Single-donor cold storage versus machine perfusion in cadaver kidney preservation

Preservation of thirty-eight consecutive renal allograft donors was studied in a prospective, randomized protocol. Procurement was in-situ cooled, en-bloc nephrectomy accomplished by a single program. Nine pairs were deleted because of nonutilization of one kidney or change in mode of preservation. The remaining twenty nine pairs were implanted by twenty two institutions through usual organ sharing policies. Results showed that posttransplantation dialysis was required in 17% of machine-perfused and 63% of cold-stored allografts, which reached statistical significance (P less than 0.01). This increased number of dialyses in patients receiving the cold-stored kidneys offsets cost savings achieved through transporting cold stored allografts. This study shows machine-perfused renal allografts to be superior to paired, cold-stored allografts when analyzed with respect to early graft function.     

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.     

Influence of acute tubular necrosis on first cadaver kidney transplant function

Prolonged cold storage following intracellular electrolyte flushing increases the probability of significant acute tubular necrosis after cadaver kidney transplantation. The renal function of primary cadaver kidney grafts was compared in 68 recipients who required dialysis and 92 who did not require dialysis during the first week after transplantation. All kidneys were retrieved from beating-heart cadaver donors by our center, flushed with ice-cold intracellular electrolyte solution and cold-stored until transplantation at our hospital. Recipients requiring dialysis during the first week after transplantation received kidneys with a significantly longer cold storage time (27.4 plus or minus 10.2 versus 23.2 plus or minus 7.6 hours) and had significantly higher 1-month serum creatinine nadirs (2.1 plus or minus 1.3 versus 1.5 plus or minus 0.6 mg./dl.). Actuarial kidney graft survivals and serum creatinine levels 1 to 5 years after grafting were not significantly different. Acute tubular necrosis following primary cadaver kidney transplantation does not adversely affect long-term function of kidney grafts flushed with intracellular electrolyte solution and cold-stored until transplantation.     

The Cost-Effectiveness of Organ Preservation Methods in Renal Transplantation: US Projections Based on the Machine Preservation Trial

Introduction

The European Machine Preservation Trial (MPT) found a significantly lower rate of delayed graft function and improved graft survival in machine-perfused kidneys compared to cold-stored kidneys in the first year following kidney transplantation. Little is known about the cost-effectiveness of various organ preservation methods.

Methods

Outcome data from the MPT have been used to conduct a comparative cost-effectiveness analysis based on preservation method for both standard criteria (SCD) and expanded criteria donor (ECD) kidney transplants in the United States. Using graft survival as the primary outcome measure, a cost-effectiveness model was developed using Medicare and private payer cost/payment data, as well as clinical transition probabilities based on the MPT and other studies.

Results

At 1-year posttransplant, machine perfusion is a more cost-effective option than cold storage for organ preservation in transplants involving either SCD ($92,561 vs $104,118) or ECD ($106,012 vs $114,530) kidneys. Moreover, the cost-effectiveness ratios for transplants involving machine-perfused ECD kidneys ($106,012) are similar to those for transplants using cold-stored SCD kidneys ($104,118).

Conclusion

Machine perfusion is preferable to cold storage for organ preservation in both SCD and ECD donor kidney transplants. Not only is it more cost-effective, but from all relevant perspectives it adds substantial value.     

Comparison of histidine-tryptophan ketoglutarate and University of Wisconsin solutions as primary preservation in renal allografts undergoing pulsatile perfusion

INTRODUCTION: University of Wisconsin (UW) solution is the standard preservation solution for organ transplantation. Histidine-tryptophan ketogluatarate (HTK) solution has been used increasingly for kidney, pancreas, and liver transplantation. This study compared HTK and UW used during kidney procurement with subsequent pulsatile perfusion. METHODS: Between January and October 2003, 91 deceased renal and simultaneous kidney pancreas transplants were performed (UW, n = 41, and HTK, n = 50). There were no differences with regard to donor and recipient demographics or cold ischemia. RESULTS: Delayed graft function occurred in 3 (7%) of UW and 4 (8%) of HTK-preserved kidneys (P = NS). There were no significant differences between patient or graft survival. There was an anticipated difference between total preservative volumes used (HTK: 4.1 +/- 1.0 vs UW: 3.0 +/- 0.5; P < .005). CONCLUSION: UW and HTK appear to have similar efficacy in kidney preservation with pulsatile perfusion. HTK preservation solution can be used safely in conjunction with pulsatile preservation for cold storage of renal allografts.     

Prolonged human kidney preservation by intracellular electrolyte flush followed by cold storage

No kidney transplant center responding to a kidney preservation questionnaire would accept a kidney flushed with an intracellular electrolyte solution and cold-stored for over 40 hours. This study from one center is a comparison of 50 primary cadaver kidney grafts preserved with an intracellular electrolyte flush followed by cold storage for 40 to 61 hours to 82 primary cadaver kidney grafts preserved by the same method for 9 to 24 hours. Kidneys cold-stored for over 40 hours had a significantly increased requirement for dialysis in the 1st week following transplantation (82% versus 34%) and a significantly increased 1-month serum creatinine nadir (2.3 mg/dL versus 1.7 mg/dL). Actuarial graft survivals and serum creatinine levels at 1, 2, and 3 years after grafting were not significantly different. Cadaver donor methylprednisolone (30 to 60 mg/kg) two to nine hours prior to kidney removal significantly reduced the requirement for 1st-week hemodialysis in the kidneys cold-stored for over 40 hours (60% versus 91%). Kidneys preserved by flushing with cold intracellular electrolyte solution can be successfully transplanted after over 40 hours of simple cold storage when the warm ischemia time is very short.     

Kidney transplantation from elderly donors: a prospective randomized study comparing celsior and UW solutions

AIM: The aim of present study was to assess the effect of Celsior as compared with University of Wisconsin (UW) solution on immediate and long-term function of kidney transplants harvested from elderly donors. METHODS: A prospective multicenter randomized study was designed to evaluate the efficacy of Celsior versus UW solution for the clinical preservation of the kidney. Fifty renal transplants were performed from donors over 60 years old. Twenty-five kidneys were stored in Celsior and 25 in UW solution. The groups were comparable with regard to donor and recipient characteristics. Renal function outcomes were compared by evaluating delayed graft function rates, daily urinary output, as well as the evolution of mean serum creatinine at 1, 3, 5, 7, and 15 days. RESULTS: The warm ischemia time was 42.4 +/- 11 minutes among Celsior vs 46.9 +/- 17.9 minutes in the UW cohort (P = NS). The cold ischemia time was 18 +/- 4.5 hours in Celsior and 19 +/- 6.5 hours in UW (P = NS). Delayed graft function occurred in 48% of the Celsior group and in 52% of the UW group (P = NS). Mean serum creatinine levels and mean daily urinary output were also similar. One- and 5-year graft survivals of kidneys preserved with Celsior were 91.8% and 79.3% compared with 96% and 87.4% for UW without any significant statistical difference. CONCLUSIONS: Our data show that the preservation of kidneys from elderly donors in Celsior solution is equivalent to that of UW solution.     

Improved immediate function of renal allografts with Belzer perfusate

The characteristics of 254 cadaveric kidneys were evaluated and the incidence of immediate function identified. The Belzer perfusate was used primarily (n = 140) and secondarily (n = 14) in combination with pulsatile machine perfusion. These two groups were compared with a previous group of kidneys machine-perfused with silica gel (cryoprecipitated human plasma). The incidence of immediate function of the group primarily perfused with Belzer perfusate was statistically significantly improved over that of the silica gel. The secondarily perfused Belzer group, "imported" kidneys previously preserved with simple cold storage, had notably longer periods of preservation and higher resistances on the machine. However, 100% of this group functioned immediately. Other findings in this study show that the Belzer perfusate allows for improved parenchymal function posttransplant, as noted by a more rapid clearance of serum creatinine posttransplant. When comparing the immediate function group with those suffering early dysfunction, there is a statistically significant increased resistance on the machine in the latter group. This allows for prediction of immediate function based on perfusion characteristics of the kidney. The Belzer perfusate, composed of metabolic substrates for high-energy phosphate production, improves the incidence of immediate function in machine-perfused kidneys, as well as improved qualitative function posttransplant. It also is effective as a "rescue" mechanism in previously simple cold-stored (ATP-depleted) kidneys.     

Human kidney preservation by flushing with intracellular solution and cold storage.

Simple flushing and cold storage of human kidneys for transplantation has not been accepted for preservation times exceeding 24 hours. A prospective study of 25 primary cadaver kidney transplants was performed to evaluate Collins C2 solution for human kidney preservation. Cold storage time was 10 to 23 hours in 14 cases and 26 to 44.5 hours in 11 cases. Seventeen (68%) of the kidneys had immediate, sustained function. The one-month function rate was 88%. There were no significant differences between the 10- to 23-hour and the 26- to 44.5-hour groups with respect to the incidence of first-week dialysis, one-month graft function, or mean lowest serum creatinine value. Human kidney preservation time can be safely extended beyond 24 hours with Collins C2 flushing followed by simple cold storage.     

Pretransplant assessment of renal viability by phosphorus-31 magnetic resonance spectroscopy. Clinical experience in 40 recipient patients

A group of 40 cadaveric kidneys was studied just prior to planned transplantation to further assess the applicability of 31P-MRS in the analysis of clinical renal transplant viability. Renal intracellular high-energy phosphorus metabolites (ATP [or NADP], phosphomonoester [PME] and inorganic phosphate [Pi]) and pH were measured noninvasively with MRS surface coils external to cold storage containers. Pretransplant MRS parameters were correlated with subsequent renal function in recipient patients (measured one week postoperatively by the need of dialysis, drop in serum creatinine, urine output, and 123I or 131I Hippuran assessed renal tubular function). ATP and NADP was detected in eleven kidneys and was significantly (P less than 0.001) associated with the best renal function posttransplantation. These kidneys also had the highest PME/Pi ratios (1.66-0.54), while lower ratios (0.36-0.10) were associated with prolonged acute tubular necrosis. The PME/Pi ratios significantly (P less than 0.0001) correlated with subsequent clinical renal function, whereas cold storage times (37 +/- 10 hr) or intracellular renal pH (6.53-7.91) did not. These preliminary data suggest that MRS is a noninvasive, nondestructive and sterile method for assessing clinical viability during hypothermic storage of human cadaver kidneys and the subsequent recovery of renal function postrenal transplantation.     

Combined cold storage-perfusion preservation with a new synthetic perfusate

Based upon encouraging experimental results, we began employing a synthetic perfusate for cadaver kidney preservation. The new perfusate contains hydroxyethyl starch (HES) as the sole colloid for oncotic support; 107 cadaver kidneys were preserved and transplanted (93 primary, 14 nonprimary) using the HES solution and were compared with our previous experience of 180 cadaver kidneys (161 primary, 19 nonprimary) preserved and transplanted utilizing an albumin-based perfusate. All cadaver kidneys were locally harvested and preserved by machine perfusion. Donor and preservation characteristics in the HES (n = 61) and the albumin (n = 101) groups were comparable, with a mean preservation time of 30.9 hr. Cold storage in combination with hypothermic pulsatile perfusion (HPP) preservation was performed more often in the HES group (68.2% vs. 31.1%, P less than 0.001). Recipient characteristics were also comparable, and all received quadruple immunosuppressive therapy with sequential/Minnesota antilymphoblast globulin/(MALG)/cyclosporine. After primary transplantation, the incidence of immediate function (82.6% vs. 89.2%), preservation-related dialysis (14.9% vs. 8.6%), and primary nonfunction (2.5% vs. 0) were similar between the 2 groups, with trends favoring the latter HES data. One-month serum creatinine (1.8 vs. 1.7 mg/dl) and graft survival (95% vs. 97.8%) also were comparable. Similar trends were present in the retransplant group, including a significantly lower 1-month serum creatinine in the HES group (2.2 vs. 1.5 mg/dl; P less than 0.05). The preservation-related dialysis rate did not differ between primary and nonprimary transplants. Primary nonfunction has not occurred with our new perfusate. Combined cold-storage-HPP preservation with HES perfusate offers advantages over standard retrieval technology and provides excellent immediate allograft function.     

Successful human kidney preservation by intracellular electrolyte flush followed by cold storage for more than 48 hours

Transplantation of cadaver kidneys after flushing with an ice-cold intracellular electrolyte solution is inhibited by arbitrary time limits on cold ischemia. During the 25-month interval ending March 22, 1982 we transplanted 7 kidneys preserved by this method and cold-stored for 48.2 to 61.4 hours. Of the recipients 86 per cent required dialysis within 1 week after transplantation, the mean serum creatinine nadir within 1 month was 2.1 mg./dl. and the graft survival at 1 month was 71 per cent. The 1-year actuarial cadaver graft survival was 69.2 plus or minus 18.1 per cent. Kidneys preserved by this simple method can be transplanted successfully after 48 hours of simple cold storage.     

The effect of age and prolonged cold ischemia times on the national allocation of cadaveric renal allografts

BACKGROUND: National sharing of cadaveric renal allografts for perfectly matched kidneys (0 antigen mismatch) has improved outcome in the recipients of these kidneys despite increasing cold storage times. However, there may be limits to outcome improvement of matched kidneys based on age and cold storage time. MATERIALS AND METHODS: To determine if national sharing of kidneys based on matching improves outcome regardless of donor age and cold storage time, we evaluated the United Network for Organ Sharing (UNOS) Scientific Registry for all recipients of cadaveric kidney transplants between January 1, 1990 and July 31, 1998. We divided the recipients into four groups based on donor age and cold storage time. Group 1 comprised young donors (donor age <55 years) with average (<24 h) cold storage time; group 2, young donors with long (>/=24 h) cold storage time; group 3, older donors (donor age >/=55 years) with average cold storage time; and group 4, older donors with long cold storage time. RESULTS: A total of 64,046 recipients were evaluated: 35,061 (55%) in group 1, 21,264 (33%) in group 2, 4308 (7%) in group 3, and 3414 (5%) in group 4. Early graft performance progressively decreased from group 1 to group 4. Delayed graft function (DGF: dialysis requirement in the first 7 days posttransplant) was 18, 29, 33, and 42% (P < 0.0001); serum creatinine at 3 years (in mg/dl) was 1.70 +/- 0.8, 1.73 +/- 0.9, 2. 31 +/- 1.0, and 2.42 +/- 1.1 (P < 0.0001); 1-year graft survival was 87, 84, 79, and 77% (P < 0.0001); and 3-year graft survival was 77, 74, 63, and 62% (P < 0.0001, for groups 1 and 2 vs groups 3 and 4, respectively). The trends in DGF persisted through the groups in 0 antigen mismatched kidneys. CONCLUSIONS: Early function is adversely affected by prolonged cold storage, despite matching, in recipients of younger and older donor kidneys. Long-term function does not appear to be affected by prolonged cold storage. Recipients of kidneys from donors >/=55 years of age have significantly worse short- and long-term outcome and may not benefit from national sharing.     

The role of cold ischemia in a provincial organ-sharing program in the cyclosporine era

Prolonged cold ischemia has been associated with impaired early cadaver renal allograft function. The role of CsA in potentiating these effects is not well understood, but CsA has been implicated in promoting delayed graft function and potentiating renal ischemic injury. In order to establish whether CsA is safely tolerated by kidneys subjected to protracted cold ischemia, we examined patient and graft outcome in a series of 1081 patients receiving cadaver-kidney transplants over an 8-year period (1981-1988). All patients received a standard immunosuppressive regimen that included CsA. Overall actuarial 1-year patient and graft survival rates were 96% and 80%, respectively. Renal preservation was achieved either by pulsatile perfusion (n = 261, 24%) or simple cold storage (n = 820, 76%). Results were analyzed according to total cold ischemic time as follows: 0-23 hr (n = 512; range, 0-23.9 hr); 24-35 hr (n = 380; range, 24.0-35.9 hr); 36-47 hr (n = 161; range, 36.0-47.7 hr); greater than or equal to 48 hr (n = 28; range, 48.0-70.6 hr). These groups did not differ significantly in recipient age, sex, incidence of diabetes, number of pretransplant blood transfusions, level of presensitization, or HLA match. There were no differences in overall actuarial 1-year patient or graft survival rates, incidence of rejection, or renal function at 1 year. There was a higher incidence of impaired early graft function for kidneys preserved greater than or equal to 48 hr, but eventual graft outcome, including serum creatinine at 1 year, was unchanged. Delayed introduction of CsA resulted in improved 1-year graft survival (84.4% vs. 74.7%, P less than 0.05) compared to CsA treatment begun at the time of transplantation ("initial CsA"). This improvement was present regardless of total cold ischemia time. The incidence of permanent graft nonfunction, which has been previously reported to increase with CsA therapy, was influenced by the timing of CsA therapy (initial: 12%; delayed: 3%, P less than 0.05) but was not affected by duration of cold ischemia. Thus, safe preservation of cadaver kidneys for up to 70 h can be achieved by standard techniques even when CsA is incorporated into the immunosuppressive regimen. The most important determinants of graft survival in these patients are the timing of CsA therapy and the presence of early graft function, not the duration of renal preservation.     

Optimal pH for simple cold storage or machine perfusion of dog kidneys with UW solution

Metabolic suppression by temperature is a key to successful organ preservation. Additional methods for inducing metabolic suppression may further improve organ preservation. Extracellular acidosis has been shown to suppress warm anoxic injury to various isolated cells. Acidosis may suppress enzymes with a pH optimum at the pH of the cytosol (pH 7.3). In this study, the combination of hypothermia and acidosis was used to determine if it would improve renal preservation. Dog kidneys were cold-stored (CS) for 48 h in University of Wisconsin (UW) solution with the pH adjusted to 6.4, 6.8, 7.4, or 7.8. Kidneys were also machine-perfused (MP) for 3 days with the gluconate perfusion solution (Belzer's machine perfusion solution, MPS) at pHs similar to those tested for CS. Renal function (serum creatinine, SCr) and survival were recorded in immediate contralateral nephrectomized recipients. On the basis of maximum SCr values, kidneys preserved by CS or MP were best preserved at pHs of 7.4 or 7.8. At a pH of 6.8, SCr values were elevated and returned to normal at a slower rate than in those preserved at higher pHs. This study shows that acidosis is not cytoprotective to cold-stored dog kidneys and causes preservation/reperfusion injury. Received: 25 August 1997 Received after revision: 18 November 1997 Accepted: 14 January 1998     

An In Vivo Autotransplant Model of Renal Preservation: Cold Storage Versus Machine Perfusion in the Prevention of Ischemia/Reperfusion Injury

There is increasing proof that organ preservation by machine perfusion is able to limit ischemia/reperfusion injury in kidney transplantation. This study was designed to compare the efficiency in hypothermic organ preservation by machine perfusion or cold storage in an animal model of kidney autotransplantation.
Twelve pigs underwent left nephrectomy after warm ischemic time; the organs were preserved in machine perfusion ( n  = 6) or cold storage ( n  = 6) and then autotransplanted with immediate contralateral nephrectomy. The following parameters were compared between the two groups of animals: hematological and urine indexes of renal function, blood/gas analysis values, histological features, tissue adenosine-5'-triphosphate (ATP) content, perforin gene expression in kidney biopsies, and organ weight changes were compared before and after preservation.
The amount of cellular ATP was significantly higher in organs preserved by machine perfusion; moreover, the study of apoptosis induction revealed an enhanced perforin expression in the kidneys, which underwent simple hypothermic preservation compared to the machine-preserved ones. Organ weight was significantly decreased after cold storage, but it remained quite stable for machine-perfused kidneys.
The present model seems to suggest that organ preservation by hypothermic machine perfusion is able to better control cellular impairment in comparison with cold storage.     

Twenty-four hour canine renal preservation by pulsatile perfusion, hypothermic storage, and combinations of the two methods.

A comparison of the effectiveness of two renal preservation techniques was studied in 30 cannine renal pairs. In the absence of warm ischemia, 24-hr preservation by pulsatile perfusion was not significantly superior to hypothermic storage. When 15 min of warm ischemia was added as an additional insult, pulsatile perfusion afforded significantly better early function than cold storage. Combinations of pulsatile perfusion and hypothermic storage following 15 min of warm ischemia were superior to hypothermic storage alone, but inferior to pulsatile perfusion. Kidneys initially perfused for 6 hr and then cold-stored functioned slightly better than kidneys perfused for 18 hr after initial cold storage.     

Effect of Euro-Collins' or UW solution on the early graft function following cadaveric kidney transplantation

From November 1985 to March 1990, 55 cadaveric kidney transplants were performed under cyclosporine therapy. All kidneys were harvested from non-heart beating donors and cold stored after being flushed with EC solution (Group I, n = 27) or UW solution (Group II, n = 28). Warm ischemic time (min) in groups I and II were 7.1 +/- 3.3 and 6.9 +/- 2.3, respectively. Cold ischemic times (hr) in groups I and II were 6.9 +/- 2.4 and 8.4 +/- 2.8, respectively. Mean numbers of days for postoperative dialysis were 14.0 +/- 7.9 in group I and 7.9 +/- 5.8 in group II (p less than 0.05). One-month creatinine (mg/dl) was 2.9 +/- 2.8 in group I and 1.75 +/- 1.0 in group II (NS). One-month graft survivals (%) in groups I and II were 81.4% and 92.8%, respectively. In conclusion, UW solution has provided beneficial effect of preservation on ischemic damaged kidney and appears to be method of choice in non-heart beating cadaveric kidney transplantation.     

The relative effects of warm and cold ischemic injury in an experimental model of nonheartbeating donor kidneys

BACKGROUND: Ischemia reperfusion injury (I/R) leads to delayed graft function and remains an important problem in renal transplantation. The aim of this experimental study was to assess the effects of warm (WI) and cold ischemia (CI) in models of heartbeating (HBD) and controlled/uncontrolled nonheartbeating donor (NHBD) kidneys. METHODS: A reperfusion model utilizing cardiopulmonary bypass technology was used to perfuse isolated porcine kidneys with autologous blood after the following conditions: 0 min WI+2 h cold storage (CS); 0 min WI+18 h CS; 10 min WI+2 h CS; 10 min WI+18 h CS; 25 min WI+2 h CS; 25 min WI+18 h CS. Renal function was measured over a period of 3 hr. RESULTS: Renal functional parameters were not significantly different between 0, 10, 25 WI with 2 h CS [AUC creatinine (Cr) decrease of 1057+/-177, 1102+/-260, and 1245+/-143 micromol/L h, P=0.338; AUC creatinine clearance (CrCl) of 37.7+/-15.8, 36.2+/-21.7, 19.8+/-9.1 ml/min/100 g h, P=0.099]. After 18 h CS, renal function was severely impaired in the 10 and 25 WI groups compared to 0 min WI [AUC Cr of 2156+/-401, 2287+/-148, 1563+/-395 micromol/L h, P=0.037; AUC CrCl of 2.2+/-1.7, 1.5+/-1.5, 21.7+/-13.4 ml/min/100 g h, P=0.007). CONCLUSION: Warm ischemia of up to 25 min was only detrimental to renal function when kidneys were subsequently preserved in cold storage for 18 hr. This data suggests that limiting the cold storage period is of paramount importance when transplanting kidneys subjected from nonheartbeating donors.     

Verapamil improves rat hepatic preservation with UW solution

Verapamil, a calcium channel blocker, improves myocardial preservation during cold cardioplegia and protects against renal damage during periods of warm and cold ischemia. To determine if verapamil could prevent ischemic damage to livers during and after cold storage, harvested rat livers were flushed with either University of Wisconsin (UW) solution or UW solution with 25 mg/liter verapamil. Twenty rats were used in each group. After 24 hr of storage at 4 degrees C, livers were perfused with oxygenated blood through the portal veins for 2 hr at 37 degrees C and pH 7.4. Liver enzymes, electrolytes, and perfusate flow rate were determined at 30-min intervals. At 90 min of perfusion, the verapamil group of livers had less elevation of AST (110 +/- 17 IU/liter vs 172 +/- 25 IU/liter, P less than 0.05), ALT (115 +/- 21 IU/liter vs 210 +/- 34 IU/liter, P less than 0.05), and LDH (962 +/- 170 IU/liter vs 1452 +/- 253 IU/liter, NS). Verapamil livers produced more bile than controls (6.9 +/- 1.9 microliters/g vs 2.3 +/- 1.7 microliter/g, P less than 0.05) and maintained a higher portal flow rate throughout the perfusion. Both groups showed similar reduction in liver weights after storage (3.9 +/- 0.9% vs 2.8 +/- 0.7%) and required the same amount of bicarbonate for correction of acidosis during perfusion (2.6 +/- 0.2 mM vs 2.8 +/- 0.2 mM). Light microscopic exam after perfusion showed hepatocyte damage in 30% of control livers, but 0% of verapamil livers. We conclude that verapamil-treated rat livers showed less damage and better function upon reperfusion after 24 hr of cold storage. This agent may be clinically useful as an additive to the UW preservation solution for livers.