.
22
Jefayri MK, Grace PA, Mathie RT.
Attenuation of reperfusion injury by renal ischaemic preconditioning: the role of nitric oxide.
BJU Int. 2000;85:1007–1013. MEDLINE |
CrossRef
23.
23
Cochrane J, Williams BT, Banerjee A, Harken AH, Burke TJ, Cairns SB, et al.
Ischemic preconditioning attenuates functional, metabolic, and morphologic injury from ischemic acute renal failure in the rat.
Ren Fail. 1999;21:135–145.
CrossRef
24.
24
Islam CF, Mathie RT, Dinneen MD, Kiely EA, Peters AM, Grace PA.
Ischaemia-reperfusion injury in the rat kidney: the effect of preconditioning.
Br J Urol. 1997;79:842–847. MEDLINE 25.
25
Pagliaro P, Gattullo D, Rastaldo R, Losano G.
Ischemic preconditioning: from the first to the second window of protection.
Life Sci. 2001;69:1–15. MEDLINE |
CrossRef
26.
26
Mockridge JW, Punn A, Latchman DS, Marber MS, Heads RJ.
PKC-dependent delayed metabolic preconditioning is independent of transient MAPK activation.
Am J Physiol Heart Circ Physiol. 2000;279:H492–H501. MEDLINE 27.
27
Gaudette GR, Krukenkamp IB, Saltman AE, Horimoto H, Levitsky S.
Preconditioning with PKC and the ATP-sensitive potassium channels: a codependent relationship [see comments].
Ann Thorac Surg. 2000;70:602–608. MEDLINE |
CrossRef
28.
28
Nakano A, Liu GS, Heusch G, Downey JM, Cohen MV.
Exogenous nitric oxide can trigger a preconditioned state through a free radical mechanism, but endogenous nitric oxide is not a trigger of classical ischemic preconditioning.
J Mol Cell Cardiol. 2000;32:1159–1167. Abstract |
Full-Text PDF (124 KB)
|
CrossRef
29.
29
Baines CP, Goto M, Downey JM.
Oxygen radicals released during ischemic preconditioning contribute to cardioprotection in the rabbit myocardium.
J Mol Cell Cardiol. 1997;29:207–216. Abstract |
Full-Text PDF (335 KB)
|
CrossRef
30.
30
Das DK, Maulik N, Sato M, Ray PS.
Reactive oxygen species function as second messenger during ischemic preconditioning of heart.
Mol Cell Biochem. 1999;196:59–67. MEDLINE |
CrossRef
31.
31
Tanaka M, Fujiwara H, Yamasaki K, Yokota R, Doyama K, Inada T, et al.
Expression of heat shock protein after ischemic preconditioning in rabbit hearts.
Jpn Circ J. 1998;62:512–516. MEDLINE |
CrossRef
32.
32
Sakura H, Ammala C, Smith PA, Gribble FM, Ashcroft FM.
Cloning and functional expression of the cDNA encoding a novel ATP-sensitive potassium channel subunit expressed in pancreatic beta-cells, brain, heart and skeletal muscle.
FEBS Lett. 1995;377:338–344. Abstract |
Full-Text PDF (627 KB)
|
CrossRef
33.
33
Maemoto T, Finlayson K, Olverman HJ, Akahane A, Horton RW, Butcher SP.
Species differences in brain adenosine A1 receptor pharmacology revealed by use of xanthine and pyrazolopyridine based antagonists.
Br J Pharmacol. 1997;122:1202–1208. MEDLINE |
CrossRef
34.
34
Li G, Chen S, Lou W, Lu E.
Protective effects of ischemic preconditioning on donor lung in canine lung transplantation.
Chest. 1998;113:1356–1359. MEDLINE |
CrossRef
35.
35
Southard JH, Belzer FO.
Organ preservation.
Annu Rev Med. 1995;46:235–247. MEDLINE |
CrossRef
Madison, Wis From the Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine, Madison, Wis ☆ Supported by a grant from the Public Health Service (National Institutes of Health) DK-44254. ☆☆ Reprint requests: Martin J. Mangino, PhD, Department of Surgery, Division of Organ Transplantation, University of Wisconsin Hospital and Clinics, H4/333 Clinical Science Center, 600 Highland Ave, Madison, WI 53792. ★ 0039-6060/2003/$30.00 + 0 PII: S0039-6060(02)21693-1 doi:10.1067/msy.2003.93 © 2003 Published by Elsevier Inc. | |
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