Comparative evaluation of two perfusion solutions for liver preservation and transplantation

The University of Wisconsin solution (UW) and the Bretschneider solution (HTK) were used in 39 adult cadaveric donors: 22 perfused with UW (group 1) and 17 with HTK (group II). Donors were flushed through the aorta (UW, 5 to 6 L; HTK, 8 to 10 L) and through the portal vein (UW or HTK, 1 L). Grafts perfused with HTK showed lower levels of SGOT at postoperative day 7 than those transplanted with UW (38 +/- 19 vs 58 +/- 31, P < .05). No difference was observed in other functional and outcome parameters. No cases of primary dysfunction were observed. Six-month graft survival was 85.7% in HTK group and 80.9% in UW group (P = NS). Six unrelated deaths were observed. Five biliary complications were observed in five patients: three in the UW group and two in the HTK group. In conclusion, data fail to show major differences between the two solutions used.     

二种不同成份灌洗液肺保存效果的对比

目的 比较2种不同成份肺灌洗液的肺保存效果.方法 将犬分成2组,一组供肺采用改良的Euro-Collins液(含高钾,钾浓度108mmol/L)灌洗,另一组用低钾葡萄糖液(LPG液,钾浓度4 mmol/L)灌洗.4℃保存6小时后行异体左肺移植,保留受体的右肺.术后10分钟～72小时定时阻断右肺动脉血流,采股动脉血作血液气体分析,并作病理检查.结果 改良的Euro-Collins液和LPG液灌洗的肺移植后即刻受体动脉血氧分压(PaO2)分别为(17.3±6.2)kPa和(19.7±7.0)kPa.CO2分压(PaCO2)分别为(5.28±1.17)kPa和(4.8±0.7)kPa,两组比较,P>0.05,移植后72小时的PaO2分别为(14.6±6.1)kPa和(18.4±7.6)kPa,PaCO2分别为(4.2±0.9)kPa和(4.6±0.7)kPa,两组比较,P>0.05.移植肺组织光镜和电镜观察发现,灌洗后即刻及保存6小时的组织学改变主要表现为肺泡上皮及毛细血管上皮细胞肿胀、肥大、变性,移植后72小时可见肺泡内有渗出、淋巴细胞浸润及血管壁增厚,2个组的病理改变相似.结论 含高钾的改良Euro-Collins液及含低钾的LPG液肺保存效果相似,灌洗液中的K+浓度并非影响移植肺功能的关键因素.     

A pathophysiologic study of the kidney tubule to optimize organ preservation solutions

BACKGROUND: Tissue damage at the time of organ transplantation has a negative impact on the subsequent success of the procedure, both in the immediate and longer term. Hypothermia is the principal element used to prolong organ viability ex vivo, but paradoxically also induces cellular edema through inhibition of energy-dependent adenosine triphosphatases (ATPases). This induces an electrolyte imbalance that leads to fluid influx and cell swelling. It is important, therefore, that improvements are made in the preservation of ischemic organs to reduce this injury. METHODS: This study has applied a novel in vitro system to model cold and warm ischemic-induced renal tubule swelling that characterizes tissue damage in ischemia/reperfusion injury. Biochemical blockade of ATPases in this system using strophanthidin modeled the effects of energy depletion and induced cell swelling. By measuring such tubule swelling and changes to tubular cell volume in isolated rabbit renal proximal tubules, an analysis was made that defined the basis on which an optimal preservation solution may be developed. RESULTS: The data show that our model could reproduce ischemically induced cell swelling and characterized the response at the cellular level of tubules to different components of preservation solutions. The data indicate that an isosmolar, phosphate-buffered, sucrose solution prevented tubule swelling more effectively than Euro-Collins, hyperosmolar citrate, or University of Wisconsin solutions that are in routine clinical use. CONCLUSION: Future developments in organ preservation may significantly improve transplant outcomes. Our novel analysis forms the basis of future whole-organ studies that ultimately may allow us to propose an optimum platform for improved preservation solutions.     

A comparative study of the most widely used solutions for cardiac graft preservation during hypothermia.

BACKGROUND: Reports conflict on the benefits of preservative solutions. We investigated the efficacy of the most widely used cardioplegic solutions by comparing extracellular solutions such as Celsior solution, St. Thomas Hospital solutions 1 and 2 (STH-1, STH-2), the modified University of Wisconsin solution (UW-1), Lyon Preservation solution (LYPS) from our laboratory, and intracellular solutions such as standard University of Wisconsin solution (UW), Bretschneider solution (HTK), Stanford solution (STF), and Euro-Collins solution (EC). METHODS: Male rats (n = 110) were randomized into 11 groups: LYPS, Celsior, STH-1, STH-2, UW-1, UW, HTK, STF, EC, and normal saline solution groups, and a control group. All hearts, except controls, were preserved by cold storage (8 hours at 4 degrees C) in the various solutions. We used an isolated non-working-heart model and biopsy specimens to assess heart preservation (n = 5/group). RESULTS: Hearts stored in the EC and saline solutions had poor left ventricular developed pressure (LVDP) x heart rate (HR) (1,407.5 +/- 154 and 1,390 +/- 439 mm Hg/mn, respectively). In contrast, hearts stored in LYPS and Celsior had a LVDP x HR close to control hearts (31,349 +/- 1,847, 27,620 +/- 1,207, and 36,627 +/- 1,322 mm Hg/mn, respectively), whereas hearts stored in STH-1, STH-2, UW-1, UW, HTK, and STF had intermediate functional response (14,278 +/- 2,176, 12,402 +/- 1,571, 11,428 +/- 1,629, 11,603 +/- 2,521, 7,045 +/- 537, and 7,086 +/- 1,206 mm Hg/mn, respectively). Hearts preserved with STH-2, UW, HTK, STF, EC, and saline solution showed significantly increased release of creatine kinase and lactate dehydrogenase than did control hearts or hearts preserved in Celsior, LYPS, STH-1, and UW-1. The energetic charge (EC = [(0.5 adenosine diphosphate + adenosine triphosphate) / (adenosine triphosphate + adenosine diphosphate + adenosine monophosphate)]) in STH-2, UW, HTK, STF, EC, and saline groups was significantly lower (p < 0.05) than in the other groups. CONCLUSION: Extracellular-type solutions provided better preservation than did intracellular-type solutions. However, UW and UW-1 (intracellular- and extracellular-type solutions) provided equivalent preservation of cardiac function. Preservation quality may be attributed to calcium, often added to extracellular solutions. Among extracellular solutions, Celsior and LYPS solution showed comparable efficacy on left ventricular function and seemed to offer better preservation than the other solutions tested in this study.     

Wisconsin and Celsior solutions in renal preservation: a comparative preliminary study

The aim of this study was to evaluate the efficacy of the Celsior (C) solution for flushing and cold storage of cadaveric renal allografts. Among 177 cadaveric renal allografts harvested and transplanted in our unit, 138 were preserved with the University of Wisconsin (W) solution and 39 with the C solution. The mean age of the recipients was 48.1 +/- 13.5 years, including 107 men and 70 women. The immunosuppressive regimens were tacrolimus-based (n = 118) or cyclosporine-based (n = 59). Grafts perfused with W solution were obtained from older donors than those perfused with C solution (42.3 +/- 16.9 vs 38.1 +/- 12.5 years; P = .017) and had been transplanted to older recipients (49.5 +/- 14.4 vs 43.3 +/- 13.0 years; P = .017). The prevalence of delayed graft function (DGF) was similar in the 2 groups (39.1% in the W group vs 23.7% in the C group; P = .097), as well as the incidence of primary nonfunction grafts (5.8% vs 2.7%; P = .427). The serum creatinine value at 1 month was significantly higher among grafts preserved with W versus solution (1.9 +/- 0.9 vs 1.5 +/- 0.5 mg/dL; P = .000) as well as at 12 months (1.63 +/- 0.5 vs 1.35 +/- 0.4 mg/dL; P = .003). There were no differences in graft survival at 12 months (97% C group vs 88% W group; P = .069). Our results showed that C solution was equivalent to W solution with respect to DGF and primary function of kidneys. The differences in renal function may have been due to differences in donor and recipient ages.     

Efficacy of renal preservation: comparative study of Celsior and University of Wisconsin solutions

OBJECTIVE: We sought to compare the efficacy of Celsior and University of Wisconsin (UW) solutions on the perfusion and cold storage of renal grafts for human transplantation. PATIENTS AND METHODS: Retrospective analyses of 313 kidney transplants were performed between 2002 and 2005; group A (n = 160), UW solution and group B (n = 153), Celsior solution were used in the preservation of the organs. The mean donor age was lower in group B (group A = 42.67 years vs group B = 38.96 years; P < .05), living donors were more frequent in the UW group (group A = 10% vs group B = 0.9%; P < .001). Multiorgan procurement procedures were more common in the Celsior group (group A = 75% vs group B = 81.7%; P < .001). Recipients with no associated comorbidities were more frequent in the UW group (group A = 50% vs group B = 36%; P < .001). Recipient mean age, cold ischemia time, and HLA matches were comparable. RESULTS: Delayed graft function (group A = 22.7% vs group B = 20.6%), acute rejections (group A = 21.4% vs group B = 18.4%), and serum creatinine at 6 months (group A = 1.75 vs group B = 1.67 mg/dL), 1 year (group A = 1.47 vs group B = 1.74 mg/dL), and 2 years (group A = 1.43 vs group B = 1.58 mg/dL) showed no differences (P = NS). Graft (group A = 82.23% vs group B = 84.11%) and patient (group A = 93% vs group B = 93.69%) survivals at 3 years were similar (P = NS). There were no differences in the causes of graft loss. CONCLUSION: The efficacy of UW and Celsior solutions is equivalent in the cold storage and renal preservation for transplantation.     

A randomized prospective trial of cold storage versus pulsatile perfusion for cadaver kidney preservation

In a randomized trial conducted in 9 Ontario transplant centers, 107 cadaver kidney donors were randomized so that both kidneys were preserved either by simple cold storage (CS) or by pulsatile perfusion (PP). After exclusions and losses to follow-up, there were 90 patients in the CS group and 91 in the PP group. Total preservation times were similar in the two groups (27.7 +/- 12 and 30.5 +/- 10 hr), as was the proportion of kidneys with long (greater than 36 hr) storage times (21% and 26%). Twelve-month graft survival was 70% for CS and 75% for PP (not significant, NS); patient survival was 89% for CS and 95% for PP (NS). The incidence of kidneys that never functioned was also similar in the two groups (14% vs. 15%, respectively). However, the risk of early, reversible graft dysfunction was significantly higher for CS (44%) than for PP (31%). The same effect was observed with two independent methods of assessment of graft function. The chief effect of PP on renal function was in reduction of the mean serum creatinine at 1 week (632 mumol/L for CS vs. 403 mumol/L for PP, P less than .001). There was no significant influence of storage mode on the rapidity of urine output or number of dialyses required. No apparent effect of cyclosporine on the results with either preservation method was seen. We conclude that the case for retention of PP for kidney preservation now rests on its ability to achieve slightly better initial function than CS. However, the mild dysfunction observed with CS did not appear to translate into long-term detriment. When these considerations are weighed against the increased cost of PP, the advantage may lie with cold storage.     

A preliminary report of the HTK randomized multicenter study comparing kidney graft preservation with HTK and EuroCollins solutions

The main goal of transplantation is to restore good renal function and to improve the quality of life of thousands of dialysis patients, something which can only be achieved by providing them with well functioning grafts. Delayed renal allograft function is a serious problem. It is important to prevent this complication because it makes the diagnosis of acute rejection in the early postoperative period difficult, increases the necessity for diagnostic procedures, introduces dialysis treatments and prolongs hospital stay. The aetiology of delayed graft function (DGF) is multifactorial, and factors including donor management, technique used for organ procurement and preservation, age, anatomical variations in the graft, ischemia periods, use of cyclosporine A (CyA) or recipient immunological reactions have been implicated. Using different preservation solutions DGF rates vary from 30% to 60%. Recent clinical data have demonstrated better preservation and improved renal function posttransplant with HTK and University of Wisconsin (UW) solutions compared to EuroCollins solution. In a randomized multicenter study in collaboration with the Eurotransplant organ exchange organization, the efficacy of the HTK solution in renal transplantation was compared to EuroCollins and UW solutions in two parallel prospective randomized trials. The first preliminary results comparing HTK and EuroCollins solutions are reported here.     

A multicenter pilot prospective study comparing Celsior and University of Wisconsin preserving solutions for use in liver transplantation

Primary dysfunction (PDF) still occurs after orthotopic liver transplantation (OLT). Celsior solution (CS) might offer some advantages over the conventional University of Wisconsin (UW) solution for organ preservation, but to date, this has not been prospectively evaluated in the context of OLT. In this prospective, randomized, multicenter, pilot study, 215 potential liver donors were enrolled and randomized. In 42 cases, the livers were unsuitable for transplantation; therefore, 173 randomized livers ultimately were implanted after perfusion and cold preservation with CS (n = 83) or UW solution (n = 90). In accord with the indications of the CS manufacturing company, total CS infusion volume was 90 mL/kg, greater than that of UW solution (60 mL/kg). The main aim of the study is to compare the prevalence of PDF between the two groups. Donor and recipient variables were similar in the two groups. Episodes of PDF were numerically lower in the CS (2.4%) than UW group (7.8%), but the difference was not statistically significant. There was a trend toward a lesser need for early re-OLT (<30 days) in the CS group (P = .0507), but again, no statistically significant difference emerged. Overall and time-differentiated postoperative deaths also were similar. One-year actuarial patient (UW, 89% v CS, 87%) and graft (UW, 83% v CS, 85%) survival rates were similar. In conclusion, CS was similar to UW solution as a preservation solution in the clinical setting of OLT at the infusion volumes described, although some theoretical advantages of CS composition suggest that CS might prove a valid alternative to UW preservation solution in multiorgan harvesting, including the liver. A study on a larger patient basis is needed. (Liver Transpl 2003;9:814-821.)     

A comparison of Collins and UW solutions for cold ischemic preservation of the rat liver

A new solution which can extend successful preservation times for hepatic allografts was recently developed at the University of Wisconsin (UW). To examine the mechanism of improved viability using this solution, we developed a model of orthotopic hepatic transplantation in the rat. As a baseline study, we compared parameters of viability of allografts preserved in Collins solution to those preserved in UW, including survival, bile output, peak AST, and allograft weight change during storage. Seventy-four rats were transplanted following storage in Collins solution and 70 rats were transplanted after storage in UW. Cold-storage time varied between 2 and 24 hr. The survival with preservation in UW was significantly better than that with Collins when storage time was greater than 2 hr. The preservation time for a viable organ using UW was greater than double that using Collins. The peak AST using UW was lower than that with Collins for cold ischemic times (CIT) up to 10 hr, with significance demonstrated at 5-6 and 7-8 hr when compared with Collins. Prolonged CIT resulted in an increase in liver weight with Collins-preserved livers and a decrease in weight with UW-preserved livers. Using a model of orthotopic liver transplantation in the rat, we demonstrated a doubling of preservation time when UW solution was substituted for Collins. Similar improvements in recipient survival and biochemical parameters of injury have been demonstrated in the canine model and in human clinical trials.     

A comparative study of experimental models for cardiac preservation through orthotopic transplantation

Various kinds of models for canine heart preservation were evaluated through orthotopic transplantation. Following warm ischemic (WIT) and preservation times (PT), donor hearts were orthotopically transplanted to recipients and observed for 2 hours. The study was divided into four groups. A heart-lung preparation (Group A) was preserved by coronary perfusion with diluted blood for an hour following 15-minute WIT in A-1 (n = 33), and 2 hours following 30-minute WIT in A-2 (n = 19). Following 30-minute WIT, the heart (Group B) was preserved for an hour by coronary perfusion with diluted blood in B-1 (n = 20), a modified Krebs solution in B-2 (n = 14), and a EL-solution in B-2 (n = 14). Following 30-minute WIT, the heart (Group C) was preserved for 2 hours by a Langendorff's model with coronary perfusion using perfluorochemical in C-1 (n = 5) and Hydroxyethyl starch in C-2 (n = 1). In Group D, electromechanical arrest of the heart and coronary vascular washout were performed in D-1 (n = 8) with K+ cardioplegia, D-2 (n = 8) with K+-verapamil cardioplegia, and D-3 (n = 5) with Collins M-verapamil cardioplegia. The heart was then removed and suspended in the same solution. The graft was preserved at 4 degrees C for 6 hours in D-1 and D-2, and 24 hours in D-3. Fourty-eight % in A-1 and 26% in A-2 were successfully transplanted.(ABSTRACT TRUNCATED AT 250 WORDS)