Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of true cold ischemia times (CIT) and rewarming ischemia times (WIT) in determining outcome after liver transplantation was investigated in 230 adult recipients. Using multivariate analysis, WIT (time from the start of implantation until restoration of arterial and portal blood supply) and donor intensive care stay (P = .04 and .0004, respectively) but not CIT (the time from donor portal vein flushing until the graft was removed from University of Wisconsin solution; P > .30) emerged as independent determinants of graft survival. In the small number of patients with a WIT of greater than 180 minutes, there were reductions in graft survival (58% v 80% for WIT greater than 180 minutes) but these just failed to reach significance (P = .055). CIT had no influence on graft survival using cut-offs of 12 or 18 hours. A WIT of greater than 180 minutes was associated with an increased median area under the curve of day 1 through 7 serum bilirubin (1,370 v 915 mumol/L.day; P = .048) and trends towards an increased incidence of primary graft nonfunction or dysfunction (22.2% v 6.2% for WIT of less than 180 minutes; P = .065) and the day 1 through 7 area under the curve of serum aspartate aminotransferase (3,310 v 1,440 IU/L.day; P = .092). A prolonged CIT (greater than 18 hours) led to a prolonged hospital stay (69 v 31 days; P = .03), an increased area under the curve of day 8 through 14 serum bilirubin (2,500 v 995 mumol/L.day; P = .003), and a trend towards an increased incidence of initial poor graft function (33.3% v 6.3% for less than 18 hours; P = .092). The incidence of acute rejection increased (to 64.3% from 53.4%; P = .04) in patients with preservation injury (serum aspartate aminotransferase greater than 1,500 IU/L during the first 2 postoperative days). True CIT and WIT are important determinants of outcome after liver transplantation.
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PMID:Contribution of true cold and rewarming ischemia times to factors determining outcome after orthotopic liver transplantation. 934 86

This study investigated the role of Kupffer cells on survival and graft injury in transplanted fatty livers from rats treated acutely with ethanol. Donor rats were given ethanol (5 g/kg, by mouth) 20 hours before explantation, and liver grafts were preserved in University of Wisconsin cold storage solution for 24 to 42 hours prior to implantation. Blood samples were taken from the inferior vena cava for 3 hours after implantation. During this time, serum aspartate transaminase levels increased gradually from 122 U/L to 597 U/L in control rats, while ethanol treatment elevated values to 2,278 U/L. Gadolinium chloride (20 mg/kg, given intravenously to recipients 24 hours before explantation), a selective inactivator of Kupffer cells, minimized the increase in aspartate transaminase levels significantly. After implantation of grafts cold-stored for 42 hours, survival rates were 88% in control rats but only 33% in ethanol-treated rats. Gadolinium chloride improved survival nearly to control values. Ethanol nearly doubled white blood cell adhesion, an effect also largely blocked by gadolinium chloride. Further, alpha-(4-pyridyl 1-oxid)-N-tert-butylnitrone radical adducts detected in the bile were increased twofold by ethanol treatment. This effect was also reversed by gadolinium chloride. Taken together, these data indicate that survival is poorer and graft injury is greater in fatty livers from ethanol-treated rats. Inactivation of Kupffer cells minimized graft damage, most likely by improving hepatic microcirculation and diminishing lipid peroxidation.
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PMID:Destruction of Kupffer cells increases survival and reduces graft injury after transplantation of fatty livers from ethanol-treated rats. 934 80

Little is known about the possible contribution of apoptosis to ischemia-reperfusion injury in human liver transplantation. Therefore, we studied postreperfusion surgical biopsy specimens of 16 human liver allografts using the TUNEL assay for in situ demonstration of apoptotic cells. In all patients, a variable proportion of hepatocytes and sinusoidal endothelial cells presented labeled nuclei. The mean +/- standard deviation percentages of positive hepatocytes were 18.7% +/- 12.2% in the whole section, 30.4% +/- 18.7% in the subcapsular region, 14.5% +/- 13.5% in the centrilobular zones, and 10.3% +/- 9.5% in the periportal zones. The percentage of positive hepatocytes were not correlated with the duration of cold ischemia but was higher in grafts harvested from donors with elevated preoperative aspartate aminotransferase (AST) levels. The percentage of positive hepatocytes was correlated with postoperative serum levels of AST (P = .015) and inversely correlated with postoperative serum levels of factor V (P = .019). Apoptotic biliary epithelial cells were detected in only 3 cases. In conclusion, apoptosis is a frequent event in postreperfusion biopsy specimens of liver allografts and probably contributes to preservation injury of hepatocytes.
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PMID:Apoptosis after ischemia-reperfusion in human liver allografts. 934 71

Donor pretreatment is a new concept in organ preservation. Pentoxifylline (PTX) has been reported to suppress the activation of Kupffer cells and to decrease injury to the hepatic graft after rat liver transplantation. We evaluated the efficiency of PTX pretreatment on the donor against hepatic injury following cold ischemia (CI) or warm ischemia (WI) using the rat liver transplantation model. Dose dependency: every rat was injected intraperitoneally with PTX (30, 50, or 80 mg/kg) or saline. One hour later, the portal vein (PV) and the hepatic artery (HA) were clamped for 30 min. Transplantation: the donor rat was injected intraperitoneally with 50 mg/kg PTX or saline, 1 hr before laparotomy. Animals were divided into two groups. In the CI group, grafts were preserved for 12 hr in University of Wisconsin solution at 4 degrees C and transplanted. In the WI group, the PV and the HA in the donor were clamped for 30 min before donor surgery, and the grafts were transplanted. Serum levels of tumor necrosis factor-alpha (TNF-alpha), glutathione S-transferase-alpha (GST-alpha), and aspartate transaminase (AST) were measured at 30 min, 3 hr, and 24 hr after reperfusion of the PV. Compared with those of a control group, the serum levels of TNF-alpha, GST-alpha, and AST in the PTX-pretreated groups were significantly lower after both CI and WI at 30 min and further suppressed in the WI group at 24 hr. These results indicate that PTX pretreatment on the donor is effective for suppression of hepatic injury after both CI and WI.
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PMID:Efficiency of pentoxifylline in donor pretreatment in rat liver transplantation. 935 39

Continuous warm blood cardioplegia was widely used, as an effective means of myocardial preservation, in open heart surgery. The comparisons of myocardial protective effects between traditional cold crystalloid and warm blood cardioplegia, however, have been based mainly on hemodynamics, cardiac function and myocardial metabolism, other than clinical outcome. The present study was designed to examine myocardial protective effects by assessing clinical outcome, enzyme levels and myocardial cytochemistry. Twenty patients undergoing heart valve replacement were divided randomly into two groups: Group I was given intermittent perfusion of cold crystalloid (St. Thomas Hospital solution) with hypothermic cardiopulmonary bypass (CPB) and Group II was given continuous administration of warm blood cardioplegia with normothermic CPB. The groups were similar with respect to sex, age, body surface area and preoperative ventricular function. Blood samples were obtained from an indwelling radial arterial catheter or from the arterial end of the oxygenator. Biopsy specimens from the right atrium were obtained immediately before aortic declamping (ischemic period) and 30 minutes after crossclamp removal (reperfusion period). Serum enzymes, including alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and its isoenzymes and creatine phosphokinase (CK) and its isoenzyme, were determined. Myocardial cytochemistry were chiefly assessed by grey-scale image processing of adenosine triphosphatase (ATPase), succinate dehydrogenase (SDH) and cytochrome oxidase (CCO) examinations. Relations among the results were discussed. Reperfusion time was reduced and ventilation support time decreased in Group II (33.50 +/- 3.78 min vs. 25.00 +/- 4.46 min, p < 0.05; 38.98 +/- 16.55 h vs. 19.84 +/- 1.11 h, p < 0.05). Rates of atrial beating during aortic crossclamp and spontaneous recovery to normal sinus rhythm were much higher in Group II than in Group I (80% vs. 20%, p < 0.05; 70% vs. 10%, p < 0.05). Differences in hospital morbidity and mortality between groups were nonsignificant. Serum AST, ALT, LDH and LDH1 + LDH2 all showed no significant intergroup differences. There was a higher serum CK-MB level with a delayed peak in Group II. The cytochemistry activities of ATPase was not different between groups and periods and SDH was the highest during reperfusion period in Group I and of CCO significantly much promoted in Group II in both periods. Continuous warm blood cardioplegia resulted in higher spontaneous recovery to sinus rhythm, shorter reperfusion and ventilation support time. Damage to the myocardium, skeletal muscle and liver always occur in warm blood cardioplegic patients. However, warm blood cardioplegia is still a practical method for myocardial preservation in open heart surgery.
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PMID:A generalized consideration of myocardial preservation with cold crystalloid versus warm blood cardioplegia in heart valve replacement. 961 11

Liver transplantation (Ltx) has become a routine procedure for patients with end-stage liver disease. Despite ongoing progress on short- and long-term graft survival, primary dysfunction (PDF) remains a major problem. PDF is significantly associated with the duration of cold ischemia- and, possibly, with reperfusion-related injury. Nitric oxide (NO) has many physiological functions and plays an important role in modulating tissue injury. However, the mechanism of NO action in ischemia/reperfusion injury after Ltx is thus far unknown. In this study we investigated the role of inducable NO synthase (iNOS) in the liver after preservation with UW solution using the orthotopic Ltx model in the rat. Male Brown Norway rats were used for the Ltx procedure. After donor hepatectomy, livers were stored on ice-cold UW solution for 24 or 40 h and subsequently transplanted. A control group consisted of rats with Ltx after less than 1 h storage. Post-transplant blood samples were taken at 48 h to determine standard parameters for liver injury (aspartate transaminase, lactate dehydrogenase). Liver biopsies were obtained for detection of expression of iNOS (western blot) 24 and 48 h post-transplant. We observed that a preservation time of 24 h in UW solution presents no problem for graft survival after Ltx in rats with some brain function and in healthy animals. After 40 h preservation, liver damage is obvious and graft survival reduced, indicating the limits of cold storage may be within reach. With longer preservation times, more NOs was detected in liver tissue. This finding suggests that NO has a role in ischemia/reperfusion-related injury. Current intervention with NOS inhibitors will reveal whether NO has a negative or a positive effect on graft survival after Ltx.
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PMID:Extended preservation and effect of nitric oxide production in liver transplantation. 966 72

Hepatic allograft rejection remains an important problem following liver transplantation, and, indeed, complications related to the administration of immunosuppressive therapy remain a predominant cause of posttransplantation morbidity and mortality. The Liver Transplantation Database (LTD) was used to study a cohort of 762 consecutive adult liver transplantation recipients and determined the incidence, timing, and risk factors for acute rejection. We also evaluated the impact of histological severity of rejection on the need for additional immunosuppressive therapy and on patient and graft survival. Four hundred ninety (64%) of the 762 adult liver transplantation recipients developed at least one episode of rejection during a median follow-up period of 1,042 days (range, 336-1,896 days), most of which occurred during the first 6 weeks after transplantation. Multivariate analysis revealed that recipient age, serum creatinine, aspartate transaminase (AST) level, presence of edema, donor/recipient HLA-DR mismatch, cold ischemic time, and donor age were independently associated with the time to acute rejection. An interesting observation was that the histological severity of rejection was an important prognosticator: the use of antilymphocyte preparations was higher, and the time to death or retransplantation was shorter, for patients with severe rejection. Findings from this study will assist in decision-making for the use of immunosuppressive regimens and call into question whether complete elimination of all rejection or alloreactivity is a desirable goal in liver transplantation.
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PMID:Acute hepatic allograft rejection: incidence, risk factors, and impact on outcome. 973 52

Intracellular-type electrolyte solutions were introduced into organ preservation to prevent K+ efflux and Na+ and Cl- influx into cells and cell swelling during cold ischemia. We studied cation accumulation in the interstitial space by microdialysis, during rat liver cold storage and after flush-out with high-K+ and low-K+ solutions. The effect of Na+ and K+ on graft function and survival was studied in an isolated perfused liver model and an orthotopic transplantation model after rat liver storage in iso-osmolar high-K+ and low-K+ solutions. After 24 hours of cold ischemia [Na+]o dropped from 136 +/- 2 mmol/L to 91.8 +/- 1.1 mmol/L, and [K+]o increased from 5.9 +/- 0.1 mmol/L to 12.2 +/- 1.6 mmol/L (P < .001 vs. control). [Na+]o and [K+]o after flush-out did not equilibrate with [Na+]sol and [K+]sol after 24 hours of cold storage. Rat livers preserved in low-K+ solutions produced significantly more bile during isolated reperfusion and released less alanine transaminase, aspartate transaminase, and lactate dehydrogenase into the reperfusion medium than high-K+ solutions. Rat liver survival after 14 hours of preservation was higher in low-K+ solutions (13 of 13) than in high-K+ solutions (7 of 13). Those studies indicate that during cold storage of rat livers, transmembraneous Na+-K+ sodium-potassium exchange might not follow the 3:2 stochiometry of a sole sodium-potassium exchange via Na+-K+ sodium-potassium adenosine triphosphatase (ATPase), and that low-K+ solutions might improve graft function and survival after rat liver preservation.
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PMID:Interstitial accumulation of Na+ and K+ during flush-out and cold storage of rat livers: implications for graft survival. 979 18

The purpose of this paper was to assess the role of continuous warm blood cardioplegia in heart valve replacement in comparison with standard intermittent cold crystalloid cardioplegia. Twenty patients undergoing open heart valve replacement were divided arbitrarily into two groups in this study; Group I was given intermittent perfusion of cold crystalloid (St. Thomas Hospital solution) with hypothermic cardiopulmonary bypass (CPB) (10 patients) and Group II was given continuous administration of warm blood cardioplegia with normothermic CPB (10 patients). The groups were similar with respect to sex, age, body surface area and preoperative ventricular function. Bypass conditions as well as perioperative complications were evaluated in the respective groups. Peak values of the serum enzyme levels within 120 hours of postoperation including alanine transaminase, aspartate aminotransferase, lactate dehydrogenase (LDH) and its isoenzymes LDH1 + LDH2, phosphokinase (CK) and its isoenzyme CK-MB, superoxide dismutase, and malondialdehyde in the two groups were also assessed. Biopsies from the right atrium were obtained immediately before aortic cross clamp removal (ischemic period), and 30 minutes after cross clamp removal (reperfusion period). Myocardial structures were observed and scored. No significant intergroup differences were found in the bypass conditions except for the perfusion flow, systemic temperature and central venous pressure. There were no significant differences in the intergroup perioperative complications, either. Serum enzymes except CK which reached peak values in Group I appeared prior to or consistent with Group II. There were no significant intergroup differences in peak levels of the serum enzymes except CK (307.44 +/- 38.56 U/L vs. 466.29 +/- 52.03 U/L, p = 0.039 for CK). From the pathological assessment, the structural alterations were the most severe during the reperfusion period in group I. Myocardial damage showed more severely in reperfusion than in ischemia in both. Warm blood cardioplegic technique, raising potential hazards, is still a practical method for myocardial protection in open heart surgery, but might be less effective in protecting the tissues beyond myocardium.
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PMID:Benefits and pitfalls of warm blood cardioplegia in heart valve replacement: systemic protective effects. 981 3

Cold preservation/reperfusion leads to sinusoidal endothelial cell (SEC) activation and damage in nearly every liver transplantation; the extent of these changes influences early graft function. Upon reperfusion, activated SEC show increased expression of adhesion molecules, including von Willebrand factor (vWF) which is released into the circulation. This study was designed to evaluate the levels of vWF measured in the caval effluent and correlate these findings with known markers of SEC damage and early graft function. Data were obtained from 35 patients undergoing orthotopic liver transplantation (LTx). Two samples were taken from each patient for measurement of vWF: a) from the portal vein immediately prior to reperfusion; and b) from the first 50 ml of the caval effluent. Commercial assays were used to measure vWF, as well as hyaluronic acid (HA), thrombomodulin (TM), IL-1 beta, IL-6, IL-8 and TNF-alpha. Patients were divided into two groups based on early graft function. Poor early graft function (PEGF) was defined as a peak aspartate transaminase (AST) or alanine transaminase (ALT) level > 2500 U/L during the first three postoperative days (POD) and a prothrombin time (PT) > 16 s on POD 2 (n = 8). The remaining 27 patients had good early graft function (GEGF). In patients with GEGF, vWF levels dropped significantly between the two time points. This change was not observed in those with PEGF. A positive linear correlation was observed in the PEGF group between vWF and HA and IL-6. The different pattern of change in vWF between the two groups, as well as the positive correlation between HA, IL-6 and vWF in PEGF, suggest that vWF may be a useful marker of early graft function.
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PMID:Correlation between von Willebrand factor levels and early graft function in clinical liver transplantation. 1008 31


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