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S Fischer

Publications and source records attributed to S Fischer.

At least 109 records · Page 6Linked to original sources
PubMed2000

Ischemia reperfusion-induced dynamic changes of protein tyrosine phosphorylation during human lung transplantation.

BACKGROUND: We have recently demonstrated that more than 20% of lung cells undergo apoptosis within the first 2 hr of graft reperfusion after human lung transplantation. It has been found that changes of protein tyrosine phosphorylation are involved in the regulation of apoptosis in various cell types. METHODS: To determine the protein tyrosine phosphorylation status and related biochemistry changes, lung tissue biopsies were collected from six human lung transplant procedures after cold ischemic preservation (2-5 hr at 4 degrees C), after completing the implantation procedure (approximately 1 hr), and 1 or 2 hr after graft reperfusion. Western blotting was performed to determine protein tyrosine phosphorylation and several signal transduction proteins. Protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) activities were also measured. RESULTS: Protein tyrosine phosphorylation was significantly increased after lung implantation and before reperfusion, and significantly decreased during the first 2 hr of graft reperfusion. The activity of Src PTKs was reduced by 50% during graft reperfusion, which was associated with a decrease of Src proteins and human actin filament associated protein, a cofactor for Src activation. PTP activity significantly decreased after lung implantation and remained at a low level 1 hr after reperfusion. After 2 hr of reperfusion, however, PTP activity returned to the basal level. CONCLUSION: These dynamic changes of PTK and PTP likely explain the observed alterations of protein tyrosine phosphorylation. The significant decrease in protein tyrosine phosphorylation may be related to the observed apoptotic cell death during human lung transplantation.

Apoptosis↗
PubMed2000

Quality of life in ALS depends on factors other than strength and physical function.

OBJECTIVES: To study patients with ALS to determine the following: 1) the relationship between physical function and quality of life (QOL); 2) the instruments that best reflect patients' own ratings of QOL; and 3) whether spiritual/religious factors play a role in determining QOL. METHODS: The authors prospectively studied 96 patients with ALS using several instruments, including the McGill Quality of Life (MQOL) instrument, the Idler Index of Religiosity, the Sickness Impact Profile (SIP)/ALS-19, and several measures of strength and physical function. RESULTS: QOL as assessed by patients (MQOL single item score) did not correlate with measures of physical function and strength, but correlated with the total MQOL score (p < 0.0005), the psychological and existential subscores of MQOL (p < 0. 0005), the support subscore of MQOL (p = 0.001), and the total Idler score (p = 0.001). In contrast, correlations between SIP/ALS-19 and these measures were not significant, although SIP/ALS-19 correlated with measures of physical function and strength. CONCLUSIONS: QOL, as assessed by the patient with ALS, does not correlate with measures of strength and physical function, but appears to depend on psychological and existential factors, and thus may be measured well by the MQOL scale. Spiritual factors and support systems appear to play roles as well. SIP/ALS-19 is a good measure of physical function, but not of overall QOL.

Activities of Daily Living↗
PubMed2000

Improved outcome in childhood B-cell lymphoma with the intensified French LMB protocol.

BACKGROUND: During the last 20 years, 120 children with B cell lymphoma were treated at the National Pediatric Hematology/Oncology Center of Israel. Until 1986, 63 patients received an institutional protocol (BMC), and thereafter 57 patients received a modified French LMB protocol. We report the results of a retrospective analysis comparing the results of these two protocols. PROCEDURE: Patient characteristics were similar in both groups except for stage of disease and lactate dehydrogenase (LDH) levels. Significantly more patients in the LMB group had higher stage disease, and the LDH levels also were higher (<600 microg/ml). RESULTS: Fifty-four of fifty-seven children on the modified LMB protocol are alive, disease-free, with an overall event-free survival of 94% (median follow-up of 73 months). Event-free survival for stages I, II, and III patients is 100%, and for stage IV 77%, whereas the overall event-free survival was 58% among 63 children treated previously, and for stage IV patients only 10%. Severe marrow suppression and neutropenic enterocolitis were the major complications of this intensive protocol. CONCLUSIONS: Intensive chemotherapy with a modified LMB protocol and modern supportive care result in a high cure rate of childhood B cell lymphoma even in patients with advanced disease.

Adolescent↗
PubMed2000

Heparin interference with reverse transcriptase polymerase chain reaction of RNA extracted from lungs after ischemia-reperfusion.

The reverse transcriptase polymerase chain reaction (RT-PCR) is a rapid and sensitive method for detecting gene expression. However, when we used this technique to study gene expression of cytokines in ischemic and ex-vivo-reperfused rat lungs as a model for transplantation, significant inhibition of RT-PCR reaction was observed. To optimize RT-PCR conditions, RNA was extracted from rat lungs after flushing, preservation, and reperfusion. RNA was further purified and PCR conditions were modified with various strategies. We found that heparinase I pretreatment completely overcame the inhibitory effects of RT-PCR using RNA extracted from lung tissues after ischemia-reperfusion. With this treatment, a dramatic increase in tumor necrosis factor-a (TNF-a) mRNA was revealed from lung tissues after ischemia-reperfusion. This result suggests that residual heparin in lung tissue interferes with RT-PCR. Because heparinization is routinely used during clinical and experimental organ transplantation, we recommend the treatment of RNA samples with heparinase prior to RT-PCR.

Animals↗
PubMed2000

Raffinose improves the function of rat pulmonary grafts stored for twenty-four hours in low-potassium dextran solution.

OBJECTIVES: The perfect strategy for pulmonary graft preservation remains elusive. Experimental work supports the use of perfusates, such as Euro-Collins, University of Wisconsin, and low-potassium dextran solutions. We use low-potassium dextran solution in our clinical program, but we aim for continued improvement. The trisaccharide raffinose has been shown to be responsible for the efficacy of University of Wisconsin perfusate in lung preservation. Raffinose is superior to a variety of other saccharides for this purpose. We tested the hypothesis that the addition of raffinose to low-potassium dextran solution might further improve graft function. METHODS: In a randomized blinded study with a rat left lung transplant model, donor lungs were flushed with either standard low-potassium dextran solution or low-potassium dextran solution modified by the addition of 30 mmol/L raffinose (n = 5 for each group). Alprostadil (prostaglandin E(1), 500 microg/L) was added to the perfusates in accordance with our clinical practice. Grafts were stored inflated at 4 degrees C for 24 hours. After transplantation, recipients were ventilated with a fraction of inspired oxygen of 1 and a positive end-expiratory pressure of 2 cm H(2)O. Graft function was evaluated by measuring oxygenation at 2 hours after graft reperfusion, peak airway pressure throughout the reperfusion period, and the wet/dry lung weight ratio. RESULTS: The group receiving low-potassium dextran solution with raffinose demonstrated significantly higher oxygenation (oxygen tension, 370 +/- 45 mm Hg vs 150 +/- 64 mm Hg; P =.0025), lower peak airway pressures at 2 hours after lung reperfusion (11 +/- 2.7 mm Hg vs 16 +/- 2.4 mm Hg; P <.001), and a lower wet/dry weight ratio (4.7 +/- 1.26 vs 11 +/- 5. 0; P =.017). CONCLUSION: Modification of low-potassium dextran solution with the trisaccharide raffinose resulted in a significant improvement in graft function in this model and merits further evaluation with respect to the mechanisms involved.

Animals↗
PubMed2000

Prevention of latex allergy by selection of low-allergen gloves.

BACKGROUND: In recent years the prevalence of type I allergy to latex has continuously increased, in particular among healthcare workers, to about 10%. While most forms of type I allergy caused by other environmental allergens can be treated by pharmacotherapy or specific immunotherapy, minimizing exposure to latex proteins may represent an effective preventive measure for latex allergy. OBJECTIVE: To investigate whether it is possible to select by in vitro and in vivo testing low-allergen latex gloves for prevention of latex allergy. METHODS: We obtained separate extracts by standard aqueous extraction from the inner and outer surfaces of 15 different commonly used (10 examination, five surgical) glove brands. The extracts were analysed by quantitative (bicinchoninic protein assay, immunoglobulin [Ig] E-ELISA, ELISA competition) and qualitative (SDS-PAGE, silver staining, IgE immunoblotting) methods for their protein and allergen contents. In addition, the glove extracts were analysed for their capacity to induce basophil histamine release and immediate skin reactions. RESULTS: Extracts from different glove brands contained cross-reactive IgE epitopes. However, IgE binding studies, basophil histamine release and skin testing showed that different glove brands and their inner and outer surfaces contained widely varying protein and allergen contents. While the determination of total protein contents was not sufficient to identify low-allergen gloves, IgE measurements, basophil histamine release and skin testing were in good agreement and allowed to select low-allergen products. CONCLUSION: We suggest the use of low-allergen latex products identified by IgE binding, basophil histamine release assays and skin testing as a feasible preventive measure for latex allergy.

Adolescent↗
PubMed2000

Effect of digoxin on circadian blood pressure values in patients with congestive heart failure.

BACKGROUND: The aim of the study was to investigate the effect of chronic digoxin treatment on circadian blood pressure profile in normotensive patients with mild congestive heart failure. METHODS: In a randomized double-blind, placebo-controlled cross-over protocol, 12 normotensive patients with mild congestive heart failure took digoxin or placebo for a total of 7 days. Automatic 24-h ambulatory blood pressure measurements were carried out at day 7, of either digoxin or placebo. RESULTS: Diastolic blood pressure significantly decreased and systolic blood pressure significantly increased during overnight sleep in the digoxin phase compared to placebo. Digoxin had no effect on either systolic or diastolic blood pressure during daytime. Heart rate decreased in the overnight sleeping phase but did not differ significantly between placebo and digoxin phase. CONCLUSIONS: Digoxin significantly decreases diastolic blood pressure during overnight sleep in patients with congestive heart failure. This effect is likely to be caused by reduction of sympathetic activity or increase of parasympathetic activity. Increase of systolic blood pressure during sleep is probably caused by the positive inotropic effect of the drug.

Aged↗
PubMed2000

Effects of phospholipase A2, free fatty acids and 2-lysolecithin on the crystallization of cholesterol in gallbladder bile.

BACKGROUND: Phospholipase A2 (PLA2) and its enzymatic products free fatty acids (FFAs) and 2-lysolecithin are physiological constituents of bile. Their role in the crystallization of cholesterol in gallbladder bile of patients with cholesterol gallstones is still controversial. DESIGN: To clarify this issue we evaluated the activity of PLA2 and the concentration and pattern of FFAs in the gallbladder bile of cholesterol stone patients. We furthermore added PLA2, FFAs and 2-lysolecithin to isotropic gallbladder bile, determined the crystal observation time (COT) and counted the cholesterol crystals in a crystal growth assay for up to 21 days. RESULTS: A PLA2 activity of 1.8 +/- 1.2 U L(-1) and total FFA concentrations of 1.32 +/- 0.71 mmol L(-1) were determined. After incubation of bile for 24 h at 37 degrees C total FFAs increased to 2.72 +/- 1.29 mmol L(-1) (P<0.005). Biliary saturated and unsaturated FFAs were found in equal proportions before and after incubation, pointing to an additional presence of lipases other than PLA2. A COTof 1 day was observed in all gallbladder biles and increased to 1.7 +/- 0.5 days after addition of 5 U L(-1) of PLA2 (P<0.01). An even higher COT of 2.5 +/- 0.8 days was seen after addition of 5 mmol L(-1) of a 'biliary' mixture of FFAs (P<0.005) but the COT remained unchanged after addition of 5 mmol L(-1) of 2-lysolecithin. However, in the crystal growth assay in gallbladder bile addition of 5 U L(-1) of PLA2, of 5 mmol L(-1) of 'biliary' FFAs and of 5 mmol L(-1) of 2-lysolecithin decreased significantly the number of cholesterol crystals formed during follow-up. CONCLUSION: An elevated activity of PLA2 in gallbladder bile may counteract the formation of cholesterol crystals through increased formation of FFAs and 2-lysolecithin. However, regarding the comparatively low activity of PLA2 in gallbladder bile PLA2 seems to be of only minor pathophysiological importance in the formation of cholesterol gallstones.

Adult↗
PubMed2000

[Development and validation of a test for early diagnosis of dementia with differentiation from depression (TFDD)].

Psychometric tests used for the early detection of dementia often are seen as too difficult or too complex. Classical neuropsychologic tests were not developed for this purpose. Sensitivity and specificity to discriminate "healthy" vs. "ill" are low. For measuring both dementive and depressive symptoms, so far no test has been published. The objective of this study was to develop a sensitive and specific test for dementia that is easy to administer and to evaluate. Moreover, it should discriminate dementia from depressive pseudodementia. With respect to former studies, items were selected that recognized patients in the beginning of the disease. Additionally, depressive symptoms were rated. With the items for dementia, 88 patients with dementia of the Alzheimer type, 52 patients with depressive disorder and 37 healthy elderly controls were investigated. In this group of already diagnosed patients, the test reached a sensitivity and specificity of 100 percent (healthy elderly controls vs. patients with Alzheimer's disease: n = 125, U = 0, p < 0.001; patients with depressive disorder vs. patients with Alzheimer's disease: n = 140, U = 0, p < 0.001; healthy elderly controls vs. patients with depressive disorder: n = 89, U = 485.5, p < 0.001). For the dementia items, the inter-rater-reliability was rs = 0.996 (p < 0.001, n = 18), for the depression items it was rs = 0.753 (n = 18, p < 0.001). The test-retest-reliability was rs = 0.868 (p < 0.001, n = 35) for the dementia items and rs = 0.7 (n = 8, p < 0.05) for the depression items. These validation data will make the test useful for practitioners. Its ability to discriminate patients suffering from dementia of the Alzheimer type from healthy controls is comparable to tests consuming more time.

Aged↗
PubMed2000

Characterization of the neuroprotective effects of estrogens on hydrogen peroxide-induced cell death in hippocampal HT22 cells: time and dose-dependency.

Time and dose-dependency of the effects of estrogens (17-beta estradiol, estrone) and non-estrogenic steroids (progesterone, dexamethasone and methylprednisolone) on the toxicity of hydrogen peroxide were examined in mouse hippocampal HT22 cells. Hydrogen peroxide, an important intermediate of various disease-relevant oxidative stressors, induced cell death in HT22 cells in extracellular concentrations between 0.5 and 1.5 mM in a dose-dependent manner (EC50=0.95 mM). Regarding the underlying mechanisms of toxicity, incubation with hydrogen peroxide did not induce lipid peroxidation in living HT22 cells under these conditions. After preincubation with estrogens and non-estrogenic steroids for 22 hours, estrogen compounds protected the cells against hydrogen peroxide toxicity. Estrogens showed a maximal protective effect at 60-70% of hydrogen peroxide toxicity which diminished at higher and lower concentrations of the toxic challenge. Dose-dependency studies of estrogens revealed that concentrations of 1 microM already exerted a significant cytoprotective effect. Co- and postincubation with 17-beta estradiol and estrone also resulted in significant cell protection even if the estrogens were added 30 min after the initiation of the challenge with hydrogen peroxide. In contrast, preincubation with other steroids like progesterone, a physiological gonadal steroid, dexamethasone, a synthetic glucocorticoid and methylprednisolone, a glucocorticoid with radical scavenging properties, did not protect the cells against hydrogen peroxide toxicity but resulted in a dose-related decrease of HT22 cell survival in the course of the toxic challenge.

Animals↗
PubMed2000

Inhibition of angiotensin-converting enzyme by captopril: a novel approach to reduce ischemia-reperfusion injury after lung transplantation.

OBJECTIVES: Ischemia-reperfusion injury after lung transplantation involves the generation of free radicals. Captopril has been shown to be protective in models of ischemia-reperfusion injury in other organs by acting as a free radical scavenger. The purpose of this study was to assess the protective effects of captopril against ischemia-reperfusion injury and to evaluate the ability of captopril to scavenge free radicals and inhibit neutrophil activation in an experimental model of lung transplantation. METHODS: A rat single-lung transplant model was used. Donor lungs were flushed and preserved in low-potassium dextran-glucose solution with (n = 5) and without captopril (500 micromol/L; n = 5) for 18 hours at 4 degrees C and then transplanted and reperfused for 2 hours. At the conclusion of the 2-hour reperfusion period, arterial blood gases, blood pressure, and peak airway pressure were measured. Lung tissue biopsy specimens were obtained for assessment of wet/dry weight ratios, histology, and neutrophil sequestration (myeloperoxidase activity). Lipid peroxidation (F(2)-isoprostane assay) was analyzed from plasma samples and tissue lysates. RESULTS: The addition of captopril to the lung preservation solution significantly improved postreperfusion PO (2) (312 +/- 63.3 mm Hg vs 202 +/- 21.1 mm Hg; P =.006), peak airway pressure (11.4 +/- 1.1 cm H(2)O vs 15.6 +/- 1.5 cm H(2)O; P =.001), and wet/dry weight ratio (4.9 +/- 0.4 vs 15.8 +/- 10.9; P =.008). Blood pressures did not differ significantly between groups. No significant differences were seen in myeloperoxidase activity or F(2)-isoprostane levels. CONCLUSIONS: The use of captopril in the preservation solution ameliorates ischemia-reperfusion injury in transplanted lungs after an extended cold preservation period. The mechanisms by which captopril is protective remain elusive but do not appear to include inhibition of neutrophil sequestration or lipid peroxidation. This novel approach to ischemia-reperfusion injury may lead to improved lung function after transplantation and provide further insight into the pathogenesis of acute lung injury.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Vascular endothelial growth factor (VEGF) stimulates monocyte migration through endothelial monolayers via increased integrin expression.

Monocytes play an important role in collateral vessel formation (arteriogenesis) by attaching to activated endothelium and by invading the walls of innate collateral vessels where they produce growth factors. Previous studies have demonstrated that this process can be promoted by several chemokines and growth factors. In this study we examined the interaction between monocytes and endothelium under stimulation of the angiogenic agent vascular endothelial growth factor (VEGF). We report here the novel finding that VEGF stimulates the expression of the alphaL-, alphaM- and beta2-integrin monomers. In functional assays and by using neutralizing antibodies it was shown that VEGF stimulates adhesion of monocytes to human umbilical vein endothelial cells (HUVEC), and increased transmigration through endothelial monolayers is dependent on interaction of monocyte beta2-integrins with its endothelial counter ligand ICAM-1. Based on these in vitro data we hypothesize that the positive effect of VEGF on arteriogenesis may involve monocyte activation.

Antibodies, Monoclonal↗
PubMed2000

Prospective double-blind randomised study of a new regimen of pre-emptive analgesia for inguinal hernia repair: evaluation of postoperative pain course.

OBJECTIVE: To evaluate the effectiveness of a new regimen of pre-emptive analgesia on the development of postoperative pain after inguinal hernia repair. DESIGN: Prospective, double-blind, randomised study. SETTING: University Hospital, Germany. SUBJECTS: 70 consecutive patients who had primary unilateral inguinal hernia repairs. INTERVENTIONS: A new regimen of pre-emptive analgesia with bupivacaine that was infiltrated preoperatively, intraoperatively, and postoperatively was tested. The control group were given saline infiltrations at the same times. Pain was measured up to postoperative day 30 using the visual analogue scale (VAS), the verbal rating scale (VRS), and by recording patient-controlled use of ibuprofen suppositories. RESULTS: Pain was significantly less in the pre-emptive analgesia group than in the control group during the first 10 days postoperatively as assessed by VAS and VRS (p < 0.05). Analgesic consumption was also significantly reduced in the pre-emptive analgesia group (p < 0.05). Multivariate analysis showed that bupivacaine infiltration (pre-emptive analgesia) was associated with significantly less postoperative pain (p < 0.0001). CONCLUSION: This regimen of pre-emptive analgesia is an effective and safe method of reducing postoperative pain and analgesic consumption after inguinal hernia repair.

Adult↗
PubMed2000

Cell death in human lung transplantation: apoptosis induction in human lungs during ischemia and after transplantation.

OBJECTIVE: To examine the presence and extent of apoptosis as well as the affected cell types in human lung tissue before, during, and after transplantation. SUMMARY BACKGROUND DATA: Apoptosis has been described in various human and animal models of ischemia-reperfusion injury, including heart, liver, and kidney, but not in lungs. Therefore, the presence of apoptosis and its role in human lungs after transplantation is not clear. METHODS: Lung tissue biopsies were obtained from 20 consecutive human lungs for transplantation after cold ischemic preservation (1-5 hours), after warm ischemia time (during implantation), and 30, 60, and 120 minutes after graft reperfusion. To detect and quantify apoptosis, fluorescent in situ end labeling of DNA fragments (TUNEL assay) was used. Electron microscopy was performed to verify the morphologic changes consistent with apoptosis and to identify the cell types, which were lost by apoptosis. RESULTS: Almost no evidence of apoptosis was found in specimens after immediate cold and warm ischemic periods. Significant increases in the numbers of cells undergoing apoptosis were observed after graft reperfusion in a time-dependent manner. The mean fraction of apoptotic cells at 30, 60, and 120 minutes after graft reperfusion were 16.6%, 22.1%, and 34.9% of total cells, respectively. Most of the apoptotic cells appeared to be alveolar type II pneumocytes, as confirmed by electron microscopy. CONCLUSIONS: Programmed cell death (apoptosis) appears to be a significant type of cell loss in human lungs after transplantation, and this may contribute to ischemia-reperfusion injury during the early phase of graft reperfusion. This cell loss might be responsible for severe organ dysfunction, which is seen in 20% of patients after lung transplantation. Therefore, this work is of importance to surgeons for the future development of interventions to prevent cell death in transplantation.

Adolescent↗
PubMed2000

Effect of astroglial cells on hypoxia-induced permeability in PBMEC cells.

An in vitro model of the blood-brain barrier (BBB), consisting of porcine brain-derived microvascular endothelial cells (PBMEC), was used to evaluate the effect of astrocytes in the BBB disruption during hypoxia. Hypoxia-induced hyperpermeability was decreased significantly in a coculture model of astroglia cells, either astrocytes or C6 glioma cells, with PBMEC and, to the same extent, when glia cell-conditioned medium was used. Corresponding to effects on hypoxia-induced hyperpermeability, astrocyte- and C6 cell-conditioned medium diminished hypoxia-induced vascular endothelial growth factor (VEGF) mRNA and protein expression, which recently was shown to be responsible for hypoxia-induced permeability changes in vitro. The effect on hypoxia-induced hyperpermeability and VEGF expression was specific for astroglia cells because conditioned medium from bovine smooth muscle cells (BSMC) did not show any effect. Immunocytochemistry revealed that 24 h of hypoxia disrupted the continuity of the tight junction protein, zonula occludens-1 (ZO-1), which lines the cytoplasmic face of intact tight junctions. These changes were prevented when hypoxia was performed in glia cell-conditioned medium. Results suggest that astrocytes protect the BBB from hypoxia-induced paracellular permeability changes by decreasing hypoxia-induced VEGF expression in microvascular endothelial cells.

Animals↗
PubMed2000

A novel cell culture model for studying ischemia-reperfusion injury in lung transplantation.

Many cell culture models have been developed to study ischemia-reperfusion injury; however, none is specific to the conditions of lung preservation and transplantation. The objective of this study was to design a cell culture model that mimics clinical lung transplantation, in which preservation is aerobic and hypothermic. A549 cells, a human pulmonary epithelial cell line, were preserved in 100% O(2) at 4 degrees C for varying periods in low-potassium dextran glucose solution, simulating ischemia, followed by the introduction of warm (37 degrees C) DMEM plus 10% fetal bovine serum to simulate reperfusion. Cultures were assayed for cell attachment and viability. Sequential extension of ischemic times to 24 h showed a time-dependent loss of cells. There was a further decrease in cell number after simulated reperfusion. Cell detachment was due mainly to cell death, as determined by cell viability. The effects of chemical components such as dextran 40 and calcium in the preservation solution and various preservation gas mixtures were examined by use of this model system. With its design and validation, this model could be used to study mechanisms related to ischemia-reperfusion injury at the cellular and molecular level.

Cell Adhesion↗
PubMed2000

Targeting the angiotensin system in posttransplant airway obliteration: the antifibrotic effect of angiotensin converting enzyme inhibition.

The angiotensin system plays a role in the pathogenesis of fibrotic diseases. We used a rat heterotopic tracheal transplant model of bronchiolitis obliterans (BO) to examine the role of angiotensin converting enzyme (ACE) in development of the fibroproliferative lesion of BO. Isograft and allograft tracheal transplants were performed. Allograft rats received either no treatment (control) or captopril (100 mg/kg/d) in their drinking water. The drug treatment given to the recipient rats was begun 5 days before transplantation, on postoperative Day 1, or on postoperative Day 5. The treatment was continued until postoperative Day 21, when tracheal specimens were harvested and subjected to histologic, immunohistologic, and morphometric analyses. We noted heavy staining for ACE in the obliterated portion of the tracheas of allograft control animals. This area was not present in nontransplanted or isograft tracheas. Captopril administration begun 5 d before transplantation and on postoperative Day 1 resulted in a significant attenuation in the percent airway obliteration (45% and 26%, respectively) as compared with that in control allografts (83%; p < 0.05). This study demonstrates the presence of ACE in the fibroproliferative lesion in a rat model of BO, and shows that inhibition of ACE can limit development of airway obliteration.

Angiotensin-Converting Enzyme Inhibitors↗