The beneficial effect of superoxide dismutase on the rat liver graft

We performed orthotopic liver transplantation in male Wistar rats and investigated the effect of superoxide dismutase (SOD) on the liver graft. Animals were divided into the four following experimental groups. Group I was an untreated control group, group II received oxygen, group III received SOD and group IV received both oxygen and SOD. The dose of SOD was 3 mg/kg which was injected intravenously into both donors and recipients during the operation. Oxygen was given through an oxygen inhaler to both donors and recipients during the operation. The preservation time of the liver graft ranged from 4 hours and 41 minutes to 5 hours and 40 minutes. The survival after liver transplantation was compared among groups I, II, III and IV. Group IV showed a significantly higher survival rate than groups I and II by two weeks after liver grafting, but there was no statistical difference in the survival rates between groups III and IV. These results indicate the beneficial effect of SOD on the rat liver graft and may implicate oxygen free radicals in the pathogenesis of ischemia/reperfusion injury in liver grafts.     

Hyperacute rejection in porcine liver transplantation. I. Clinical characteristics, histopathology, and disappearance of donor-specific lymphocytotoxic antibody from serum

Hyperacute rejection following orthotopic liver transplantation remains an extremely unusual occurrence. In this study, we examined a porcine model of liver transplantation in which recipient animals were sensitized prior to transplantation with three serial full-thickness skin grafts. Three experimental groups were studied. Group I recipients (n = 6) were specifically sensitized against their liver donors with biweekly skin grafts followed by hepatic grafting. Group II recipients (n = 6) underwent third-party skin graft sensitization prior to liver transplantation. Group III recipients (n = 6) underwent liver grafting without sensitization. Mixed lymphocyte cultures were done before each skin graft and prior to transplantation. Lymphocytotoxic antibody (LCTA) titers were measured before the first skin graft, at weekly intervals thereafter, intraoperatively, and daily postoperatively until death. Intraoperative and postmortem liver biopsies were obtained in all recipients. Five of six recipients in Group I died within 4 hr of hepatic revascularization. The remaining animal survived for four days. Mean survival time in group I was 0 +/- 0.7 days. In contrast, MST in groups II and III were 4.0 +/- 1.2 and 6.2 +/- 1.3 days, respectively. The MST in group I was significantly shorter than in groups II and III (P less than 0.026 and P less than 0.005, respectively). There was no significant difference in survival between groups II and III. MLC reactivity between recipients and skin donors increased progressively following each skin graft, reaching a peak just prior to liver transplantation. LCTA titers also increased following each skin graft, reaching peak levels immediately prior to hepatic grafting. Intraoperative LCTA titers decreased within 2 min of graft revascularization and were undetectable within 4 hr. In group III (unsensitized recipients), MLC reactivity was low and at no time was LCTA detectable. Histologic examination of the livers from group I recipients showed parenchymal hemorrhage, endophlebitis, and neutrophil infiltration. Histologic examination of postmortem liver biopsies from animals in groups II and III revealed acute cellular rejection. In conclusion, hyperacute rejection resulting in graft failure and recipient death can be consistently produced in a porcine model of hepatic transplantation by donor-specific sensitization of the recipient. It is postulated that high titers of donor-specific antibody are required to exceed the liver's capacity for antibody absorption and elimination and produce the clinical picture of hyperacute rejection.     

Limited effectiveness of FK506 administration for ongoing rejection in heterotopic rat heart transplantation

A comparison was made of the histological findings for myocardial tissue of heterotopic transplanted rat hearts administered with FK506. ACI rats were used as donors and Lewis rats as recipients. FK506 was used for 6 days except for group I (control group). Group II received 0.32 mg/kg/day of FK506 from the day of operation while group III was given the same dosage from the 4th day after transplantation. Group IV was given 1.28 mg/kg/day of the agent from the day of grafting and group V received the same dose from the 4th postoperative day. The graft survival time was longer for all groups given FK506, but was significantly longer only for groups administered with FK506 from the day of operation. Histological studies performed 10 and 20 days after transplantation showed that a moderate rejection was seen in about half of the grafts receiving FK506 from the 4th day after grafting. An ultra-structural study of these cases showed that infiltrating large lymphocytes still remained in the interstitial tissues and that the cytoplasmic organelles of the myocytes had been focally destroyed. These results suggest that, although FK506 suppressed any further rejection, the effect might be limited and the myocardial changes of the cardiac graft might persist even after administration for ongoing rejection.This work was supported by a Ministry of Education Grant (A) 03770873.     

Combined treatment with endothelin- and PAF-antagonists reduces posttransplant lung ischemia/reperfusion injury.

BACKGROUND: Pathophysiologic changes of posttransplant lung ischemia/reperfusion injury are mediated by redundant cellular and humoral mechanisms. We investigated the protective effect of combined administration of platelet activating factor (PAF) and endothelin (ET) antagonists after prolonged ischemia in a small animal lung transplantation model. METHODS: Orthotopic left lung transplantation was performed after 20 hours cold ischemia in male Fischer (F344) rats weighing 200-250 g. Group I served as control. In Group II, donors received 1 mg/kg body weight of the endothelin antagonist TAK-044, and recipients 2 mg/kg. Group III was treated with the PAF antagonist TCV-309 (donor: 50 microg/kg; recipient: 100 microg/kg) (Takeda Chemicals Ltd.). Group IV received a combined treatment with both substances at the same dosage. Twenty-four hours after reperfusion, the native contralateral lung was occluded to assess gas exchange of the graft only, and 5 minutes later the thoracic aorta was punctured for arterial blood gas analysis (n = 5). In other animals (n = 5), lung tissue was frozen 24 hours after reperfusion and assessed for myeloperoxidase activity (MPO) and thiobarbituric acid reactive substances. RESULTS: Combined inhibition of PAF and ET-1 at the receptor level resulted in significantly improved graft function as compared to controls (Group I), and to groups treated with either TAK-044 or TCV-309. This was determined by a higher arterial oxygen content (112 +/- 9 mmHg, p = .00061 vs control, 48 +/- 5 mmHg), reduced MPO activity (0.35 +/- 0.02 deltaOD/mg/min, p = .000002 vs control, 1.1 +/- 0.1 deltaOD/mg/min) and reduced lipid peroxidation (59.5 +/- 2.5 pmol/g, p = .011 vs control, 78.5 +/- 4.1 pmol/g). The improvement of arterial oxygen (Group II 77 +/- 10 mmHg, p = .027 vs control; Group III 84 +/- 8 mmHg, p = .0081 vs control) and reduction of MPO activity (Group II 0.85 +/- 0.061 deltaOD/mg/min, p = .017; Group III 0.92 +/- 0.079 deltaOD/mg/min, p = .058) in groups treated with either a PAF antagonist or an ET antagonist was significantly less than in Group IV. CONCLUSIONS: Combined donor and recipient treatment with an ET antagonist and a PAF antagonist results in superior posttransplant graft function 24 hours after reperfusion, suggesting a synergistic role of ET-1 and PAF in the mediation of reperfusion injury in this model. Single treatment with either of the antagonists revealed only a slight improvement compared to untreated controls.     

Implication of advanced donor age on the outcome of liver transplantation

Historically, age has been considered to be a relative contraindication for organ donors. The use of elderly donors for liver transplantation remains controversial due to the fear of inferior outcome. According to United Network for Organ Sharing (UNOS) data, the proportion of older donors has been increasing annually. This study describes the short‐ and long‐term outcomes for transplantation of elderly donor livers. Three hundred and seventy‐four primary liver transplantations, which had been performed at the University of Virginia Health System from 7 February 1988 to 31 December 1998, were included. Graft survival, incidence of primary non‐function, and hepatic artery thrombosis (HAT) after transplantation according to the different age groups of liver donors were analyzed. Cases were analyzed by donor age (group I, n=106: aged <20 yr; group II, n=217: aged between 20 and 49 yr; group III, n=51: aged ≥50 yr), and by donor age in comparison with recipient age (group IV, n=65: recipients transplanted with organs from donors within 5 yr of their age; group V, n=266: recipients from donors> 5 yr younger than their age; group VI, n=43: recipients from donors> 5 yr older than their age). Group III or VI (group of advanced donor age) and group II or V (control group) were compared by age, gender, race, body weight, height, pre‐transplantation cytomegalovirus (CMV) status of the recipients donors, cause of brain death of donors, total or warm ischemic time, ABO matching, and degree of human leucocyte antigen (HLA) mismatching. No significant difference in 5 yr graft survival was found between the groups by donor age (p=0.604) and by donor age compared with recipient age (p=0.567). Moreover, no significant differences in the incidence of primary non‐function and HAT after transplantation were found between the groups by donor age and by donor age compared with recipient age. Older donors were more likely to be women and to have antibodies to CMV, as well as to have died by cerebrovascular causes. Race, body weight, height of both recipients and donors, total or warm ischemic time of grafts, ABO matching, and degree of HLA mismatching were not significantly different between the groups. We conclude from this study that advanced donor age is not a contraindication to liver transplantation if careful assessment of donors is made on a case‐by‐case basis. There is a need to maintain an open mind with regard to the use of livers from older donors due to the current situation of serious organ shortages.     

Efficacy of PGI2 analog in preventing ischemia reperfusion damage of liver grafts from living donors

In living-related transplantation, warm ischemia/reperfusion damage (IRD) of liver grafts is inevitable during harvesting. In this study, we investigated the effects of prostacyclin (PGI₂) on IRD of liver grafts in the rat liver transplant model. Donor rats underwent 30-min warm ischemia of part of the liver (right lateral and medial lobes). After 10 min of reflow, the ischemic partial livers were flushed with Ringer's lactate and immediately transplanted into untreated recipients. Donor animals were divided into two groups: group I received vehicle, and group II received PGI₂ analog OP-41483 (OP, 500 ng/kg per min, i. v.) during the donor operation. One-week survival was studied and cellular adenine nucleotide levels of donor livers were assayed by high-performance liquid chromatography (HPLC). Donor treatment with PGI₂ analog group II significantly improved 1-week survival (86%), in comparison with the controls group I (25%). The levels of total adenine nucleotides (TAN, μmol/g dry wt) of the grafts just before implailtation were well maintained by PGI2 treatment (12.22), as compared with the controls (10.36). In summary, PGI2 treatment of the donor maintained high energy metabolism of the liver graft after IRD and improved the survival of recipients after transplantation. Our study suggested that PGI₂ treatment of donors improves viability in liver grafts from living donors thus and increases graft availability for transplantation.     

Alternative applications of cyclosporin A to improve kidney allograft survival

This study applies cyclosporin A as a donor pretreatment prior to organ harvesting or as a graft pretreatment during preservation of canine kidney allografts by hypothermic pulsatile perfusion or hypothermic storage. All recipients except those in Group IX received minimal immunosuppression with azathioprine after transplantation (5 to 2.5 mg. per kg. per day). No significant differences in survival (X +/- SD) were observed between the 3 control groups which were either 1) flushed with untreated Ringer's lactate solution and immediately transplanted (Group I, no. = 8, 14 +/- 3.33 days), 2) preserved by hypothermic pulsatile perfusion for 24 hours (Group II, no. = 7, 12.0 +/- 8.92 days), or 3) hypothermically stored for 24 hours (Group III, no. = 7 13.1 +/- 11.6 days). A trend towards improved survival was seen in the 2 groups of animals that received kidneys that had been graft pretreated with cyclosporin A (12.5 mg.) during 24 hours preservation by either hypothermic pulsatile perfusion (Group IV, no. = 10, 17.4 +/- 13.32 days, p less than .25) or hypothermic storage (Group V, no. = 6, 8 +/- 12.75 days, p less than .25). Survival of recipients in Groups VI (no. = 6) and VII (no. = 9) who received kidneys whose donors had been pretreated with 25 and 50 mg. per kg. respectively was dependent on the dosage of cyclosporin A used. Donor pretreatment at 50 mg. per kg. was deleterious to kidney function (Group VI, 2.16 +/- 1.47 days, p less than 0.0005). Donor pretreatment with 25 mg. per kg. did not significantly improve survival over control groups (15.66 +/- 12.9 days). Recipients in Groups VIII (no. = 10) and IX (no. = 6) were transplanted with kidneys from cyclosporin A pretreated donors (15 mg. per kg.). These kidneys also received cyclosporin A graft pretreatment (10 mg.) during 24 hours of hypothermic storage. The only difference between Groups VIII and IX was that the animals in Group IX received minimal amounts of cyclosporin A (5 mg. per kg. per day) after transplantation. Combined donor and graft pretreatment yielded improved kidney allograft survival (Group VIII, 21.7 +/- 13.36 days, p greater than .10, Group IX, 20.83 +/- 14.2 days, p greater than .10). However, there was no significant difference observed as a result of the different immunosuppressive protocols used in Groups VIII and IX. These results indicate a trend towards improved renal allograft survival under certain conditions, after donor and graft pretreatment with cyclosporin A.     

Attenuation of decompressive hypoperfusion and cerebral edema by superoxide dismutase

This study tested the hypothesis that ischemia-reperfusion injury initiated by the superoxide anion radical is a major component of postdecompression hypoperfusion and cerebral edema, and could be attenuated by superoxide dismutase (SOD). A supratentorial extradural balloon was placed in 20 fasting, lightly anesthetized, mechanically ventilated dogs and inflated in 0.5-ml increments (0.07 ml/sec) at 15-minute intervals. The end-point of balloon expansion was the onset of an isoelectric electroencephalogram, near-arrest of hemispheric cerebral blood flow (CBF) (measured by H2 clearance), and the appearance of a suprainfratentorial intracranial pressure gradient, which was held for 15 minutes. The in vivo development of brain edema was detected by measuring brain elastic response (BER) extradurally, and was correlated with postmortem measurement of brain water content (gravimetry); blood-brain barrier integrity was tested by Evans blue dye given after the insult. After decompression, the dogs were randomly assigned to one of four treatment groups: Group I received hyperventilation (PaCO2 28 +/- 1 mm Hg, mean +/- standard deviation); Group II received furosemide (2.4 mg/kg) and pentobarbital (10 mg/kg) every 8 hours; Group III received 20% mannitol in a 1.4-gm/kg bolus plus furosemide, 0.5 mg/kg; and Group IV received SOD, 15,000 U/kg every 15 minutes for 3 hours. At 4 hours of decompression Group IV had significantly greater recovery in local CBF and BER than Groups I, II, and III (p less than 0.05). The 24-hour survival rate was 20% for Group I, 60% for Group II, 80% for Group III, and 100% for Group IV. The survival rate appeared to correlate with a variable degree of postmortem intraparenchymal hemorrhages, blood-brain barrier disruption, and moderate to severe brain edema for Groups I, II, and III. In contrast, Group IV had the least brain edema (p less than 0.05) and Evans blue dye extravasation (p less than 0.05) and the fewest intraparenchymal hemorrhages. These data support the hypothesis that, under the experimental conditions described here, the superoxide anion plays a major role in the pathophysiology of postdecompression ischemic edema.     

The immunoprotective effect of Sertoli cells coencapsulated with islet xenografts is not dependent upon Fas ligand expression

Coencapsulation with Sertoli-enriched testicular cell fractions prolongs islet graft survival time compared with islet encapsulation alone in a highly discordant tilapia (fish)-to-mouse xenotransplantation model. Here we investigate whether Fas ligand (Fas-L) expression by testicular Sertoli cells is responsible for this additional protective effect. Sertoli-enriched testicular cell fractions (7 x 10(6) cells) harvested from either Fas-L-defective (group I) or Fas-L-positive (group II) mice were coencapsulated in alginate gel spheres with fish islets and then transplanted into streptozotocin-diabetic Balb/c recipients. Group III mice received encapsulated islets without coencapsulated Sertoli cells. After transplantation, blood glucose levels were monitored three times per week. Mean graft survival times for the three groups were: group I = 35.6 +/- 10.2 days (n = 9), group II = 31.3 +/- 9.4 days (n = 7), and group III = 23.3 +/- 2.2 days (n = 6) (ANOVA, p = 0.043). Coencapsulation, regardless of the Fas-L status of the Sertoli cell donors, modestly prolonged graft survival. There was no significant difference between Fas-L-deficient and Fas-L-positive donors. Our results suggest that Fas/Fas-L interaction is not responsible for the additional protection afforded to encapsulated discordant islet xenografts by coencapsulation with Sertoli cells.     

Transplantation of pediatric kidneys to adult recipients: an analysis of 13 cases

INTRODUCTION: The shortage of cadaveric donors for kidney transplantation has prompted many centers to expand the criteria used for donor selection to increase the organ supply. The use of cadaveric pediatric kidneys has been suggested as a means to overcome the shortage. However, some studies indicate that kidneys from pediatric donors show inferior results to those from adult donors. In this retrospective study we examined the outcome of kidney transplantation using cadaveric pediatric donors. MATERIALS AND METHODS: From October 1990 to May 2002, 13 adult patients received pediatric renal transplants including two that were transplanted en bloc. The patients were divided into two groups based upon donor age: group I donors were 18 months to 6 years old; the seven recipients were of mean age 47.3 years. Group II donors were 7 to 15 years old; the six recipients were of mean age 43.6 years old. Cyclosporine-based immunosuppressive regimens were used in both groups. RESULTS: The patient survival rate was 85.7% in group I and 100% in group II. The graft survival rates at the first and third posttransplant year in group I were 71.4% (5/7) and 57.1% (4/7) and in group II, 66.7% and 50%, respectively. The frequency of urinary complications in group I was 28.5% (2/7) and in group II 33.3% (2/6). There was one case of venous thrombosis in group II. CONCLUSION: Pediatric renal grafts may be used with reasonable safety. However, surgical complications remain a significant problem especially with younger pediatric grafts.     

Transplantation of liver grafts from older donors: impact on recipients with hepatitis C virus infection

INTRODUCTION: Older donor allografts are being accepted for liver transplantation (LTx) due to shortage of organs. Hepatitis C virus (HCV) infection-related disease is presently the most common indication of LT in the United States. We studied the impact of donor age on patient and graft survivals in patients with HCV infection. PATIENTS AND METHODS: One hundred fifty four consecutive HCV(+) LTx recipients (117 men, 37 women) were studied. The mean follow-up period was 41.0 +/- 30.2 months. The population was divided into four groups according to donor age: group I (< or =20 years); group II (21 to 40 years); group III (41 to 60 years); group IV (>60 years). RESULTS: Thirty-two (20.8%) patients died during follow-up and 16 patients (10.4%) required retransplantation. The actuarial 7-year patient survivals for groups I, II, III, and IV were 87.1%, 73.7%, 69.3%, and 68.5%, respectively (P = .4). Patient survivals for donor age groups III + IV (n = 95) and groups I + II (n = 59) were 68.9% and 77.2%, respectively (P = .19). The 7-year graft survivals for groups I, II, III, and IV were 82.7%, 71.8%, 65.8%, and 62.5%, respectively (P = .17). Graft survivals for groups III + IV and groups I + II were 58.4% and 76.2%, respectively (P = .03). CONCLUSION: Patient and graft survivals for HCV-positive liver transplant recipients in this study decreased progressively as the donor age increased. Patient and graft survivals were best for group I recipients. There were significant differences in graft survivals when recipients were grouped with a cutoff donor age of 40 years.     

Experimental studies on the effects of superoxide dismutase on warm ischemic-reperfusion injury of the lung]

Transient impairment of the transplanted lung in early postoperative period is one of difficult problems in lung transplantation. It is likely that reperfusion injury of the warm ischemic lung is contributory. The purpose of this study is to evaluate the effects of superoxide dismutase (SOD) on reperfusion injury of warm ischemic lung. Thirty mongrel dogs were divided into four groups. In group I (n = 6), the left lung with complete hilar stripping was placed in warm ischemic state under deflation for 1 hour. In group II (n = 9), the left lung with complete hilar stripping was kept in warm ischemic condition under inflation. Group III (n = 6) animals with same manipulation as group I received superoxide dismutase (SOD 20 mg/kg) before reperfusion. Group IV (n = 9) animals underwent same manipulation as group II and received SOD (20 mg/kg) before reperfusion. Before warm ischemia, immediately after reperfusion, and 1 and 2 hours, blood gases, left pulmonary vascular resistance were measured under the occlusion of right pulmonary artery. Extra vascular lung water content (EVLW) was measured at autopsy and lung was processed for histology. In group II, III and IV, blood gases and EVLW showed significantly better values than group I. In group I and III, left pulmonary vascular resistance increased prominently after reperfusion, however did not change in group II and IV. From these results, we concluded that inflated lung reduced the extent of pulmonary edema after reperfusion and SOD was effective in preventing warm ischemic damage even in deflated lung.     

Benefits of quadruple immunosuppressive therapy in recipients of living related donor kidneys. A review of 855 operations.

Eight hundred fifty-five living related donor transplant recipients were analyzed according to 15 potential risk factors with regard to patient and graft survival according to immunosuppression. Group I, 1968 to 1983, (n = 440 patients) received azathioprine and prednisone; group II, 1984 to 1987, (n = 229 patients) received triple therapy--azathioprine, prednisone, and cyclosporine; and group III, 1988-1991, (n = 186 patients), quadruple therapy--azathioprine, prednisone, cyclosporine, and Minnesota antilymphocyte globulin. Three important risk factors included immunosuppression, tissue typing, and race. Groups II and III had improved allograft survival over group I (p = 0.03). Patients with two haplotype matches had similar survival in all three groups. Kidney survival in one-haplotype-matched recipients improved in group II and was equal to that of the two-haplotype-matched patients in group III. Cyclosporine improved allograft survival in both races when combined with azathioprine and prednisone. Quadruple therapy improved early survival in one-haplotype black patients, even though long-term results remained better in whites. Cyclosporine did not improve graft survival in two-haplotype recipients. The addition of cyclosporine and quadruple therapy did not increase morbidity and mortality rates.     

Lazaroid U74389G ameliorates ischemia-reperfusion injury in the rat lung transplant model.

We investigated the effect of Lazaroid U74389G on ischemia-reperfusion injury in the rat orthotopic left lung transplantation model. Five groups of reperfused lungs were studied. In group I, donor lungs were transplanted after 12 hours of preservation in University of Wisconsin (UW) solution at 4C. In groups II, III, and IV, Lazaroid was intravenously administrated at a dose of 1 mg/kg, 8 mg/kg, and 15 mg/kg, respectively, to the donors 30 minutes before preservation and also to the recipients 30 minutes before reperfusion after 12 hours of storage in UW solution at 4C. In group V, Lazaroid was added to the UW solution (80 micromol/l), and also was administered intravenously (6 mg/kg) 30 minutes before reperfusion. After 1 hour of reperfusion, gas exchange function and tissue lipid peroxide levels were significantly improved in Lazaroid-treated groups III, and V compared with no treatment group I. Histologic damage was less severe in groups III, IV, and V than in group I. These findings suggest that Lazaroid U74389G ameliorates ischemia-reperfusion injury in the rat lung transplants by inhibiting lipid peroxidation, regardless of whether it is administrated intravenously or given as an additive to the preservation solution.     

Influence of pancreas and kidney transplant function on recipient survival

The aim of this study was to evaluate long-term survival after simultaneous pancreas and kidney (SPK) transplantation in relation to function of both grafts. Among 67 recipients who received SPK transplants between 1988 and 2004, 35 had follow-up longer than 18 months, and were divided into: group I (n = 20), recipients with good function of both grafts; group II (n = 7), patients who had lost transplanted pancreas but had still good kidney graft function; group III (n = 8), patients who had lost both grafts. Comparison of survival rates and analysis of the reason of mortality among groups was performed. The cumulative survival rate was significantly higher in group I than in group III (after 3, 5, 10 years: 100%, 100%, 80% vs 75%, 50%, 37%, respectively). Cumulative survival rate for group II after 3, 5, 10 years was 100%, 100%, 33%, respectively. There were no significant differences in survival rates between groups I and II and between groups II and III. In group I deaths for cardiovascular event and for leukemia were noted. In group II deaths due to cardiovascular event and sepsis were observed. In group III all patients died due to cardiovascular events and the mean time from loss of pancreas and kidney graft function to death was: 75 +/- 51 months (range from 19 to 142), and 49 +/- 26 months (range 19 to 99), respectively. Good pancreas and kidney graft functions prevent death due to cardiovascular event.     

Double versus single renal allografts from aged donors

BACKGROUND: The age limit of the cadaver kidney donors is increasing in response to the growing demand for renal transplantation. Simultaneous double kidney transplantation (SDKT) with kidneys obtained from elderly adults has been proposed to increase the transplantation number and improve its results. However, if SDKT is performed when there are no clear indications, a negative effect could be produced on the total number of transplanted patients as both kidneys would be used for only one recipient. MATERIAL AND METHODS: In December 1996 we designed a transplantation protocol to be able to extend the selection of cadaver kidney donors with normal serum creatinine levels without establishing any age limit. A pregraft renal biopsy was always performed to analyze the glomerulosclerosis (GE) percentage whenever the donors were 60 years of age or older. A SDKT was performed in a single recipient when the donor age was 75 years or older or when the donors between 60 and 74 years old had a GE rate of more than 15%. On the contrary, a single kidney transplantation was performed in two different recipients for kidneys from donors between 60 and 74 years of age with a GE rate of less than 15%. Kidneys having GE rates of more than 50% were discarded for transplantation. Donor kidneys from subjects younger than 60 years of age were always used for a single kidney transplantation. RESULTS: Based on the above mentioned protocol, from December 1996 to May 1998, 181 patients received a kidney transplantation in our hospital. These patients were divided into three groups: group I which included the SDKT recipients (n=21), group II or single kidney recipients from 60- to 74-year-old donors (n=40), and group III or recipients from <60-year-old donors (n=120). The mean follow-up time was 15+/-5 months (range 6-24). Mean donor age was 75+/-7 years in group I, this was significantly higher than in group II (67+/-4, P<0.001) and group III (37+/-15, P<0.001). The primary nonfunction rate was low in the three groups, there being no statistically significant differences (5, 5, and 4%, respectively). A significantly greater percentage of patients from group I (76%) presented immediate renal graft function as compared with group II (43%, P<0.01) and III (50%, P<0.05). The acute rejections rate was very low in all three groups (9.5, 7.5, and 22%, respectively) with significant differences between groups II and III (P<0.05). No significant differences between the different groups were observed for one year actuarial patient survival (100, 95, and 98%, respectively) or graft survival rates (95, 90, and 93%, respectively). The 6-month serum creatinine levels were excellent in the three groups, although there were significant differences between groups I and II (1.6+/-0.3 vs. 1.9+/-0.6 mg/dl, P<0.05), II and III (1.9+/-0.6 vs. 1.4+/-0.4 mg/dl, P<0.001), and I and III (P<0.05). CONCLUSIONS: Simultaneous double kidney transplantations make it possible to use kidneys from extremely elderly donors (>75 years) or those whose GE>15%. In addition, kidneys from donor 60-74 years old in which the GE<15% can be used for single kidney transplantations in two different recipients with excellent results.     

肝移植多模式策略的初步探讨

目的：总结多种临床肝移植技术的经验。方法：对2000年9月至2002年3月完成的25例临床肝移植（27次移植手术）的资料进行回顾性分析。包括尸肝移植14例,活体肝移植11例,再次尸肝移植1次,减体积再次肝移植1次。结果：11例活体肝移植的供体中,10例为患者之母亲,1例急诊成人右叶活体肝移植供体为患者之妹。供肝方式：扩大左半肝6例,右半肝3例,右半肝2例;切取供肝重量270－620g。全组存活24例,1例成人活体肝移植受体于术后72d死于不可逆转的严重排斥反应。肝炎患者采用拉米呋啶加抗HVB－Ig治疗,10例乙肝、肝硬化患者术后随访时间4－21个月,复查HVB－DNA均为阴性。所有肝豆状核变性受体术后随访复查6－17个月,铜氧化酶、肝功能均正常。本组主要并发症包括：腹腔出血2例,需再次剖腹探查止血;ARDS 5例;急性肾功能衰竭2例;排斥反应4例,其中1例导致死亡。结论：综合开展包括尸体肝移植、活体肝移植、减体积肝移植等在内的各项技术,充分利用有限的供肝,是优化肝移植资源,提高移植疗效的重要途径。     

Pulmonary macrophages are involved in reperfusion injury after lung transplantation

BACKGROUND: Reperfusion injury is a perplexing cause of early graft failure after lung transplantation. Although recipient neutrophils are thought to have a role in the development of reperfusion injury, some researchers have shown that neutrophils are not involved in its earliest phase. Intrinsic donor pulmonary macrophages may be responsible for this early phase of injury. Using the macrophage inhibitor gadolinium chloride, we attempted to investigate the role of pulmonary macrophages in reperfusion injury after lung transplantation. METHODS: Using our isolated, ventilated, blood-perfused rabbit lung model, all groups underwent lung harvest followed by 18-hour storage (4 degrees C) and blood reperfusion for 30 minutes. Group I served as a control. Group II received gadolinium chloride at 7 mg/kg 24 hours before harvest. Group III received gadolinium chloride at 14 mg/kg 24 hours before harvest. RESULTS: Group III had significantly improved arterial oxygenation and pulmonary artery pressures compared with groups I and II after 30 minutes of reperfusion. CONCLUSIONS: The earliest phase of reperfusion injury after lung transplantation involves donor pulmonary macrophages.     

Recipient treatment with trimetazidine improves graft function and protects energy status after lung transplantation.

BACKGROUND: Ischemia-reperfusion injury remains an important obstacle to successful lung transplantation. Trimetazidine is an anti-ischemic drug that restores the ability of ischemic cells to produce energy and reduces the generation of oxygen-derived free radicals. The aim of this study was to assess the protective effect of trimetazidine after prolonged ischemia in lung transplantation. METHODS: Rat single-lung transplantation was performed in 4 experimental groups (n = 5 each). In all groups, transplantation was performed after 18 hours of cold (4 degrees C) ischemia. All donor lungs were flushed with low-potassium dextran-glucose (LPDG) solution that also contained 500 microg/liter prostaglandin estradiol (E(1)). Groups studied included: Group I: flush solution was administered containing 10(-6) mol/liter trimetazidine (TMZ), neither donor nor recipient treatment given; Group II: donors were treated with 5 mg/kg intravenous TMZ 10 minutes prior to harvest, but the flush solution did not contain TMZ; Group III: recipients treated with 5 mg/kg intravenous TMZ 10 minutes before reperfusion, and flush solution contained 10(-6) mol/liter trimetazidine; Group IV: ischemic control group. After 2 hours of reperfusion, oxygenation was measured and lung tissue was frozen and assessed for adenosine triphosphate (ATP) content, myeloperoxidase (MPO) activity and thiobarbituric acid-reactive substances (TBARS). Peak airway pressure (PawP) was recorded throughout the reperfusion period. RESULTS: Group III showed significantly higher levels of ATP content (11.1 +/- 5.01 pmol vs Group I, 3.36 +/- 1.8 pmol, p = 0.008; vs Group II, 4.7 +/- 1.9 pmol, p = 0.03; vs Group IV, 0.7 +/- 0.2 pmol, p = 0.008), better oxygenation (442.5 +/- 26.5 mm Hg, vs Group I, 161.06 +/- 54.5 mm Hg; vs Group II, 266.02 +/- 76.9 mm Hg; vs Group IV, 89.4 +/- 14.7 mm Hg, p = 0.008) and reduced lipid peroxidation (TBARS) (0.15 +/- 0.03 nmol/g; vs Group I, 1.04 +/- 0.76 nmol/g; vs Group II, 0.69 +/- 0.4 nmol/g; vs Group IV, 2.29 +/- 0.4 nmol/g, p = 0.008). PawP and MPO activity were comparable in the 4 study groups. CONCLUSION: Recipient treatment with TMZ provided significant protection of energy status, better oxygenation and reduced lipid peroxidation. Our data suggest that TMZ may be an important adjunct in the prevention of post-transplant lung ischemia-reperfusion injury.     

不同冷保存时间的热缺血供肝在肝移植中的疗效

目的 探讨不同冷保存时间的热缺血供肝在肝移植中的疗效.方法 回顾性分析2006年1月至2007年12月中山大学附属第一医院收治的154例肝移植受者采用热缺血时间≤10 min的无心跳供者肝脏进行肝移植的疗效.根据冷保存时间将患者分为3组:<8 h为Ⅰ组,58例;8～12 h为Ⅱ组,62例;>12 h为Ⅲ组,34例.采用方差分析、t检验和X~2检验分析3组肝移植术后ALT峰值、并发症、移植肝存活和受者生存情况的差异.结果 3组受者术后均未发生原发性移植肝无功能.随访时间8～32个月,Ⅰ组受者的ALT峰值、感染发生率、胆道并发症发生率、移植肝存活率和生存率分别为(482±357)U/L、12%(7/58)、12%(7/58)、86%(50/58)和88%(51/58),Ⅲ组受者分别为(1274±608)U/L、29%(10/34)、26%(9/34)、68%(23/34)和71%(24/34),两组比较差异有统计学意义(t=5.X~2=4.28,6.77,4.51,4.28,P<0.05);而Ⅱ组受者仅ALT峰值达到(953±424)U/L,与Ⅰ组比较差异有统计学意义(t=4.76,P<0.05).结论 热缺血时间≤10 min的供肝能够耐受12 h的冷保存损伤,超过此时限,移植术后胆道并发症和感染的发生率显著升高,移植肝存活率和受者生存率显著降低.