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PubMedDate not supplied

Experience with hystidine tryptophan ketoglutarate versus University Wisconsin preservation solutions in transplantation.

We present our experience with histidine tryptophan ketoglutarate (HTK) and University Wisconsin (UW) preservation solutions in liver transplantation and a review of the literature in pancreas and kidney transplantation comparing these solutions. A group of 134 liver transplantations in 123 recipients was analyzed retrospectively. Grafts procured in adults were perfused with HTK in 63 cases and with UW in 71 cases. We compared results according to preoperative, intraoperative, and postoperative parameters, as well as complications and survival. No differences regarding donor and recipient data, intraoperative fresh frozen plasma (FFP) substitution, length of intensive care unit (ICU) stay, and ischemic damage of the graft were found. The rate of complications was comparable in both groups. However, the bilirubin was higher in the UW group. The rate of biliary complications was higher in the UW group (n = 8) versus the HTK group (n = 5). HTK ischemic type biliary lesions (ITBL) were only present in the UW group. Patient and graft survival were statistically nonsignificant. The data confirm that HTK and UW, with exception of biliary complications, are considered comparable in clinical liver transplantation. The same conclusion can be taken from the literature analyzed concerning renal transplantation, and in smaller groups of pancreas transplants, similar results were published.

Adenosine↗
PubMedDate not supplied

[Functional and economic impact of the use of Wisconsin University conservation solution versus Eurocollins in relation to the period of cold ischemia in renal transplantation of cadaveric donor].

Comparison of the effect of the Wisconsin University (WU) conservation solution in the graft's functional evolution and survival, and its cost-benefit relationship versus the Eurocollins (EC) solution with regard to cold ischaemia duration in a series of 142 consecutive adults renal transplantations from corpse donor, removed with beating heart. Of 142 kidneys, 92 (64.7%) were kept in WU and 50 (35.2%) in EC. Of the WU group, 62 (67.3%) kidneys were transplanted after a cold ischaemia of under 24 hours and 30 (32.6%) after cold ischaemia of more than 24 hours. In the EC group, 23 (46%) were kept in cold ischaemia for an interval shorter than or equal to 24 hours and 27 (54%) for more than 24 hours. Incidence of initial graft dysfunction (IGD) was greater in the EC groups (65% and 78%) versus the WU groups (39% and 50%), the difference being statistically significant (p). The graft function, as indicated by the creatinine levels was always better in the WU groups. There was a decreased need for complementary dialysis sessions, less days of oliguria and shorter hospitalization in the WU groups (p). There were no significant differences in the four series with regard to rejection episodes, cyclosporin-related nephrotoxicity, and vascular and urinary tract complications. All of which turn cost-effective the higher cost per litre of the WU versus the EC solution. Graft survival at 12 and 24 months was also significantly (p) higher for grafts kept in WU. This paper presents the results obtained in the analysis of our transplanted patients. In our experience, the WU solution allows better conservation of renal grafts, with less IGD and better graft survival at 12 and 24 months. These results turn cost-effective the higher cost per litre of the WU versus the EC solution.

Adenosine↗
PubMed1996

Comparison of University of Wisconsin and University of Pittsburgh solutions for heart transplantation.

The effectiveness of University of Wisconsin (UW) and University of Pittsburgh (UP) solutions for the preservation of rat hearts was compared. Lewis rat hearts were preserved with UW (group A, n = 45) or UP (group B, n = 45) solution for 0 or 24 h and then transplanted heterotopically into the recipients' abdomen. Ten recipients in each group were observed to obtain 1-week graft survival rates. Tissue water content and tissue content of adenine nucleotides were measured 2 h after transplantation in six grafts from each group. Six hearts preserved for 0 h and seven hearts preserved for 24 h were taken from each group 24 h after grafting for histopathology. The 1-week graft survival rates of groups A24 and B24 were 60% and 10%, respectively. In the 24-h preserved grafts, adenosine triphosphate (ATP) and energy charge [(ATP + adenosine diphosphate/2)/(ATP + adenosine diphosphate + adenosine monophosphate)] of groups A and B were 0.972 +/- 0.165 and 0.200 +/- 0.123 mg/g wet tissue (P < 0.05) and 74.4% and 61.1% (P < 0.05), respectively. The tissue water content of group A24 was 71.7%, whereas that of group B24 was 74.1% (P < 0.05). Histopathology revealed more severe muscle edema and necrosis and infiltration of polymorphonuclear cells in group B24 than in group A24. We conclude that UW solution is more appropriate for rat heart preservation than UP solution.

Abdomen↗
PubMed2004

Teaching the basics of clinical pharmaceutical care: innovative pharmacy workshops at the University of Wisconsin and the University of Nebraska.

BACKGROUND: Safe and effective prescription writing, using drug formularies, and managing pharmaceutical care are skills medical students need to acquire. Spurred by the Undergraduate Medical Education for the 21st Century (UME-21) grants, the University of Wisconsin and the University of Nebraska independently developed educational workshops to address these competencies. METHODS: The University of Wisconsin's workshop is presented to medical students at the start of their third year. They receive information from pharmacists on medication errors, prescription writing, and drug formularies. A "learners guide" summary is discussed by a physician, which brings into focus the clinical application of the didactic session. A small-group session follows with hands-on experience in writing prescriptions and using formularies for three patient case scenarios. The workshop at the University of Nebraska consists of three sessions during the third-year internal medicine clerkship. In the first session, pharmacists discuss formularies, the Pharmacy and Therapeutics (PT) committee, and the preparation of a drug monograph. During the second session, students develop an evidence-based drug monograph on a product or herbal. In the final session, the class functions as a mock PT committee, and after listening to the drug monographs, determines whether the product should be added to the formulary. We evaluated students' satisfaction with the workshops using Likert scales and assessed students' ability to correctly fill out a prescription form. RESULTS: Both workshops were well received. The mean rating at University of Wisconsin was 1.7 on a scale of 1 (satisfied) to 7 (dissatisfied), and at University of Nebraska it was 3.8 with 5 (outstanding) to 1 (unacceptable). At the University of Wisconsin, on a year-end skills assessment involving 148 students, 100% of the students properly filled out a prescription. Ninety-four percent received an excellent grade, 6% a pass, and no marginal or failing grades were given out. CONCLUSIONS: The workshop on pharmaceutical prescribing was rated favorably by students. After participating in the workshop, students acquired skills in prescription writing.

Clinical Clerkship↗
PubMed1994

Loss of endothelium-dependent vasodilatation and nitric oxide release after myocardial protection with University of Wisconsin solution.

University of Wisconsin solution has proved to be a superior form of cardioplegia for cardiac transplantation, demonstrating better functional recovery than that provided by extracellular crystalloid solutions. Furthermore, experimental data have suggested a role for University of Wisconsin solution in protection of the neonatal heart during operations for congenital heart defects. However, significant concerns have been raised regarding potential endothelial injury from the high potassium concentration contained in University of Wisconsin solution that could affect its safety and thus its clinical application. Fourteen neonatal (aged 1 to 3 days) piglet hearts were harvested and supported on an isolated, blood-perfused circuit. Endothelium-dependent vasodilatation was measured by bradykinin (10(-6) mol/L) infusion and nitric oxide release was determined. Endothelium-independent vasodilatation was then induced by sodium nitroprusside (10(-6) mol/L) infusion. A 2-hour period of cold cardioplegic arrest was instituted with multidose University of Wisconsin solution (group 1, n = 7) or blood cardioplegia (group 2, n = 7). After reperfusion and stabilization, another stimulation with bradykinin and nitroprusside was carried out and nitric oxide was again measured. After 2 hours of arrest with University of Wisconsin solution, there was a near-complete loss of vasodilatation in response to bradykinin infusion; coronary blood flow reached 245% of baseline before arrest versus only 117% of baseline after arrest (p = 0.0011). This correlated with an inability of the endothelium to release nitric oxide (96 +/- 30 nmol/min before arrest versus -32 +/- 9 nmol/min after arrest, p = 0.0039. In group 2, the vasodilatory response to bradykinin was preserved after arrest and reperfusion; 265% of baseline before arrest versus 222% of baseline after arrest. These results demonstrate a loss of endothelium-dependent vasodilatation after multidose University of Wisconsin cardioplegia caused by the inability of the endothelium to release nitric oxide. In contrast, blood cardioplegia does not result in impaired endothelial function.

Adenosine↗
PubMed1996

Preservation of endothelium-dependent vasodilation with low-potassium University of Wisconsin solution.

University of Wisconsin solution has provided excellent myocardial preservation. However, the high potassium content of the currently available University of Wisconsin solution has been implicated in coronary artery endothelial damage. We placed 16 neonatal (age 1 to 3 days) Duroc piglet hearts on an isolated nonworking perfusion circuit. Endothelium-dependent and endothelium-independent vasodilation were tested by measuring coronary blood flow after intracoronary infusion of bradykinin (10(-6) mol/L) and nitroprusside (10(-6) mol/L), respectively. In addition, nitric oxide levels were measured after bradykinin infusion. The hearts were then arrested blindly with either a modified University of Wisconsin solution (group 1; n = 8, K+ = 25 mEq/L) or standard University of Wisconsin solution (group 2; n = 8, K+ = 129 mEq/L) by infusion of cardioplegic solution every 20 minutes for a total of 2 hours. After bradykinin infusion, the mean coronary blood flow increased by 237.1% +/- 14.0% of baseline valves before arrest and by 232.8% +/- 16.0% after arrest in group 1 (p = not significant). As in the first group, the mean coronary blood flow in group 2 increased by 231.1% +/- 13.7% before arrest; however, the increase in mean coronary blood flow after arrest was significantly attenuated (163.3% +/- 12.8%, p < 0.01). The loss of endothelium-dependent coronary blood flow response in group 2 correlated with a decreased capacity to release nitric oxide after arrest (prearrest 8.25 +/- 2.30 nmol/min per gram versus postarrest -2.46 +/- 2.29 nmol/min per gram, p < 0.01). Endothelium-independent vasodilatory response revealed no significant difference between groups before and after arrest. These results suggest that the low-potassium University of Wisconsin solution provides superior protection of the endothelium by preserving the endothelium-dependent vasodilatory response to nitric oxide release.

Adenosine↗
PubMed1991

Comparative ultrastructural study of rat livers preserved in Euro-Collins or University of Wisconsin solution.

University of Wisconsin solution greatly lengthens the time liver storage is possible compared with all previous solutions used. To test whether this improvement is related to better preservation of the endothelial cell, which is thought to be the most vulnerable cell type in cold storage, we compared time-related ultrastructural changes in rat livers stored in this solution or in Euro-Collins solution. Rat livers were harvested after combined arterial and portal perfusion with the cold-storage solution. They were then preserved for different lengths of time in the same solution at 4 degrees C before being perfusion-fixed and processed for light and electron microscopy. The first preservation damage was noted in endothelial cells; the time course of the lesions was similar in both solutions. After 2 hr of storage, enlarged and ruptured fenestrae with many gaps were observed. Swollen at 4 hr, the endothelial cells became stringlike at 10 hr, leading to stripped sinusoidal walls. Hepatocytes appeared better preserved in University of Wisconsin solution. The amount of glycogen, maintained near the control level at 24 hr in the latter, decreased dramatically between 0 and 4 hr in Euro-Collins solution, as ultrastructurally observed and biochemically confirmed. Furthermore, sinusoidal obstruction by blebs originating from the hepatocytes and quantified by image analysis on electron micrographs was markedly delayed. It was significantly less pronounced in University of Wisconsin solution at 24 hr than in Euro-Collins solution at 2 hr (p less than or equal to 0.05). Our findings confirm that endothelial cells are highly susceptible to preservation damage and show that University of Wisconsin solution does not improve preservation during storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1993

Human islet isolation--a prospective randomized comparison of pancreatic vascular perfusion with hyperosmolar citrate or University of Wisconsin solution.

University of Wisconsin solution has become the most commonly used vascular perfusate during multiorgan donation world-wide. In the UK however, hyperosmolar citrate remains in common use. The purpose of this prospective randomized study was to compare the effect of systemic perfusion with UW or HOC on subsequent islet yield and purification for pancreata with short cold ischemic times. Seven pancreata were randomized to each group, with the donor age, pancreas weight, and period of cold ischemia being similar in both. Perfusion with UW was shown to inhibit collagenase digestion, and a higher concentration of this enzyme was needed to achieve comparable numbers of islets with good separation of exocrine and islet tissue after a similar period of digestion. There were no differences in the number, size, purity, or viability of islets between the two groups. In conclusion, UW solution offers no benefits over HOC for pancreata with short cold ischemic times, and because of its expense and need to use greater amounts of collagenase enzyme, we continue to use HOC.

Adenosine↗
PubMed1993

Six-hour preservation of the isolated working rat heart improved with University of Wisconsin solution.

University of Wisconsin (UW) solution was compared with modified St. Thomas cardioplegic solution for 6-hour preservation of isolated working rat hearts. The hearts (9 in each group) were arrested with the respective solution and stored, still cannulated, for 6 hours at 4 degrees C. After retrograde reperfusion for 30 minutes, antegrade perfusion was begun at constant left atrial and aortic pressures. Following 25 minutes of antegrade perfusion the hemodynamic recovery of the UW-preserved hearts was superior to that of the other hearts (cardiac output 46.0 +/- 4.8% of the preischemic control values in the UW group and 10.0 +/- 6.0% in the St. Thomas group, p < 0.01). The adenosine triphosphate content was significantly higher in the UW-preserved hearts (18.8 +/- 0.9 vs. 14.7 +/- 1.6 mumol/g dry weight, p < 0.05). No significant intergroup difference was found in aspartate aminotransferase leak or tissue glycogen. The study demonstrated both better function and enhancement of high-energy phosphates with UW solution vs. modified St. Thomas solution in isolated rat hearts, although without difference in enzyme leakage or tissue glycogen, after 6-hour preservation.

Adenosine↗
PubMed1998

Impaired endothelium-derived hyperpolarizing factor-mediated relaxation in coronary arteries by cold storage with University of Wisconsin solution.

OBJECTIVES: University of Wisconsin solution is widely used to preserve organs for transplantation, but its effect on the individual endothelium-derived relaxing factors has not been studied. This study was designed to examine the effect of cold storage of the heart with University of Wisconsin solution on relaxation mediated by the endothelium-derived hyperpolarizing factor (EDHF). METHODS: Porcine coronary artery rings were studied in organ chambers. Relaxation in response to the EDHFs stimuli bradykinin and A23187 in U46619 (30 nmol/L)-induced precontraction after incubation with University of Wisconsin solution (either at 37 degrees C in the oxygenated organ chamber or at 4 degrees C in a refrigerator for 4 hours) was compared with the control. RESULTS: During the incubation, the coronary tone initially increased transiently (4.8 +/- 0.8 gm) and was subsequently reduced by 10.9 +/- 1.2 gm. Under both normothermia and hypothermia, after the incubation, the relaxation mediated by EDHF significantly decreased (under normothermia: from 68.7% +/- 10.2% to 32.1% +/- 8%, n = 7, p = 0.001, for bradykinin and from 79.9% +/- 8.4% to 56.9% +/- 8.5%, n = 7, p = 0.01, for A23187; under hypothermia and hypoxia: to 18.9% +/- 5.6%, n = 9, p = 0.0005, for bradykinin and 52.7% +/- 7.5%, n = 9, p = 0.03, for A23187). The incubation at normothermia also impaired the coronary smooth muscle contractility to U46619, but this contractility was preserved by cold storage. CONCLUSIONS: During cold storage, University of Wisconsin solution impairs the endothelium-dependent relaxation mediated by EDHF in the coronary circulation. This effect exists after the storage for at least 1 hour.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Assessment of function, perfusion, metabolism, and histology in hearts preserved with University of Wisconsin solution.

BACKGROUND: University of Wisconsin solution has shown promise for prolonged cardiac preservation. This study compared the effects of 24-hour cold storage and perfusion preservation techniques by assessment of function, perfusion, metabolism, and histological changes. METHODS AND RESULTS: Three groups of rabbit hearts (n = 6 each) were evaluated: 1) control with immediate reperfusion, 2) continuous perfusion preservation, and 3) cold storage. Hearts were reperfused for 30 minutes, and left ventricular systolic pressure (LVSP) was measured by isovolumetric balloon (LVEDP, 20 mm Hg). We used 201Tl to assess perfusion and 14C-acetate to assess metabolism by macroautoradiography. LVSP was similar for controls and hearts preserved with continuous perfusion (134.8 +/- 2.1 versus 112.2 +/- 6.0 mm Hg, respectively). Hearts preserved with cold storage techniques were significantly worse (36.7 +/- 6.0 versus 134.4 +/- 8.2 mm Hg, p < 0.001). Controls showed homogeneous perfusion and metabolism, whereas hearts in the continuous perfusion group showed mild hypoperfusion and histological damage (26.4 +/- 2.7% of left ventricular cross section). Hearts in the cold storage group had 51.7 +/- 1.2% of the left ventricle hypoperfused and damaged. Histology in the control group was normal; in the perfused group, there were only mild changes; and in the cold storage group, there were extensive derangements of cellular architecture. CONCLUSIONS: Continuous perfusion of the heart with 4 degrees C modified University of Wisconsin solution provided function comparable to that of control. Conversely, cold storage showed extremely poor return of function. Autoradiography confirmed mild perfusion and metabolism abnormalities in control and continuous perfusion hearts, whereas there was marked derangement of cellular architecture, perfusion, and metabolism in the cold storage hearts.

Adenosine↗
PubMed2001

Protection of the rat liver against rewarming ischemic injury by University of Wisconsin solution.

BACKGROUND/AIM: University of Wisconsin (UW) solution has been proven able to prevent liver injury during cold ischemia. During rewarming ischemia, however, the efficacy of this solution in preserving hepatocyte function is unclear. The aim of the present study was to investigate to what extent UW solution protects rat liver during rewarming ischemia. METHODS: Livers were washed out with cool physiologic saline or with UW solution and subjected to rewarming ischemia for periods of 20 min or 45 min followed by reperfusion using a blood-free perfusion model. RESULTS: In comparison with controls, ischemia for 20 min in saline-treated livers led to mild depression of hepatocyte function, while UW solution afforded complete protection of the liver. In UW-treated livers, compared with saline-treated livers exposed to ischemia for 45 min, portal flow was slightly but significantly higher, bile production was increased by 62%, and lactate dehydrogenase leakage into the perfusate was reduced by 61%. In an attempt to explain mechanisms of liver protection by UW solution, we found that UW solution inhibited conversion of hypoxanthine into uric acid, but this effect was not associated with decreased degradation of adenine nucleotides in the liver during ischemia. Following 30 min reperfusion, UW solution increased tissue levels of adenosine triphosphate (not significantly) and adenosine diphosphate (significantly). Further, UW solution markedly reduced tumor necrosis factor-alpha release by the liver both after ischemia and after reperfusion. CONCLUSIONS: These results create the hypothesis that UW solution may protect liver tissue during ischemia in liver surgery as well as during the implantation stage of liver transplantation.

Adenosine↗
PubMed2003

Functional and structural integrity of porcine pancreatic grafts subjected to a period of warm ischemia and cold preservation with histidine-tryptophan-ketoglutarate (custodiol) or University of Wisconsin solution.

BACKGROUND: University of Wisconsin (UW) solution (Viaspan) is currently used to preserve organs from nonheartbeating donors. Histidine-tryptophan-ketoglutarate (HTK) solution (Custodiol) is of proven efficacy in experimental pancreas preservation, but its efficacy in combined warm ischemia (WI) and cold ischemia (CI) is unknown. The viability of HTK-preserved porcine pancreatic grafts was assessed after various periods of WI and compared with grafts flushed and preserved with UW solution. METHODS: A total of 14 pigs were used: G1 (n=4, UW) and G2 (n=4, HTK) with 15-min WI and 16-hr cold storage; G3 (n=3, UW) and G4 (n=3, HTK) with 30-min WI and 16-hr cold storage. RESULTS: All animals in G1 and G2 were normoglycemic, whereas only 66% of pancreases were functioning in G3 and G4. HTK perfusion was associated with increased wet weight. Transient hyperinsulinemia was noted in all the groups on postoperative day 1 (mean range: 8.9-12.4 microU/L). Postoperative serum amylase and lipase were more pronounced in G3 and G4. However, HTK-stored grafts exhibited less evidence of biochemical pancreatitis as compared with UW-stored grafts on the first postoperative day in the group with 15-min WI. Mean K values of intravenous glucose tolerance tests on postoperative day 14 were similar in both groups. Vascular congestion was uniformly observed and was considered a typical feature of WI. CONCLUSIONS: Porcine pancreatic grafts are viable after 16-hr CI following 15-min WI in this experimental nonheartbeating donor model. HTK solution seems to provide reliable graft function in this setting and to be equivalent to UW.

Adenosine↗
PubMed1991

[Preservation of donor livers with University of Wisconsin solution].

The University of Wisconsin-solution extends the cold storage time of liver grafts over 20 hours. The early function is equal or better than with Eurocollins solution. Due to the extended preservation time, logistical advantages are present. However, deliberate extension of cold ischemia over the limit of 20 to 24 hours seems not yet indicated, since primary non-functioning grafts have a higher incidence after extended preservation.

Adenosine↗
PubMed1996

Catalytic metal ions and the loss of reduced glutathione from University of Wisconsin preservation solution.

The University of Wisconsin solution is widely used for organ preservation. We show that this fluid is often contaminated by traces of iron catalytic for free radical reactions, as demonstrated by the bleomycin assay and the ability of the iron to stimulate lipid peroxidation. Reduced glutathione (GSH) added to University of Wisconsin solution during its commercial preparation had oxidized to the disulfide in all samples examined. Addition of GSH to UW solution showed its half-life to be about one day. The metal ion chelators desferrioxamine and phenanthroline did not substantially delay the loss of GSH, although desferrioxamine was able to suppress iron-mediated lipid peroxidation induced by the contaminant iron in the preservation solution. Additional iron was released from rat liver after a period of cold storage/rewarming.

Adenosine↗