摘要:

The single-flush technique of lung preservation is thought to be enhanced by prostaglandin treatment. In order to test this hypothesis, ten beagle dogs underwent thoracotomy and in situ flush perfusion of the excluded left lung with 30 ml/kg of cold, modified Euro-Collins' solution. Group 1 (n=5) received pretreatment with 30 ng/kg/min of PGI2by infusion and as an additive to the flush (20 μg/L). Group 2 (n=5) received no PGI2and served as controls. Following 60 min of warm ischemia, the left lung was reperfused, the contralateral lung excluded, and the animal ventilated at a fixed FiO2of 0.4 for 4 hr. The severity of reperfusion injury was assessed by arterial oxygenation and hemodynamic measurements and, following sacrifice, by lung weight gain and bronchoalveolar lavage and ultrastructural studies.PGI2therapy resulted in significant amelioration of reperfusion injury, with superior oxygenation at both 1 and 4 hr (PaO2at 1 and 4 hr, respectively; PGI2: 145 mmHg ± 17.0 and 114 ± 11.2; no PGI2: 59 mmHg ± 5.8 and 51 ± 4.5;P<0.01 at both times), lower pulmonary vascular resistance index at 4 hr (PVRI; PGI2: 913 dynes sec cm-5m-2± 91; no PGI2: 1239 ± 68;P<0.05) and lower lung weight (PGI2: 76 g ± 4; no PGI2: 146 ± 10;P<0.001). Bronchoalveolar lavage studies revealed an influx of neutrophils following reperfusion that was less marked in the PGI2group (increase in % neutrophils; PGI2: 50.4 ± 6.7; no PGI2: 76.9 ± 6.0;P<0.05). Lung injury score assessed by electron microscopy was lower in the PGI2group (PGI2: 5.2 ± 1.1; no PGI2; 8.1 ± 0.5;P<0.05). It is concluded that PGI2treatment is protective against ischemic lung injury in this model.

ISSN:0041-1337    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Urinary levels of immunoreactive insulin (IRI) were measured in 18 pigs subjected to pancreatic allograft transplantation with exocrine drainage into the urinary tract. Fifteen pigs were given no immunosuppressive therapy while 3 pigs received cyclosporine and prednisolone. The onset of rejection was defined as an increase in the serum levels of anionic trypsin (irAT). Urinary levels of IRI were compared between normo-and hyperglycemic pigs representing slow and fast rejectors. It was possible to measure insulin in the urine from all these pigs with a pancreatic allograft, and the urinary IRI levels increased after an intravenous injection of secretin and cholecystokinin. We found that urinary IRI response to secretin and cholecystokinin declined during rejection. By contrast, baseline, unstimulated urinary IRI levels did not correlate with rejection. No advantage was seen in the determination of urinary IRI when compared to determination of urinary irAT. In pigs not treated with immunosuppressants (with irreversible rejection), stimulated urinary levels of IRI and irAT were highly useful as graft-function indicators, whereas in immunosuppressed pigs (with reversible rejection episodes) they seemed to complement each other.

ISSN:0041-1337    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Calcium channel blockers have recently been shown to improve pulmonary and myocardial preservation. The effect of verapamil on hypothermic lung preservation was investigated using an isolated ventilated rabbit lung perfusion model. In phase 1, preserved lungs were not flushed prior to extraction. Four groups of five animals were studied: group 1 (no verapamil), group 2 (verapamil administration prior to extraction), group 3 (verapamil at reperfusion only), group 4 (verapamil both prior to extraction and at reperfusion). In phase 2, two groups of five animals received pulmonary artery flush with low potassium (4 mmol/L), 2% low-potassium dextran (LPD) solution; group 1 (without verapamil), group 2 (flush and reperfusion with verapamil). As in phase 1, lungs were stored for 30 hr at 10°C prior to reperfusion. In phase 3, the protocol was identical to phase 2, except that the storage time was extended to 48 hr.PO2(mean ± SE) of effluent blood in lungs treated with verapamil prior to extraction (122.8 ± 5.0 mmHg) was significantly increased in comparison with lungs not receiving verapamil (69.0 ± 3.3 mmHg) or only receiving verapamil at the time of reperfusion (87.1 ± 11.9 mmHg). Gas exchange after 30 hr storage was equivalent in lungs flushed with LPD with or without verapamil. However verapamil did provide an advantage when preservation times were extended to 48 hr (62.3 ± 8.5 mmHg, 46.9 ± 2.3 mmHg).

ISSN:0041-1337    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Cyclosporine metabolites (CM) were compared with cyclosporine for their in vitro and in vivo immunosuppressive, nephrotoxic, and hepatotoxic effects using (A) in vitro mixed lymphocyte induction of monocyte/macrophage procoagulant activity (PCA), an accurate marker of allograft rejection; (B) in vitro toxic effects on renal cells in culture; and (C) a unidirectional rejection model of rat small intestinal transplantation (SIT). CM were composed of OL1, OL17, OL18, and two additional peaks C and H, (peak C: mass = 1235, 15.3% of total CM, peak H: mass = 1205, 6.3% of total CM). In vitro, CM fully suppressed the one-way mixed lymphocyte culture-induced PCA from 52.5 ± 8.2 mU/106PBM to the basal level 22.3 ± 6.6 mU/106PBM (P<0.01), which was comparable to CsA (21.3 ± 5.5 mU/106PBM). Lewis rats that had received Lewis-Brown Norway F1hybrid intestinal allografts when treated with CM, demonstrated near-normal histology with minimal signs of rejection as compared with the fulminant clinical and histological rejection observed in the control (untreated and Cremaphor/NaCl treated) animals. PCA was markedly elevated in the control animals, 278±172 (untreated) and 160 ± 98 mU/106PBM (Cremaphor/normal saline treated), whereas CsA-treated allogeneic transplants expressed only basal levels of PCA (14.0 ± 4 mU/106PBM) (P<0.01), associated with normal histology. CM-treated animals expressed PCA levels of 27.0 ± 10 mU/106PBM, which was significantly different from both control and CsA treated animals (P<0.01). In contrast to CsA-treated animals, CM-treated allogeneic transplants demonstrated no apparent renal or hepatic toxicity, as measured by blood urea nitrogen (25.3 ± 9.5 vs. 10.0 ± 5.3 mg/dl), alkaline phosphatase (160.7 ± 29.3 vs. 100.3 ± 19.5 U/L), and aspartate transaminase (96.7 ± 23.7 vs. 61.7 ± 11.7 U/L) (P<0.01). Similarly, in contrast to CsA, CM had minimal or no toxicity in renal epithelial and mesangial cells in culture, as measured by minimal or no inhibition of DNA, RNA, and protein synthesis. These results suggest that CM have potent

ISSN:0041-1337    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The present studies show clearly that both dexamethasone and insulin can be omitted without altering the efficacy of UW. Adenosine and glutathione are both helpful additives, as is allopurinol. These findings suggest an important role of reperfusion injury after preservation, and confirm the benefits of adding pharmacological agents likely to reduce this injury. Cold ischemic damage was significantly ameliorated by UW solution in this stringent model of rat kidney preservation for 48 hr. A substantially simplified modification of UW solution has been shown to give equally effective kidney preservation, after removal of hydroxyethyl starch, dexamethasone, and insulin. Adenosine, glutathione, and allopurinol have been confirmed as helpful pharmacological additives. These findings have defined some of the mechanisms of effectiveness of UW solution and suggest avenues of further exploration to improve simple hypothermic storage and to prevent reperfusion injury.

ISSN:0041-1337    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The capacity of specifically targeted erythrocytes to inhibit free radical—mediated injury to the endothelial cell after cold preservation, and improve liver function was studied in two experimental models: An isolated perfused rat liver (IPRL) system and syngeneic orthotopic rat liver transplantation. In the IPRL model, livers were preserved in University of Wisconsin solution for 24 h at 4°C. At the end of the preservation period, livers were flushed with lactated Ringer's (control), immunoerythrocytes (IES), or blank intact erythrocytes prior to warm reperfusion for 2 h using an assanguinous Krebs-Henseleit buffer. Production of superoxide (02) anion during warm reperfusion in the IES-treated liver was reduced by 65% as compared with controls (P<0.001) and by 74% (P<0.001) when compared with blank erythrocyte-treated livers. Endothelial cell preservation, as assessed by levels of purine nucleoside phosphorylase (PNP), was much better in the IES-treated group (P<0.001) when compared with untreated livers. Hepatocellular preservation was markedly improved in the IES-treated livers.In the syngeneic liver transplantation model, livers were preserved in UW solution for 24 h at 4°C. Prior to implantation, livers were flushed with 5 ml of cold lactated Ringer's or immunoerythrocytes. Survival after three weeks was 60% in the IES-treated group and 30% in the untreated group. Survival in the IES-treated group was not significantly different from a control (no preservation) group.

ISSN:0041-1337    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

A total of 278 orthotopic rat liver grafts, without arterialization, were performed, in an attempt to determine which of the individual components of UW solution are essential. Livers were preserved by in situ flushing and cold storage with the following results: 56% of rats survived for 1 week after 9 hr of preservation with UW solution as compared with 44% using Marshall solution, and 10% using Collins solution. Having established LD 50 for UW solution, we then omitted its components one at a time and found that omission of HES, raffinose, allopurinol, adenosine, phosphate buffer, or MgSO4did not change survival after 9 hr of preservation. Omission of lactobionate, glutathione, and dexamethasone, respectively, resulted in decreased survival, whereas elimination of insulin surprisingly increased survival. In ensuing dose-response studies, the concentrations of lactobionate, glutathione, dexamethasone in UW solution proved to be optimal. Finally, livers were preserved with a solution containing only lactobionate, glutathione, dexamethasone, raffinose, and phosphate buffer, resulting in 53% animal survival, as compared with 56% for the unchanged UW solution. We conclude that UW solution can be simplified without loss of effectiveness in this model.

ISSN:0041-1337    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

In the present study the functional and morphologic effects of two pulmoplegic solutions are evaluated. Single left-lung allotransplantation with ligation of the right pulmonary artery was performed in 15 piglets (13–20 kg). The lungs were preserved after donor prostaglandin E-l treatment with single pulmonary artery flush with either modified Euro-Collins solution (mECS) (9 pigs) or oxygenated fluorocarbon emulsion (FC-43) (6 pigs) and transplanted after 6-hr storage in cold Physiosol solution. Tidal volumes of 15 ml/kg ± fr (18) with 40% inspired oxygen were used for ventilation during reperfusion. Function of the transplanted lung was monitored for 4 hr postoperatively by determining pa CO2and pa O2levels from arterial samples and by noninvasive monitoring of end-tidal CO2values and arterial oxygen saturations. Sequential morphologic changes in pulmonary artery flow surface and lung tissue were studied after 6-hr storage and 4-hr reperfusion, using light, scanning, and transmission electron microscopy (LM, SEM, TEM).There was no mortality. After transplantation the mECS group experienced significant hypoxia and hypercarbia and had low end-tidal CO2values as signs of defective oxygenation and gas exchange, whereas the FC-43 group was normoxic and normoventilated without disturbed elimination of carbon dioxide.After storage and reperfusion, LM showed signs of increased vascular permeability and reperfusion damage—more evident in the mECS group compared with the FC-43 group—while the lymphoid cell population was more intensely activated in the latter group.Electron microscopy after storage showed good overall preservation of structures in both groups. After reperfusion preservation of pulmonary artery flow surface and lung tissue was estimated to be moderate in the mECS group, whereas it was good-to-moderate in the FC-43 group by SEM (NS). TEM of lung tissue, however, showed significantly better-preserved alveolar epithelial lining in the FC-43 group compared with the mECS group. In conclusion, oxygenated fluorocarbon (FC-43) pulmoplegia gave better functional and morphologic preservation of lung grafts compared with modified Euro-Collins solution.

ISSN:0041-1337    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The study objective was first to investigate serum levels of tumor necrosis factor alpha, interleukin 1 beta, interferon gamma, interferon alpha, interleukin 2, beta-2-microglobulin (B2M), and urinary neopterin in patients after orthotopic liver transplantation; and second to relate their levels to clinical complications.The design used was the prospective observation study, and the setting used was the transplant unit of a university medical center. Serum samples were collected from 20 patients every alternate day from transplantation until discharge.The measurements and main results were as follows: concentrations of cytokines, B2M, and neopterin were performed using commercially available radioimmuno-assays. In seven out of nine patients with acute cellular rejections, elevated levels of TNF-alpha, IFN-gamma, IL-1, B2M, and neopterin were detected. The highest absolute levels of TNF-alpha were observed in patients with CMV disease. Increments in bacterial infections

ISSN:0041-1337    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Analysis of the genomic termini of Epstein-Barr virus can provide valuable insight into the cofactor role of EBV in the development of B cell lymphomas and lymphoproliferative disease. We report EBV genomic findings in pathologic specimens from 10 patients who developed lymphoma or lymphoproliferative disease after renal or bone marrow transplantation. Endonuclease restriction patterns of EBV genomic termini are highly variable in size in both the episomal and linear configuration. This variability in fragment size permits direct assessment of tissue clonality in EBV-infected material. Hybridization with terminus-specific probes also reveals configuration of viral genome (circular and latent vs. linear and replicative). Nine of 10 patients had tumors with mono-or biclonal episomal markers, and 4 of 10 had evidence of linear or replicative virus. Analyses of virally determined markers were compared to immunoglobulin gene rearrangement studies, histologic immunophenotyping, cytogenetics, and clinical outcome. These 10 cases represent a spectrum of lymphoproliferative disorders ranging from benign polyclonal to malignant monoclonal disease. The molecular data lend credence to two important aspects of viral pathogenesis: (1) the finding of a homogeneous episomal population in the monoclonal tumors suggests that EBV infection is an early event in tumorigenesis that occurs before clonal expansion; and (2) therapeutic efficacy of acyclovir has been shown only in presence of polyclonal disease but may impact on intermediate stages where linear replicative virus can be found. Finally, the various assessments of tumor clonality were compared, and although heterogeneity was seen among patients and among diagnostic methods, analyses at the molecular level using virus and immunoglobulin gene specific probes were concurrent and provide the more sensitive means for detection of clonality.

ISSN:0041-1337    

出版商:OVID    

年代:1990

数据来源: OVID