Native and graft intestinal blood flow and its intramural distribution in iso- and allografted rats.
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Biomedical subjects
Publications and source records attributed to S M Greenstein.
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The small intestine (SI) is highly sensitive to oxygen free radical-induced injury. The most common preservation solution, University of Wisconsin (UW) solution, does not adequately prevent free radical-induced injury. Lazaroids, and U74389G in particular, are a new class of compound that are potent inhibitors of superoxide-mediated lipid peroxidation. We studied the added influence of U74389G to 18-hr cold preservation of rat SI in UW solution. Three groups of rats were studied. In group 1, SI was excised and reperfused immediately. In group 2, SI was stored in UW solution at 4 degrees C for 18 hr. In group 3, U74389G was given to the SI graft before storage and again before reperfusion. Blood reperfusion of the grafts was achieved via connection to the superior mesenteric artery and portal vein of support rats. Functional recovery was assessed using a maltose tolerance test. Weight changes were calculated and histologic studies done. After 30 and 60 min of reperfusion, maltose uptake in group 3 was significantly better than that of the group 2, and returned to control levels. Significantly more tissue swelling was noted in group 3 over control, but the magnitude was less than that of group 2. Less transmural necrosis and villous blunting were noted in group 3 versus group 2; the appearance of the mucosa in group 3 approached that of group 1. We conclude that the use of U74389G treatment in addition to cold storage in UW solution improves recovery of graft function and minimizes morphologic damage to the small intestinal mucosa.
In the Banff classification, arteritis and tubulitis are regarded as the principal histological lesions indicating acute renal allograft rejection. To test this claim, we examined 51 biopsies obtained from 21 children and young adults with transplant rejection. Two reviewers, blind to the clinical course, graded the biopsies according to the Banff scheme. In patients without significant tubulitis (borderline changes), rejection tended to be reversed easily (88%), often with methylprednisolone pulse (52%). In patients with arteritis or significant tubulitis (Banff I-III), rejection was reversed in only 23% (P < 0.001), in 9% with steroids, and in 14% with OKT3. Salvage of the graft was achieved in 26 of 35 (74%) with a score < 5 but in only 1 of 12 (8%) with a score > or = 5 (P < 0.001). All 6 patients with vasculitis lost their grafts despite methylprednisolone pulse and OKT3. We conclude that the Banff classification predicts accurately the outcome of renal allograft rejection in children and may aid in choosing appropriate therapy.
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Cyclosporine (CsA)-induced alterations in organ blood flow (BF) and function have been studied in kidney and pancreatic transplants. In this study, we assessed the effect of prolonged CsA administration on graft tissue BF and absorption from transplanted rat small intestine (SI). Isogeneic SI transplantation was performed in Lewis rats. Animals were grouped based upon the following treatment schedules: no treatment for 1 week in group 1; 0.15 ml/kg/day im olive oil for 1 week in group 2; 0.15 ml/kg/day olive oil for 1 week and then 0.1 ml/kg/day for 5 weeks in group 3; 15 mg/kg/day im CsA for 1 week in group 4; and 15 mg/kg/day CsA for 1 week and then 10 mg/kg/day for 5 weeks in group 5. Group 6 was the same as group 5 but CsA was withdrawn for 1 week prior to assessment. Maltose absorption was measured to evaluate graft absorptive function. BF and its intramural distribution to mucosal and serosal/muscularis layers were determined using the radioactive microsphere technique. Perfusion pressure was measured to calculate vascular resistance (VR). One week of CsA of administration in group 4 resulted in a significant increase in mucosal VR (68.4 +/- 15.5 versus 46.9 +/- 8.7 U/g, P < 0.01) and significant decreases in mucosal BF (1.21 +/- 0.25 versus 1.80 +/- 0.38 ml/g/min, P < 0.01) and maltose absorption 30 min after loading (168.9 +/- 21.1 versus 214.4 +/- 28.4 glucose mg/dl, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Between January 1, 1984 and December 31, 1991, 471 cadaver renal transplants were performed. We reviewed 130 transplants, which were biopsied 30 minutes to 1 hour after the establishment of renal allograft blood flow. Analysis showed a significant difference in 2-year graft survival rate between the groups with and without arteriosclerosis (71.8% versus 65.9%, p < 0.05). Arteriosclerotic changes were noted more frequently in biopsies from older donors (37 versus 28 years, p < 0.005). There was also a difference in ischemic time between the groups with and without tubular degeneration (30.1 hours versus 26.7 hours, p < 0.02), which did not correlate with the need for dialysis in the perioperative period (48% versus 49%, p > 0.8).
Fractional excretion of sodium (FENa) has been used in the diagnosis of acute renal allograft failure on the assumption that poor allograft perfusion should result in a low FENa. However, many patients receive medications which affect the active transport of Na+ and thus FENa. In contrast, the fractional excretion of urea (FEurea) is mostly dependent on passive forces and is therefore less influenced by drug therapy. To test the hypothesis that FEurea might be more useful than FENa in evaluating graft failure, we compared FEurea with FENa during 79 episodes of acute renal allograft dysfunction due to acute rejection (AR), cyclosporine nephrotoxicity (CsA-Nx), viral infection, or bacterial infection in 32 children and young adults with renal transplants. There was no significant difference between groups in FENa. However, FEurea was significantly lower (P < 0.05) in patients with CsA-Nx (32.6 +/- 1.9%) and viral infection (32.9 +/- 3.2%) than those with AR (45.1 +/- 1.7%) or bacterial infection (38.9 +/- 2.5%). FEurea was < 35% in 20 of 28 (71.4%) episodes of CsA-Nx and 8 of 11 (72.2%) of viral infection, but only 5 of 36 (13.9%) of AR (P < 0.05). FEurea was also measured during stable graft function, 7-14 days prior to allograft dysfunction. CsA-Nx was associated with a 30.5 +/- 8.3% decrease in FEurea. FEurea did not change in patients with AR. Based on these findings, we present an algorithm to aid in the differential diagnosis of acute renal allograft failure.
Preservation of renal allografts following spontaneous rupture is a surgical challenge. Salvage was attempted in 3 patients. Despite successful repair in all 3, transplant nephrectomy was ultimately required in 2 patients because of irreversible rejection. The third patient is doing well forty-eight weeks after transplantation.
Results of pediatric renal transplantation have been variable. We evaluated our experience with renal transplantation in children less than 5 years old to determine its safety and efficacy. Of the 428 renal transplants done at our institution from August 1983 to December 1989, 14 were performed in 13 children 13 to 50 months old (mean age 34 months). All of the patients were small for age with height standard deviation scores ranging from -1.7 to -4.5. Patient survival, allograft survival and statural growth were used as determinants of successful outcome. Followup was complete in all patients, including renal function studies and serial height measurements. Growth velocity standard deviation scores were calculated. Patient survival was 100%. Allograft survival was 100% 2 to 7.3 years after transplantation for living related donor recipients whereas 1-year graft survival was poor (40%) for cadaveric graft recipients. Of 10 patients with good graft function at 1 year 9 demonstrated improvement in the height standard deviation score. Seven of 10 patients demonstrated significant catch-up growth (growth velocity standard deviation score greater than 0, p = 0.04). Our study supports the safety and efficacy of renal transplantation in young children. Early transplantation using living-related donor organs is the optimal therapy to prevent growth retardation and allow the young child with end stage renal disease to have a normal life.
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Injury from oxygen free radicals has been suggested to be of greater significance in the preservation of small intestine than of other organs. To determine if using the free radical scavenger, superoxide dismutase (SOD), with University of Wisconsin (UW) solution would improve preservation of small intestine, acute and chronic studies were conducted. Thirty-centimeter segments of small intestine from Lewis rats were flushed with and stored in Collins, UW, or SOD-modified (8000 U/ml) UW solution at 4 degrees C for 18 hr. For the acute study, small intestine segments were subsequently reperfused using support rats. The support rats in the UW/SOD group also received SOD (1750 U, iv) at the onset of reperfusion of small intestine. After 2 hr of reperfusion, maltose absorption and weight gain of small intestine were determined. For the chronic study, small intestine segments were transplanted as isografts. SOD (1750 U, iv) was also given to recipients prior to reperfusion of grafts in the UW/SOD group. Long-term effects were determined by recipient survival for at least 17 days. Results showed the small intestine in the UW/SOD group had the best recovery of mucosal absorption (256 +/- 39 versus 202 +/- 21 in the Collins group, P less than 0.01), the least percentage weight gain (19 +/- 3% versus 25 +/- 5% in the UW group and 38 +/- 5% in the Collins group, P less than 0.01), and the best 17-day survival rate (9/12 versus 2/9 in the UW group, P less than 0.025, and 0/8 in the Collins group, P less than 0.01) among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)
At four medical centers, 98 patients with stable asthma, histories of nighttime awakening at least three times weekly and nighttime declines of pulmonary function of at least 15%, who were not taking oral adrenergic agonists, were randomly treated with either oral repeat-action albuterol sulfate (Proventil Repetabs), 4 mg in the morning and 4-16 mg at bedtime, or a placebo for 2 weeks. All patients were required to have nocturnal symptoms of asthma, with prior use of bronchodilators other than oral adrenergic agonists to be eligible for the study. The patients maintained a diary of asthma symptom scores and recorded peak flow rates at home at bedtime and in the morning. They had spirometry (FEV1, FVC, and PEFR) after a 1-week baseline stabilization period, and after 1 and 2 weeks of double-blind oral therapy as noted above. Efficacy was evaluated by changes in the bedtime and morning peak flow rates, changes in the number of nighttime awakenings, results of office spirometry testing, and by physician and patient global evaluations of response to therapy. Of the 98 patients in the study, 47 received oral albuterol, and 51 received placebo. The patients on albuterol had a statistically significant reduction in the number of nighttime awakenings (p less than or equal to 0.01), as compared with the patients on placebo; this included both the average number of awakenings per week (p = 0.04), and the mean number of nights with awakenings per week (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
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Fertility and potential fertility were evaluated in 9 young men on cyclosporine A therapy following renal transplantation. Semen analysis was normal in most parameters in 8 patients as was testicular hormonal function. Of 4 men who had attempted to impregnate their wives 3 succeeded. Cyclosporine A does not seem to affect adversely fertility in men.
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