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Query: UMLS:C0009443 (cold)
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In a group of 276 consecutive liver transplants 8 primary graft nonfunctions were identified (2.9%). Recipients showed a progressive elevation of transferases (mean maximum value ALT: 5000 +/- 1892 U/l) and bilirubin (mean maximum value: 20 +/- 11.8 mg/dl) and a decrease in the percent prothrombin time (mean minimum value 26 +/- 13 min.) in the post-implantation survival time of the 8 grafts (range 1-5 days). No statistically significant differences were observed between mean cold and warm-ischemia times for these 8 donor organs and those of a control group of 92 consecutive grafts. All organs except one were ABO isogroup and all except another one displayed negative lymphocytotoxic crossmatch. Predominantly small-droplet hepatocytic vacuolization with no nuclear displacement was observed in plastic-embedded semithin sections of all post-primary nonfunction liver tissues (severe in 4 grafts, centri-mediozonal in 2, and centrolobular in 2). In 3 cases where fresh liver tissue was available the lipidic nature of the vacuoles was confirmed with electron microscopy and with frozen sections stained with Sudan III. Other microscopic lesions were also observed: spotty monocellular coagulative necroses, variable extension of zonal coagulative necroses and hemorrhages, cholestasis and minor mixed inflammatory infiltrate. Comparative microscopic study of these tissues with the protocol biopsy specimens obtained 2-4 hours after reperfusion demonstrated previous liver cell-vacuolization in only 3 cases. In conclusion, an acute progressive microvascular steatosis developed in this primary nonfunction series. No specific etiopathogenic factors were identified.
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PMID:A clinopathologic review of 8 liver graft primary nonfunctions. 759 May 68

For the assessment of graft viability, serum hyaluronic acid (HA) levels during porcine orthotopic liver transplantation were measured in two groups: group 1 (viable: n = 5) in which allografts were transplanted following a minimal cold (4 degrees C) preservation, and group 2 (nonviable: n = 4) in which allografts were transplanted after cold static storage (4 degrees C) for 24 h in University of Wisconsin solution. The changes in the HA levels reached a significant difference between the two groups at 30 min after reperfusion (P < 0.02). In group 1, all animals survived for over 4 days, while all animals in group 2 died within 24 h. The serum HA also demonstrated a significant correlation with prothrombin time, beta-glucuronidase, and aspartate aminotransferase at 120 min after reperfusion. These results suggest that the measurement of serum HA is a potentially effective index for evaluating hepatic allograft viability.
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PMID:Serum hyaluronic acid for the assessment of graft viability in porcine liver transplantation. 798 43

Endothelial release of tissue plasminogen activator (t-PA) may initiate fibrinolysis. Fibrinolysis and coagulation were investigated in 12 patients undergoing elective coronary artery bypass surgery. Cardiopulmonary bypass (CPB) was 108 +/- 7 min (mean +/- SEM), the time of cold, crystalloid, retrograde cardioplegia 53 +/- 5 min. Arterial and coronary sinus blood were sampled concomitantly before cardioplegia and after release of the aortic cross-clamp, for measurement of t-PA antigen (Ag) and activity, plasminogen activator inhibitor (PAI-1) Ag and activity, t-PA/PAI-1 complex, single chain urokinase (sc-uPA) and urokinase (uPA) plasminogen activators, the fibrin split product D-dimer, thrombin-antithrombin complex (TAT), and the prothrombin split product F 1 + 2. Cardiopulmonary bypass significantly increased t-PA Ag and activity, t-PA/PAI complex, D-dimer, TAT, and F 1 + 2, and decreased PAI-1 Ag and activity in arterial blood; uPA and sc-uPA were unchanged. The tissue plasminogen activator antigen was higher in coronary sinus than arterial blood after 1 (39 +/- 5 vs 24 +/- 4 ng/ml, P < 0.003), 4 (P < 0.003), and 10 min (P < 0.004) reperfusion. Tissue plasminogen activator activity and t-PA/PAI complex increased, PAI-1 activity decreased, while all other parameters were unchanged across the coronary circulation. In conclusion, CPB induces fibrinolysis and coagulation. Cold cardioplegia induces t-PA release in the coronary circulation, denoting a postischemic antithrombotic function of the coronary endothelium. Tissue plasminogen activator may be used to evaluate endothelial stimulation or injury induced by CPB, or by different regimens of myocardial protection.
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PMID:Fibrinolysis during cardiac surgery. Release of tissue plasminogen activator in arterial and coronary sinus blood. 808 78

It is well recognized that current selection criteria used to assess liver grafts before implantation are inaccurate and correlate poorly with graft outcome. A bench or laboratory-based test that could indicate the extent of liver injury immediately before implantation would be a valuable adjunct to clinical assessment. Hyaluronic acid (HA) and creatine kinase (BB component; CK-BB) levels in the caval effluent after liver perfusion have been suggested as indicators of preservation injury. Our objective was to investigate the relevance of preserved liver effluent HA and CK-BB as a predictor of early graft function. Perfused liver effluent HA and CK-BB levels were measured. Graft function was measured in terms of peak serum aspartate transaminase and its level on day 5 postoperatively as well as peak bilirubin level and prothrombin time. The cold ischemia time (CIT) was recorded. Statistical comparisons were made among HA level, CK-BB level, CIT, and graft function parameters. The study was conducted at The Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom. Fifty patients undergoing OLT were studied. HA level was measured in 50 patients and CK-BB level in 30 patients. The main outcome measures were graft function and graft outcome. The graft function data are grouped according to effluent HA levels above or below 400 micrograms/L. Thirteen patients (26%) had a level below 400 micrograms/L and the remaining 37 (74%) were above this threshold. There were no significant differences between the groups for these indicators of graft function. There was no difference between the 2 groups for CIT. The overall median HA level was 1212 micrograms/L (range 39-4000 micrograms/L). The median total CK activity in the perfusate was 302 IU/L (range 118-1155 IU/L). The proportion of CK-BB activity from this total was 146 IU/L (8-641 IU/L), or 48% of the total CK activity. In a multiple regression analysis with CK-BB activity as the dependent variable, there was no demonstrable numerical relationship to graft function. In a separate multiple regression analysis similar results were obtained for HA. We conclude that the level of HA or CK-BB levels should not be used in determining the suitability for implantation of a harvested hepatic allograft.
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PMID:Can effluent hyaluronic acid or creatine kinase predict sinusoidal injury severity after cold ischemia? 827 99

A review of 550 consecutively transplanted liver grafts stored in University of Wisconsin solution (UW) was performed during a 4-year period to ascertain whether graft function was impaired by flushing the aorta with Eurocollins (EC) rather than UW during the harvesting. The outcome of 255 liver grafts flushed with UW in both the aorta and portal vein (group UW/UW) was compared with 295 liver grafts flushed with EC through the aorta and UW through the portal vein (group ECUW). Liver grafts in both groups were flushed with 1 L of UW during the back table procedure and subsequently stored in UW at 4 degrees C before transport. Donor and recipient characteristics, cold and warm ischemia times, and methods of transplantation were similar in both groups, except that the recipient prothrombin time (PT) before liver transplantation (LT) was lower in the UW/UW group. There was no significant difference between the groups with peak transaminases aspartate aminotransferase (AST) and alanine aminotransferase, maximum value of serum bilirubin within 10 days following LT, incidence of primary nonfunction, need for retransplantation, and patient and graft survival at 1 month. Results were improved, however, in the EC/UW group in regard to PT after LT, operative bleeding and proportion of grafts with histologic lesions at the reperfusion biopsy (P<0.001). These better results in the EC/UW group were confirmed when grafts transplanted in urgent situations were excluded from analysis and by multivariate analysis assessing the effects of pretransplant PT and AST values of the recipients combined with the method of liver cooling with each of the aforementioned criteria. In conclusion, the method of using EC for the aortic flush during liver procurement reduces the amount of UW solution by 50% with improved graft function. This method seems justified in that it is less expensive while affording improved graft function.
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PMID:Beneficial effects of Eurocollins as aortic flush for the procurement of human livers. 860 71

The aim of this study was to analyze the donor risk factors associated with second orthotopic liver transplantation (reOLT) and graft loss after OLT within 1 month. A total of 649 OLTs performed in 11 centers in Spain during the period from 1992 to 1993 were analyzed retrospectively. Eleven donor and recipient variables were studied. Biochemical evolution of the OLT, biliary and arterial complications, patient status (alive, retransplanted, or dead), and follow-up were also recorded. Bivariate study demonstrated that extended preservation ( > 12 hr) was associated with increased biliary complications (P = 0.02), and lower prothrombin time (P = 0.04). In a logistic model regression for biliary complications, ischemia > 12 hr was an independent risk factor (odds ratio = 2.2, 95% confidence interval [CI] = 1.1-4.3). The multivariate Cox proportional model of potential risk factors showed that only urgent reOLT (relative risk [RR] = 2.7, 95% CI = 1.4-5.4) was independently associated with higher 30-day mortality. Donor plasma sodium > 155 mmol/L (RR = 1.4, 95% CI = 1.0-2.2) and incompatible ABO graft (RR = 3.2, 95% CI = 1.3-7.9) were independently associated with increased rate of reOLT before 30 days. Donor plasma sodium > 155 mmol/L (RR = 2, 95% CI = 1.1-3.6) and incompatible graft (RR = 3.3, 95% CI = 1.4-8.2) were independently associated with graft loss (death or reOLT) before 1 month. We conclude that cold ischemia should be kept less than 12 hr in order to avoid biliary complications. Donors over 60 years old or with plasma sodium > 155 should be carefully evaluated before OLT.
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PMID:The deleterious effect of donor high plasma sodium and extended preservation in liver transplantation. A multivariate analysis. 861 Mar 52

Between March 1991 and August 1995, 36 livers from donors >/=70 years old were transplanted. In donors, we recorded the following risk factors: alanine aminotransferase > 120 and rising, dopamine dose > 15 microg/kg/min, hypotension (systolic blood pressure <80) >1 hr, stay in the intensive care unit >5 days and body mass index >/=27. In 35 recipients, we recorded pretransplant United Network for Organ Sharing (UNOS) status, cold/warm ischemia time, intraoperative blood loss, and occurrence of poor early graft function or primary nonfunction. Mean recipient age was 55 years (range, 25-75 years). Four recipients were UNOS status 1, 19 were UNOS 2, and 12 were UNOS 3. Two livers were used as second grafts for primary graft nonfunction. Mean donor age was 73 years (range, 70-84 years). Intracranial bleeding was the cause of death in the majority of donors. The 36 donors had 40 risk factors; 10 donors had >1 risk factor. Mean cold and warm ischemia times were 9:08 +/- 2:57 hr and 51 +/- 9 min. Mean total operative time was 7.5 hr. Posttransplant mean peak alanine aminotransferase and aspartate aminotransferase levels were 937.3 +/- 703.1 IU/L and 923.3 +/- 708.5 IU/L, respectively. Mean prothrombin time on postoperative day 2 was 14.9 +/- 1.6 sec. Average total bilirubin on postoperative day 5 was 4.9 mg/dl. Median length of stay in the intensive care unit was 4 days. One recipient had poor early graft function; two recipients had primary nonfunction. Mean follow-up was 503 days (range, 110-1714 days). Three-month actual graft and patient survival rates were 85% and 91%, respectively. One-year actuarial graft and patient survival rates were also 85% and 91%, respectively. We conclude that older livers can be used safely. Advanced donor age should not be a contraindication to liver procurement.
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PMID:Safe use of hepatic allografts from donors older than 70 years. 869 47

Seasonal influence on mortality from cardiovascular and cerebrovascular diseases is well documented. Understanding the seasonal variations in cardiovascular risk factors can shed light on this phenomenon. Elevation of coagulation factors during cold weather may in part explain the higher mortality from myocardial infarction and stroke in winter. The Cardiovascular Disease Risk Factors Community Study (CVDFACTS) included subjects belonging to 2 cohorts located in northern and southern Taiwan. This study included 2877 subjects aged 18 and above whose blood levels were examined for various coagulating factors. Besides measuring conventional cardiovascular risk factors including: blood pressure, body mass index and total cholesterol, values for blood fibrinogen, factor VII activity, factor VIII activity, plasminogen, antithrombin III, prothrombin time and activated partial thromboplastin time were determined for all subjects. Of these hemostatic parameters, levels of all, except prothrombin time, were statistically different between days with mean temperature > 20 degrees C and days with temperature < or = 20 degrees C (P < 0.01). In cold weather, a greater tendency to clot in circulatory system was demonstrated in this study, indicating seasonal variations may be demonstrated in this subtropical region.
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PMID:Values of blood coagulating factors vary with ambient temperature: the Cardiovascular Disease Risk Factor Two-Township Study in Taiwan. 890 10

Eighty liver allografts were studied to determine the predictive value of intraoperative biopsies and postoperative liver function tests for the development of preservation injury (PI). Peak transaminase (aspartate transaminase [AST] and alanine transaminase [ALT]) and prothrombin time (PT) values achieved by each patient during postoperative days (POD) 1 through 7 were determined. PI in day 0 preperfusion biopsies (0Pre) (obtained immediately before implantation) and postperfusion biopsies (0Post) (obtained immediately after revascularization) was categorized by histological criteria as present or absent. PI in biopsies taken during POD 2 through 14 was histologically graded as either moderate-to-severe, mild, or absent. Of the 80 allografts, 8 were omitted because of primary nonfunction or postoperative complications. 0Pre and 0Post biopsies were available on 25 of 72 (35%) and 69 of 72 (96%) allografts, respectively. Only 2 (8%) of the 0Pre biopsies showed histological PI compared with 48 (70%) of the 0Post biopsies. Fifty-nine patients were biopsied between POD 2 through 14. Of these, 15, 28, and 16 patients developed moderate-to-severe, mild, or no evidence of PI, respectively. The presence of PI in the 0Post biopsy strongly correlated with the development of PI during POD 2 through 14 (P < .0005). Peak AST and ALT values in patients with moderate-to-severe PI on POD 2 through 14 were significantly elevated compared with those patients with either mild (P = .01 and .03) or no PI (P = .02 and .006). Because of extensive overlap in AST and ALT values between the three groups, however, transaminase values were not useful in predicting the presence or absence of PI in the individual case. The development of PI during POD 2 through 14 correlated with advanced donor age (P = .06) but was unassociated with 0Pre biopsy findings, cold ischemia time, or peak PT values. We conclude that the 0Post biopsy is a valuable tool for the prediction of subsequent PI in the early postoperative period. In contrast, 0Pre biopsy findings and peak AST and ALT values are not useful in the assessment of PI.
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PMID:Predictive value of intraoperative biopsies and liver function tests for preservation injury in orthotopic liver transplantation. 898 88

An 81-year-old man known to have a stable cold agglutinin syndrome presented with a progressive cerebral hemorrhage. Coagulation tests revealed prolonged APTT and prothrombin time and severely decreased factor V activity, which could not be normalized by mixing with normal plasma. The patient appeared refractory to substitution with fresh-frozen plasma, suggesting the presence of a circulating inhibitor specific for factor V. To our knowledge, this is the first case of a lymphoproliferative disease leading to a cold agglutinin syndrome and a putative inhibitor of factor V. In patients with paraproteinemia presenting with bleeding diathesis, the presence of a circulating inhibitor of a specific coagulation factor must be considered.
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PMID:Factor V inhibitor associated with cold agglutinin disease. 948 26


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