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Results for “Cold Ischemia”

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At least 19 recordsLinked to original sources

PubMed2003

Na+/H+ exchange inhibition with cardioplegia reduces cytosolic [Ca2+] and myocardial damage after cold ischemia.

Cold cardioplegia protects against reperfusion damage. Blocking Na+/H+ exchange may be as protective as cardioplegia by improving the left ventricular pressure (LVP)-[Ca2+] relationship after cold ischemia. In guinea pig isolated hearts subjected to cold ischemia (4 h, 17 degrees C) and reperfusion, the cardioprotective effects of a Krebs-Ringer (KR) solution, a cardioplegia solution, a KR solution containing the Na+/H+ exchange inhibitor eniporide (1 microM), and a cardioplegia solution containing eniporide were compared. Treatments were given before and initially after cold ischemia. Systolic and diastolic [Ca2+] were calculated from indo-1 fluorescence transients recorded at the LV free wall. During ischemia, diastolic [Ca2+] increased in each group but more so in the KR group. Peak systolic and diastolic [Ca2+] on initial reperfusion were highest after KR and smallest after cardioplegia + eniporide. After reperfusion, systolic-diastolic LVP (% of baseline) and infarct size (%), respectively, were KR, 47 +/- 3%, 37 +/- 4%; cardioplegia, 71 +/- 5%*, 20 +/- 2.2%*; KR + eniporide, 73 +/- 5%*, 11 +/- 3%* dagger; and cardioplegia + eniporide 77 +/- 3%*, 10 +/- 1.4%* dagger (*P </= 0.05 vs KR; dagger P </= 0.05 vs cardioplegia). Ca2+ overload was reduced in each treated group, and most in the cardioplegia + eniporide group, and was associated with the improved function. Inhibition of Na+/H+ exchange was as effective as cardioplegia in restoring function and better than cardioplegia in reducing infarct size after hypothermic ischemia. The combination of cardioplegia and Na+/H+ exchange inhibition did not produce additive protective effects but caused a larger decrease in Ca2+ loading.

Animals↗

PubMed1998

[Prevention of ischemia before cold ischemia by pharmcologic donor conditioning--experimental findings].

The loop-diuretic piretanide was used to study the influence of pharmacological donor pretreatment on immediate postischemic function in a pig model of kidney transplantation based on the results of a clinical pilot study [4]. Following laparotomy, both kidneys were flushed via a transaortal catheter with Eurocollins-solution and surgically removed. A cold ischemic period of 1 or 24 h was chosen. After that period, kidneys were reperfused with intraoperatively drawn heparinized blood for one hour. We used a special instrument for hemoperfusion of isolated organs which allows perfusion for several hours under steady-state conditions. Four groups were formed: Control and piretanide, 1 or 24 h cold ischemia. The perfusion of piretanide-treated organs resulted in a lower perfusion-resistance, calculated as pressure/flow-ratio or as pressure/glomerular filtrationratio. The flow in the pretreated group was higher, thus excluding a higher shunt-volume. In parallel, oxygen consumption as a parameter of postischemic function start and creatinine clearance were higher in the piretanide treated groups. The experiments demonstrate a superior postischemic function of pretreated kidneys in comparison to control organs after 1 and 24 hours of cold ischemia in this model.

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PubMed2002

Porcine hepatic phospholipid efflux during reperfusion after cold ischemia.

BACKGROUND: Cold preservation produces hepatic injury that is difficult to assess during early reperfusion. The value of reperfusion plasma choline phospholipid in predicting subsequent organ function is documented in these studies. MATERIALS AND METHODS: Livers of female Yorkshire pigs were prepared for transplantation. After 2 h of cold ischemia the reperfusion plasma was evaluated for choline phospholipid and cholesterol. These values were correlated with bile secretion, hepatic hemodynamics, oxygen uptake, and plasma sorbitol dehydrogenase levels. RESULTS: The isolated porcine liver demonstrates a rapid efflux of choline phospholipids into plasma during early reperfusion after cold preservation. After this initial efflux no subsequent plasma increment occurred. These choline-phospholipid increments were isolated in plasma higher density (d > 1.063) lipoproteins and were not accompanied by equivalent increases in cholesterol. Neither biliary reflux nor lecithin cholesterol acyl transferase abnormalities contributed appreciably to the phospholipid increments in reperfusion plasma. Livers with the largest efflux of choline phospholipids had the most impaired circulatory and bile secretory function at 4 h of reperfusion. CONCLUSION: The immediate increase of choline phospholipids, particularly lysophosphatidylcholine, in reperfusion plasma after cold ischemia provides an index of the injury occurring during this interval and correlates with early organ function.

Animals↗

PubMed1999

Fragility of the electron transport chain and superoxide generation in mitochondria of the liver graft after cold ischemia.

BACKGROUND: After cold ischemia, electrons transferred in the electron transport chain may leak out of the mitochondria in proportion to the deterioration of mitochondrial oxidative phosphorylation. This seems to be one major cause of the lipid peroxidation that occurs mainly in the hepatocytes at reperfusion in liver transplantation. To examine this hypothesis, we investigated superoxide generation and the amount of oxidative phosphorylation in the mitochondria isolated from rat livers after cold preservation. METHODS: Rat liver was preserved in University of Wisconsin solution at 4 degrees C for 24 hr. The mitochondrial fraction was prepared, and the amount of ATP synthesis and superoxide generation was investigated. Superoxide generation in the electron transport chain of submitochondrial particles was also measured by a chemiluminescence recorder. RESULTS: The amount of ATP synthesis was significantly decreased after 12 hr of cold preservation. In the whole mitochondria, superoxide production in the presence of succinate was approximately 1/2000 to 1/3000 less than that observed in the submitochondrial particles at any determination point, and superoxide production was not affected by cold preservation. In the presence of antimycin A, superoxide production in the mitochondria after 18 hr of preservation increased significantly. CONCLUSION: These results indicate that the electron transfer in the complex III of the mitochondrial membrane becomes leaky after long periods of cold ischemia, but that leakage of superoxide anion did not increase, although the mitochondrial respiratory phosphorylation was deteriorated. We conclude that superoxide through the mitochondrial membrane cannot cause lipid peroxidation in hepatocytes at reperfusion even after a long period of cold ischemia.

Adenosine Triphosphate↗

PubMed2002

Different patterns of renal cell killing after warm and cold ischemia.

Kidneys preserved for transplantation surgery sustain injuries caused by cold ischemia during storage. Additionally, kidneys harvested from non-heart-beating donors encounter the stress of warm ischemia. The aim of this study was to determine the specific cell types losing viability after warm and cold ischemia. In warm ischemia studies, the pedicles of left kidneys of Lewis rats were cross-clamped for up to 90 min. In cold ischemia studies, kidneys were flushed with cold University of Wisconsin solution and stored up to 48h at 0-1 degrees C. After warm or cold ischemia, kidneys were perfused via the renal arteries with Krebs-Henseleit bicarbonate (KHB) buffer at 37 degrees C, followed by trypan blue to label the nuclei of nonviable cells. Warm ischemia for 90 min caused renal failure and led to injury of proximal tubular cells, e.g., loss of brush borders, cast formation and trypan blue labeling. Cold ischemia for 48 h also caused renal failure but, unlike warm ischemia, caused trypan blue labeling of glomerular podocytes and peritubular endothelial cells. In warm ischemia-induced injury, electron microscopy showed shedding of microvilli and marked swelling of proximal tubular cells, microvilli and mitochondria. In cold ischemia-induced injury, podocytes were blebbed and swollen, and their pedicels were detached from the basement membrane, but disruption in proximal tubules was milder. In conclusion, warm ischemia triggers injury primarily to proximal tubular cells, whereas cold ischemia damages glomerular podocytes and peritubular endothelial cells in addition to proximal tubules.

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PubMed2001

Addition of ATP and MgCl2 to the preservation solution attenuates lung reperfusion injury following cold ischemia.

BACKGROUND: In lung transplantation, reperfusion injury following cold ischemia is one of the crucial problems for recipients. OBJECTIVE: We evaluated the protective effect of adding a combination of ATP and MgCl2 to the preservation solution against lung reperfusion injury following cold ischemia. METHODS: Using an isolated rat lung perfusion model with fresh rat blood as the perfusate, the rats were divided into five groups (n = 6). In the fresh group, the study lungs were flushed with phosphate-buffered saline (PBS), then immediately reperfused for 120 min. In the control group, the study lungs were flushed with PBS, then cold ischemia was induced for 9 h (4 degrees C), after which reperfusion was performed. In the other three groups, the protocols were the same as for the control group except that ATP and/or MgCl2 were added to the PBS: ATP group (100 microM ATP), MgCl2 group (100 microM MgCl2) and ATP + MgCl2 group (100 microM ATP + 100 microM MgCl2). RESULTS: In the ATP + MgCl2 group, the intrapulmonary shunt fraction, peak airway pressure and wet to dry lung weight ratio were significantly lower than those in the control group. No improvement was observed in the ATP or MgCl2 groups. Histological examination supported these physiological results. In all groups, flush time and lipid peroxide levels in the lungs after cold ischemia did not show any significant differences. CONCLUSION: The addition of ATP and MgCl2 to the preservation solution attenuated reperfusion injury following cold ischemia in rat lungs.

Adenosine Triphosphate↗

PubMed1998

Role of glutathione in hepatic bile formation during reperfusion after cold ischemia of the rat liver.

BACKGROUND/AIMS: Liver reperfusion following cold ischemia is frequently associated with diminished bile flow in patients undergoing liver transplantation. Glutathione is a major determinant of bile-acid independent bile flow, and the effects of cold ischemia on biliary glutathione excretion are unknown. METHODS: We examined the effects of cold ischemia (University of Wisconsin solution (4 degrees C), 24 h) with subsequent reperfusion (100 min) on biliary glutathione excretion in a recirculating system. Since glutathione might represent an important antioxidant within the biliary tract and oxidative stress in the biliary tract during reperfusion could contribute to the pathogenesis of bile duct injury after liver transplantation, we also assessed bile duct morphology in reperfused livers of mutant TR- -rats, in whom biliary excretion of glutathione is already impaired. RESULTS: Hepatic bile formation was diminished in reperfused Wistar rat livers after cold ischemia. Biliary glutathione concentrations and output were significantly decreased and correlated with postischemic changes in bile secretion. An increased biliary oxidized glutathione/glutathione ratio, indicating oxidative stress, was detected only immediately after the onset of reperfusion. Basal bile flow rates in TR- -rat livers which were already markedly reduced in control-perfused livers, decreased further during the early but not the later reperfusion period. Reperfusion of both Wistar and TR- -rat livers was not associated with electron microscopic evidence of bile duct damage. CONCLUSIONS: We conclude that impaired biliary excretion of glutathione contributes to decreased bile flow after cold ischemia. The absence of biliary glutathione does not appear to promote ultrastructural evidence of bile duct injury during reperfusion in the isolated perfused rat liver.

Adenosine↗

PubMed2002

Cold ischemia induces isograft arteriopathy, but does not augment allograft arteriopathy in non-immunosuppressed hosts.

Prolonged cold ischemia has been suggested as a factor that will exacerbate later graft arterial disease (GAD), a major limiting factor for long-term transplant survival. We therefore examined the effects of cold ischemia on GAD as well as adhesion molecule and cytokine expression in murine cardiac grafts. Mild GAD developed in isografts undergoing 4-hour cold ischemia. Relative to control isografts, cold ischemia induced transiently enhanced endothelial expression of intercellular adhesion molecule-1 (ICAM-1) at 4 hours post-transplant. There was also transiently-augmented gene expression of interleukin (IL)-1beta, IL-6, and transforming growth factor-beta in these cold-ischemic isografts. By 3 days post-transplantation, however, there were no longer any differences between control and cold ischemic isografts. Cold ischemia did not significantly affect the final grade of either parenchymal rejection or GAD in long-term (4 to 12 weeks) major histocompatibility complex (MHC) I- or MHC II-mismatched allografts molecules transplanted without immunosuppression. At early time points after cold ischemia (4 to 24 hours), allografts mismatched for MHC I and/or MHC II showed enhanced expression of ICAM-1 and cytokines comparable to that seen in isografts. By day 7 post-transplant, both control and cold ischemia allografts showed comparable expression of cytokines and adhesion molecules. Although prolonged cold ischemia can initiate mild GAD in isografts by transiently enhancing antigen non-specific inflammatory responses, it does not significantly augment subsequent alloresponses.

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PubMed2000

NFkappaB expression during cold ischemia correlates with postreperfusion graft function.

In liver transplantation, activation of NFkappaB occurs upon reperfusion, yet few data exist regarding NFkappaB activation during cold ischemia. We hypothesized that activation of NFkappaB may initially occur during cold ischemia, prior to reperfusion, and serve as an important determinant of postreperfusion function. To test this hypothesis, serial biopsies during porcine liver harvest were obtained immediately upon laparotomy, upon completion of dissection, after 45 and 120 min of cold ischemia, and 60 and 180 min after reperfusion. Nuclear extracts were isolated for Western blot analysis of NFkappaB. Hepatic function was assessed through bile output and sorbitol dehydrogenase (SDH) activity. NFkappaB expression was maximal at 45 min of cold ischemia and decreased by 120 min. The expression at 120 min of cold ischemia correlated with markers of postreperfusion function, namely bile flow and SDH activity. During reperfusion a second distinct peak occurred at 180 min. Increased expression of NFkappaB at 180 min of reperfusion correlated directly with prior expression at 120 min during cold ischemia and with increased SDH activity. These data indicate that nuclear expression of NFkappaB demonstrate two distinct peaks of activity, one during cold ischemia and one after reperfusion. Enhanced expression of NFkappaB during cold ischemia not only correlates directly with NFkappaB expression during reperfusion, but also correlates inversely with postreperfusion graft function.

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PubMed2000

Cold ischemia in the absence of alloreactivity induces chronic transplant nephropathy through a process mediated by the platelet-activating factor.

BACKGROUND: Ischemia-reperfusion injury is considered a risk factor for the development of chronic transplant nephropathy (CTN) although the mechanisms that mediate its effects have not been completely established. We have previously shown that treatment with a platelet-activating factor (PAF) receptor antagonist (UR12670) protected kidneys from the progression to chronic nephropathy induced by warm ischemia. Here we examine the contribution of cold ischemia to the development of late functional and structural kidney changes in rats subjected to syngeneic renal transplantation and the role of PAF in this chronic nephropathy. SUBJECTS AND METHODS: Lewis rats were used as kidney donors and recipients, which were transplanted either immediately or after a cold ischemia period of 5 hr. Contralateral nephrectomy was performed on the seventh day after transplantation. Cyclosporine was administered for 15 days after transplantation. Groups were as follows: Sy, immediate transplantation; SyI, transplantation after 5 hr of cold ischemia; SyIUr, transplantation after 5 hr of cold ischemia plus UR12670 from the transplantation day to the end of the study, at 24 weeks. Serum creatinine, creatinine clearance, and proteinuria were determined every 4 weeks. Urinary

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PubMed2005

[Recent advances in the comprehension of the effects of cold ischemia in kidney graft].

Cold ischemia is the best known method to preserve kidneys for transplant. However, it produces several detrimental effects. First, cellular necrosis. Secondarily, during the hypothermic period a mitochondrial injury process develops which makes the cell entering a pre-apoptotic state. This apoptosis occurs definitively in the reperfusion. Preservation solutions currently available are not perfect and are not able to avoid cold-related cell injuries. The addition of certain substances to UW solution (desferrioxamine) has shown experimentally a reduction in mitochondrial cold-related lesions. Isolated hypothermic kidney perfusion reduces initial graft dysfunction about 20% in comparison to hypothermic storage. This fact relates to important either economical as functional consequences.

Adenosine↗

PubMed2004

Cold ischemia and the reduced long-term survival of cadaveric renal allografts.

BACKGROUND: Prolonged cold ischemia time (CIT) is accompanied by delayed cadaveric renal allograft function and early allograft loss, but the effect of CIT on long-term allograft survival is less certain and has not been studied in detail. METHODS: Using data from the United Network for Organ Sharing, we identified 6465 patients who received a kidney-only transplant of cadaveric origin for the first time in 1995. We examined the effect of CIT on the 6-year survival of these kidneys using Cox proportional hazard analysis. RESULTS: The mean CIT of the kidney was 21 +/- 7 hours (mean +/- SD) and correlated with the serum creatinine on discharge (R= 0.20, P < 0.001) and the distance traveled by the kidneys (R= 0.30, P < 0.001). CIT had a significant effect on the 6-year allograft survival (a 10-hour increase in CIT was associated with a hazard risk ratio (RR) of 1.20 for graft failure (P < 0.001) that persisted (RR = 1.40, P= 0.021) after adjusting for donor age, recipient age and race, human leukocyte antigen (HLA) mismatch, panel reactive antibodies, and first 6 months' rejection treatments. Similarly, compared to CIT category of 0 to 10 hours, the 6-year graft survival was progressively worse for 11 to 20 hours (RR = 1.03), 21 to 30 hours (RR = 1.12), and, significantly so, for >30 hours (RR = 1.32; P= 0.011). The gain in HLA match with increasing CIT was not uniform; for instance, HLA match in >30 hours was lower than for 21 to 30 hours (2.4 +/- 1.5 vs. 2.7 +/- 1.6; P < 0.001). CONCLUSION: (1) Cadaveric kidneys continue to undergo prolonged periods of cold ischemia; (2) prolonged cold storage is associated with longer distance traveled by the kidneys, but is not associated with any significant gain in tissue matching; and (3) prolonged cold ischemia is a significant predictor of long-term graft loss. Reducing prolonged cold ischemia by regional distribution of organs and less stringent tissue matching may reduce the persistent high rate of long-term loss of cadaveric renal allografts.

Adult↗

PubMed2000

Marked difference in tumor necrosis factor-alpha expression in warm ischemia- and cold ischemia-reperfusion of the rat liver.

Although tumor necrosis factor-alpha has been implicated in liver injury after both warm ischemia- and cold ischemia-reperfusion, it is unclear whether reactivity of the liver to these stimuli is similar with regard to cytokine expression. Here we compare the effects of warm and cold ischemia on tumor necrosis factor-alpha expression and test the hypothesis that cold ischemia preceding warm ischemia causes overexpression of this cytokine. Rat livers were flushed out with University of Wisconsin solution and subjected to varying periods of warm ischemia, cold ischemia, or cold ischemia plus warm ischemia followed by reperfusion using a blood-free perfusion model. Tumor necrosis factor-alpha and interleukin-10 release into the perfusate and bile were measured by ELISA, and expression of these cytokines and that of c-fos, c-jun, and c-myc were studied by reverse-transcriptase polymerase chain reaction. We found high levels of tumor necrosis factor-alpha in the perfusates of livers subjected to warm ischemia-reperfusion, whereas minimal or no tumor necrosis factor-alpha was detected in livers subjected to cold ischemia-reperfusion or to cold ischemia plus warm ischemia-reperfusion. Reverse-transcriptase polymerase chain reaction confirmed the above findings and showed that immediate early genes were expressed in reperfused groups of livers. Measurements of cytokine release into bile showed that neither tumor necrosis factor-alpha nor interleukin-10 were upregulated by cold ischemia-reperfusion. The results suggest that (1) warm ischemia- and cold ischemia-reperfusion of rat liver lead to very different outcomes with regard to tumor necrosis factor-alpha expression and (2) cold ischemia preceding warm ischemia prevents upregulation of tumor necrosis factor-alpha.

Animals↗

PubMed2005

Prolonged cold ischemia in rat cardiac allografts promotes ischemia-reperfusion injury and the development of graft coronary artery disease in a linear fashion.

BACKGROUND: Prolonged cold ischemia is thought to exacerbate ischemia-reperfusion injury and graft coronary artery disease (GCAD). We investigated the effect of varying lengths of cold ischemia on inflammation and apoptosis during ischemia-reperfusion injury and correlated this with the degree of GCAD in rat cardiac allografts. METHODS: PVG rat (RT1c) hearts subjected to 30, 60, 90, 120, or 150 minutes of cold ischemia were heterotopically transplanted into ACI rats (RT1a). Grafts were procured after 4 hours of reperfusion and analyzed for superoxide generation, myeloperoxidase activity, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and monocyte chemoattractant protein-1/chemokine (C-C motif) ligand 2 (MCP-1/CCL2) production, cardiomyocyte apoptosis, and caspase-2, -3, -8, -9 activities. Additional transplanted animals received cyclosporine A (7.5 mg/kg/day) for 10 days as chronic rejection models. Indices of GCAD were determined at 90 days. RESULTS: A direct linear correlation was found between cold ischemic time, ischemia-reperfusion injury, and GCAD. Superoxide generation, myeloperoxidase activity, TNF-alpha, IL-1beta, MCP-1/CCL2 production, cardiomyocyte apoptosis, and caspase-2, -3, -8, and -9 activities increased with ischemic time, peaking at 120 minutes and plateauing at 150 minutes. GCAD, assessed by the percentage of luminal narrowing, the intima/media ratio, and the percentage of diseased vessels, worsened with increased ischemic time, peaking at 120 minutes and plateauing at 150 minutes. All tested variables in both the acute and chronic phases were significantly increased with 120-minute ischemia compared with 30-minute ischemia. CONCLUSIONS: These data indicate that the degree of cardiomyocyte apoptosis and inflammatory response in cardiac allografts during ischemia-reperfusion injury depends on the duration of cold ischemia. More important, that prolonged cold ischemia correlates with increased GCAD.

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PubMed2006

Long-term functional outcome of renal units after laparoscopic nephron-sparing surgery under cold ischemia.

BACKGROUND AND PURPOSE: Renal-artery occlusion is used to control bleeding during laparoscopic nephronsparing surgery, but there are worries about ischemic damage. We compared the functional outcomes of kidneys treated under warm and cold ischemia. PATIENTS AND METHODS: Twelve patients treated with warm ischemia and 14 treated with cold ischemia had renal function investigation 3 to 6 months postoperatively. Four and ten patients, respectively, also had preoperative studies. RESULTS: In patients treated with warm ischemia, two kidneys had evidence of possible damage, but the kidney with the longest ischemia (56 minutes) was normal. Among patients treated with cold ischemia, function was lost in one case. Parenchymal transit time was prolonged in five patients, but in four cases, this probably was attributable to performance of a contrast-enhanced CT scan the same day. In the fifth patient, an ischemic injury is possible. CONCLUSION: The parenchymal transit time is a good indicator of ischemic damage. Nephron-sparing surgery can lead to damage even if the ischemia time is short and cold ischemia is used. More data are needed on the factors determining such injury.

Aged↗

PubMedDate not supplied

Ex vivo evaluation of organ function after cold ischemia.

An ex vivo perfusion of kidneys was performed at 34 degrees C after cold ischemia of 24, 48, 72, and 96 hours to evaluate organ function prospectively. The prospective evaluation of organ function followed static hypothermic storage of the kidneys in a solution representative of clinical organ preservation. The warm perfusion was performed with an acellular solution that supports oxidative metabolism of sufficient magnitude to restore urine flow ex vivo. The parameters of organ function evaluated included oxygen consumption, vascular resistance, urine flow, and glomerular filtration rates, which were correlated with the histologic findings. The results of this study suggest that kidneys exposed to 24 and 48 hours of cold ischemia demonstrated oxygen consumption rates and vascular dynamics similar to control kidneys without exposure to cold ischemia, indicating cell viability. When the cold ischemic period was increased beyond 48 hours of preservation, substantially reduced rates of oxygen consumption and increased vascular resistances were observed, representing a loss of viability confirmed histologically. However, organ function was found to be impaired after exposure to cold ischemia at every time point. These results suggest that cold ischemic exposure had a negative impact on immediate renal function once oxidative metabolism was restored, which was exacerbated as the cold ischemic period was extended. Furthermore, these findings suggest that although the renal cells were viable after cold ischemic exposure, the viability status did not result in immediate function. Therefore, assessment of an organ based solely on cell viability may falsely indicate a functional organ. It will be necessary to identify parameters of organ function that can distinguish reversibility from non-reversibility of cellular impairment to distinguish permanent functional disturbances. The ability to predict organ function prospectively will be an important aspect of any effective future expansion of the organ donor pool.

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PubMedDate not supplied

[Effect of time of vascular anastomosis and of hot and cold ischemia, on survival of cadaver renal graft].

A retrospective study was performed on our series of 240 primary cadaveric renal transplant recipients to dissect the influence of vascular anastomosis time, warm ischemia time and cold ischemia time on ultimate graft survival. 177 patients received conventional immunosuppression with Azatioprine and steroids, and 63 patients received Cyclosporine A therapy. The data was analyzed for sub-groups of ischemia time and comparisons were performed using the method of Tarone-Ware. The present study fails to demonstrate a detrimental effect of ischemic insults on graft survival. The use of Cyclosporine A in the pre and post-transplant, monitoring periodically serum cyclosporine levels and the use of renal allograft biopsy, allows the use of this agent without a high incidence of nefrotoxicity.

Adult↗

PubMed2002

Gene expression profiling of prolonged cold ischemia and reperfusion in murine heart transplants.

BACKGROUND: Heart transplantation causes complex changes in the biological homeostasis of the graft. Current knowledge is restricted to a few genes and regulation of certain factors involved in ischemia-reperfusion (I/R) injury. Efficient strategies to prevent I/R injury, however, require a better understanding of its mechanisms. Using cDNA microarrays, we investigated gene expression profiles of murine cardiac isografts. METHODS: For microarray hybridization experiments, chips with 8,734 individual target sequences were used. Messenger RNA was extracted from hearts subjected to warm ischemia and different time periods of reperfusion or to prolonged cold ischemia or warm ischemia and transplantation. Native hearts served as controls. RESULTS: A set of 68 sequences was regulated in all hearts. In addition, grafts without cold ischemia showed differential expression of 65 sequences, which were not found in hearts transplanted after cold storage, and which in turn had 38 sequences regulated and not detected in grafts without cold ischemia. Overall, approximately 50% of regulated transcripts are expressed sequence tags (ESTs) with unknown function. Annotated genes encoded immune modulators (20% of sequences), receptor proteins, structural proteins, and proteins involved in metabolism. CONCLUSION: Our data demonstrate expression profiles of hearts subjected to prolonged cold ischemia or transplantation in an isogeneic setting. We have defined functional complexes and detected a substantial amount of ESTs encoding novel proteins. These studies may provide a molecular basis for further functional experiments and may help identify potential targets for modulation of postischemic inflammation.

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