摘要:

The results of a series of 32 rat liver transplants are described to analyze the efficacy of components of UW solution. Rat livers were stored at 4°C in standard UW solution or one of three simplified variants for 24 hr prior to orthopic liver transplantation. In standard UW solution (solution A) the one-week survival rate was 3 of 8. Using solution B, which differs from solution A in the omission of hydroxyethyl starch and adenosine, the one-week survival rate was 2 of 8. Solution C, a further-simplified version of solution B with omission of allopurinol, Bactrim, and insulin, gave a one-week survival rate of 3 of 8. Solution D is identical to solution B except that the sodium and potassium concentrations are reversed. Using this solution, 5 of 8 rats survived more than one week.We conclude that the effectiveness of UW solution is maintained in a substantially simplified form, and that solution D, with the Na/K ratio reversed to give a high Na variant, may improve survival.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

A new technique for 24-hr cardiac preservation is described utilizing very low flow perfusion (microper-fusion) with a cold flush solution. Rabbit hearts were arrested with UW solution and then perfused with the same solution through the aortic root at 0°C at a rate of 3–6 ml/gm heart weight/24hr. When tested on an ex vivo working heart model, the cardiac ouput (CO) was 28.72±7.69 ml/g/min compared with fresh UW flushed controls of 26.48±2.25 ml/g/min. Both oxygenated high-flow perfusion with a more conventional perfusate and 24-hr ice storage with UW led to inferior results. Omission of the colloid, hydroxyethyl starch (HES), from the UW solution or prolonged shelf storage were also significantly detrimental. When a previously untested colloid, polyethylene glycol 20,000, was substituted for HES for microperfusion, excellent cardiac function was obtained. In fact, the mean CO of this group, 31.91±5.70, was significantly above that of fresh HES-UW unstored controls. The suggestion that the UW solution might be improved by this substitution warrants further study.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

This experimental study in dogs was designed to investigate whether maximal loading produces atrial natriuretic factor (ANF) release and whether this physiological peptide is involved in the improvement of the early renal function recovery after acute ischemia. The experimental protocol included a renal artery occlusion for 45 min in uninephrectomized dogs and the measurement of various parameters of renal function over 2-hr period after declamping.There were 3 experimental groups. In the control group (I) (n=10), the dogs received, after ischemia, an isotonic saline solution infusion at a rate of 0.2 ml/kg/min. In group II, (n=10) the animals underwent acute volemic expansion (1 ml/kg/min) with whole blood (hematocrit ≈25%) during the ischemic period, and after declamping, an isotonic saline infusion (NaCl 0.9%) infusion at the same rate as in the control group. In group III, (n=8) the dogs only received NaCl 0.9% (0.2 ml/kg/ min) before ischemia and α human ANF (3.6 ng/kg/min) dissolved in saline after ischemia and during the 2 hr of the renal recovery period.Volemic expansion induced a highly significant increase of the cardiac filling pressures concomittant with a prompt but transient 5–6-fold increase in ANF levels (357±92 pg/ml versus 60±4.1 pg/ml in controls at the time of declamping [P<0.05]). With these higher plasma ANF levels in overloaded animals, we observed, 2 hr after declamping, considerably improved renal function recovery in terms of glomerular filtration rate—37.5%±8.7 versus 11.8±3.9%; urinary sodium excretion rate—53.89 μeq/min versus 5.36±1.2 μeq/min …

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

These experiments compared the effect of a five-day course (days −1 to +3) of cyclosporine therapy coupled with pretransplant (day −1) administration of donor-specific antigen (whole blood or splenocytes) on either pancreatic or heart allograft survival in the Buffalo to Lewis rat donor-recipient combination. CsA therapy alone significantly (P<0.001) prolonged both heart (16.2±1.6 days) and pancreas (12.5±1.5 days) graft survival when compared with nonimmunosuppressed control heart and pancreas grafts (7.7±1.8 and 7.9±1.0 days, respectively). Pretransplant transfusion with either 2 ml of BUF whole blood or 2 × 108red cell-free splenocytes on day −1 also resulted in a significant (P<0.001) prolongation of heart survival (14.0±1.2 and 14.0±1.6 days, respectively) but did not improve pancreas allograft survival (9.4±1.5 and 8.5±1.0 days, respectively). Combination CsA and antigen therapy further improved heart graft survival to 26.5±6.1 days (whole blood) and 28.8±5.8 days (splenocytes) but did not improve pancreas graft survival over that of CsA therapy alone. Extension of CsA therapy by adding two additional 3-day cycles on days 10–12 and 17–19 further improved heart graft survival both after CsA alone (35.2±3.2 days) and after CsA coupled with whole-blood transfusion (45.3±8.6 days), but did not have a salutary effect on pancreas allograft survival. Portal vein administration of donor antigen was equally effective as systemic inoculation in prolonging heart graft survival when the splenocytes were given alone (11.6±1.7 days) or in combination with CsA (27.6±3.6 days). Conversely, pancreas allograft survival was not beneficially effected by portal antigen administration whether or not CsA was given. These data demonstrate the ability of pretransplant donor-specific antigen administration and short-term CsA therapy to significantly prolong rat heart allograft survival across a strong MHC histocompatibility barrier—but, surprisingly, they also demonstrate the failure of this regimen to have a salutary effect on pancreas allograft survival.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Rat liver transplantation was utilized to study the effect of hepatic iron on the control of iron absorption. Six iron-loaded and six normal livers were transplanted into normal or iron-loaded animals. Iron absorption was measured pretransplant and 10 days posttransplant by total-body counting (59Fe). The animals were loaded with oral carbonyl iron to produce a predominantly parenchymal hepatic iron distribution and with parenteral iron dextran to produce a predominantly reticuloendothelial iron distribution. The carbonyl iron-loaded livers contained 175±6.6, the iron dextran livers 180± 41, and the normal livers 6.6±2.8 μmol FE/g dry wt. Iron absorption was unchanged by the insertion of normal livers into normal animals. The transplantation of carbonyl iron-loaded livers into normal animals caused a marked decrease in iron absorption posttransplant from 7.2±0.9% to 0.3±0.4% (P<.001) posttransplant. Neither the transplantation of iron dextran-loaded livers into normal animals nor the transplantation of normal livers into iron-loaded animals significantly altered iron absorption at 10 days posttransplant. These results are consistent with the hypothesis that hepatocyte iron stores are a major determining factor controlling iron absorption.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The concept of islet exhaustion maintains that exposure of pancreatic islets to hyperglycemia and other stresses leads to islet dysfunction and irreparable damage. The process of pancreatic transplantation places many stresses on islets (e.g., counter-regulatory hormones, steroids, cyclosporine toxicity). As practiced by some centers, it may be important to administer exogenous insulin in the postoperative period to provide islet rest. Using a porcine pancreas transplant model that simulates clinical transplantation, we studied 2 groups: 1 group (n=8) received constant insulin infusion for 7 days after transplantation; the control group (n=5) received vehicle only. The islets in the insulin infusion group were rested as evidenced by a significantly decreased mean C-peptide level (0.27±0.04 ng/ml) as compared to the control group (0.66±0.08 ng/ml) (P<0.05). After insulin infusion was discontinued, intravenous glucose tolerance testing found insulin, C-peptide and glucagon responses were not different between groups. Glucose clearance was also comparable; K values were −1.79 and −1.60 in the insulin infusion and control groups, respectively. In conclusion, islet rest by insulin infusion for 7 postoperative days did not improve subsequent pancreas transplant endocrine function.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The anatomical possibility of resecting the left lobe of the liver (segments II and III) in living subjects and using it for transplantation was evaluated. A group of 60 cadaveric livers were dissected at autopsy. The vascular and biliary elements of the left lobe were isolated and the lobe was resected and evaluated for possible grafting.The left lobe was 12–28% (mean 19.4%) of the liver mass. An extrahepatic segment of the left hepatic vein was isolated in 95% of specimens. Arterial blood supply to the left lobe consisted of a single artery (92%) or two arteries (8%).A single portal vein segment to the left lobe (type I) was: found in 35% livers. Portal vein branches originated from a common orifice (type II, 35%) or separately (type III, 30%) from the left portal vein, and in these instances, preparation of a portal segment necessitated partial section of the left portal vein wall.Biliary drainage was extrahepatic in 56 livers and consisted of a single duct (type I, 78%), or two ducts (type II, 15%).The resected left lobe was evaluated as satisfactory (single hepatic vein and artery, types I or II portal vein, type I bile duct) in 48% of cases, while a less-satisfactory lobe (type III portal vein or type II bile duct) was obtained in 33%.It was found anatomically difficult or impossible to resect the left lobe for possible transplantation in 11 (19%) liver specimens.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

OKT3 antibody therapy is effective in the treatment of renal allograft rejection. However its exact mode of action is unknown. Following OKT3 administration, peripheral blood lymphocytes fail to express the CD3 antigen, although other membrane antigens are relatively preserved. In this way the lymphocytes are unable to respondtoforeign antigens. It is not known whether this modulation of CD3 on lymphocytes occurs within the rejecting allograft. Ten patients who received OKT3 therapy for steroid-resistant renal allograft rejection were studied. The aim of the study was to examine whether OKT3 antibody therapy altered the degree or the relative composition of the inflammatory infiltrate and to assess whether 0KT3 treatment resulted in modulation of CD3 on intragraft lymphocytes. The study involved immunoperoxidase examination of biopsy material and flow cytometric analysis of peripheral blood lymphocytes obtained before and during treatment with OKT3 antibody. The results show that the total number of infiltrating leukocytes decreased after 5 days of treatment (3215±700 cells/1. 0 mm2of tissue before vs. 1730±635 at day 5; P < 0.001). The relative proportions of macrophages, total lymphocytes, CD4 +ve and CD8 +ve cells did not alter during therapy. Despite marked modulation of peripheral blood lymphocytes (CD3/CD2 ratio 0.89±0.13 before vs. 0.10± 0.11 during treatment,P< 0.001), there was no evidence of modulation of intragraft lymphocytes (CD3/CD2 ratio 0.98± 0.14 before vs. 0.90±0.21 during treatment, P=NS). Although OKT3 antibody therapy is effective clinically at improving renal allograft rejection, this study demonstrates that it does not appear to cause modulation of the CD3 antigen on intragraft lymphocytes.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Hyperlipidemia and hypertension, two major risk factors for accelerated atherosclerosis, undoubtedly contribute to the excessive cardiovascular morbidity and mortality experienced by renal transplant recipients. The present survey of posttransplant hyperlipidemia in 500 cyclosporine-treated patients documented a 37.6% incidence of hypercholesterolemia, which occurred within 6 months posttransplant in 82% of patients. An etiologic relation to corticosteroid therapy was suggested by the strong correlation between prednisone doses and cholesterol levels, by the reduced cholesterol levels in patients undergoing steroid withdrawal, and by the reduction in hypercholesterolemia to 13% by 3 years posttransplant when steroid doses were less than 10 mg daily. Hypertriglyceridemia, which was present in 14.7% of the patients, was more severe under CsA-prednisone compared with azathioprine-prednisone therapy. Hypertriglyceridemia, which occurred later in the posttransplant course than hypercholesterolemia, strongly correlated with an excessive percent relative weight and elevated serum creatinine but not with steroid or CsA doses. Increasing age, diabetes mellitus, β-blockers and nephrotic syndrome contribute to posttransplant hyperlipidemia in the CsA-Pred era as they did in the azathioprine era of immunosuppression.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

In this study, we have compared the influence of CsA and pred/aza on the immunocompetence in man. Therefore, kidney-transplant recipients were tested for their primary keyhole limpet hemocyanin and secondary (tetanus and KLH) humoral immune responses and their primary dinitrochlorobenzene and secondary (recall antigens) cellular immune responses. We demonstrate that primary immune responses are inhibited by CsA, whereas secondary immune responses are relatively resistant. Pred/aza therapy seems to inhibit all cellular immune responses, as we demonstrated before, as well as the primary humoral immune responses. Secondary humoral immune responses are only slightly affected by pred/aza. Our results provide a strong argument for starting immunosuppression with CsA, either with or without a low-dose pred.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID