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J D Cooper

Publications and source records attributed to J D Cooper.

At least 73 records · Page 4Linked to original sources
PubMed1998

Ex vivo liposome-mediated gene transfer to lung isografts.

OBJECTIVE: Gene therapy is a promising strategy to modify ischemia-reperfusion injury and rejection after transplantation. We evaluated variables that may affect ex vivo gene transfer to rat lung isografts. METHODS: Left lungs were harvested and perfused via the pulmonary vein with chloramphenicol acetyltransferase complementary deoxyribonucleic acid complexed with cationic liposomes. Several variables were examined: (1) Influence of temperature: In group I (n = 4), grafts were stored for 4 hours at 23 degrees C and transplanted. Chloramphenicol acetyltransferase activity was assessed on postoperative day 2. In groups II and III (n = 4), grafts were stored at 10 degrees and 4 degrees C, respectively. Arterial oxygen tension and inflammatory infiltrate were also determined. (2) Influence of storage time: Grafts were preserved at 10 degrees C for 1, 2, 3, 4 (n = 4), and 10 hours (n = 5). chloramphenicol acetyltransferase activity was assessed on postoperative day 2. (3) Rapidity and duration of transgene expression: Grafts were preserved at 10 degrees C for 1 hour and then transplanted. Chloramphenicol acetyltransferase activity was assessed 2, 4, 6, 12, and 24 hours and 2, 7, 14, 21, and 28 days after implantation. RESULTS: Chloramphenicol acetyltransferase expression was apparently less in lungs transfected at 4 degrees C than in those transfected at 10 degrees and 23 degrees C. Storage for 1 hour at 10 degrees C was sufficient to yield significant expression. Increasing the exposure time to 10 hours did not increase toxicity. There were no differences in arterial oxygen tension between transfected and nontransfected lungs. Chloramphenicol acetyltransferase expression was detected for at least 28 days. CONCLUSION: Ex vivo liposome-mediated transfection of lung isografts can be achieved after a short time of cold storage, with minimal toxicity.

Animals↗
PubMed1998

Increased expression of HDJ-2 (heat shock protein 40) and heat shock protein 70 in biopsy specimens of transplanted human lungs.

BACKGROUND: Heat shock proteins are expressed during several forms of stress and inflammation. This study was done to determine whether the expression of heat shock protein HDJ-2 (heat shock protein 40), heat shock protein 60, and heat shock protein 70 are increased during rejection in human pulmonary allografts. METHODS: Thirty-five transbronchial biopsy specimens were obtained from adult lung transplant recipients. Histologic analysis and assessment of heat shock protein HDJ-2, heat shock protein 60, and heat shock protein 70 mRNA expression was performed. Total RNA was extracted, reverse transcribed, and amplified by polymerase chain reaction with oligonucleotide primers specific for the heat shock proteins. The identity of the amplified message was verified by Southern blot and slot blot analysis. RESULTS: The expression of heat shock protein HDJ-2 was significantly higher in samples from lung transplant recipients undergoing rejection when compared with recipients without rejection or infection. Heat shock protein 70 expression was also increased in rejection. Expression of heat shock protein 60 did not show any increase in recipients with no evidence of rejection and infection or transplant recipients with rejection or infection. Serial analysis of heat shock protein HDJ-2 and heat shock protein 70 obtained in biopsy specimens during and after rejection showed a decrease of heat shock protein HDJ-2 and heat shock protein 70 expression after resolution of lung rejection. CONCLUSION: Our data demonstrate that the expression of heat shock protein HDJ-2 and heat shock protein 70 increases during lung rejection. However, only heat shock protein HDJ-2 was able to differentiate between rejection and infection. Measurement of heat shock protein HDJ-2 in transbronchial biopsy specimens may assist in the differential diagnosis between rejection and infection in lung transplant recipients.

Carrier Proteins↗
PubMed1998

Vasoactive intestinal peptide ameliorates reperfusion injury in rat lung transplantation.

BACKGROUND: Vasoactive intestinal peptide (VIP) has been reported to have some properties that provide protection from lung injury. Furthermore, its protective effect in cold storage of donor lungs has been confirmed. We examined its effect and the timing of administration in an in vivo rat lung transplantation model. METHODS: All lungs were flushed with low-potassium dextran-1% glucose solution, and orthotopic left lung transplantations were performed. Rats were divided into four groups (n = 6). Group I received no preservation or storage. Groups II, III, and IV grafts were stored for 18 hours at 4 degrees C. Group II received no VIP. Group III received VIP (0.1 g/ml) via the flush solution. Group IV recipients received VIP (3 microg/kg) intravenously just after reperfusion. Twenty-four hours after transplantation, the right main pulmonary artery and right main bronchus were ligated, and the rats were ventilated with 100% O2 for 5 minutes. Mean pulmonary arterial pressure, peak airway pressure, blood gas analysis, serum lipid peroxide level, tissue myeloperoxidase activity, and wet-dry weight ratio were measured. RESULTS: The partial O2 tension values of groups III and IV were better than group II (groups II, III, and IV: 147.4 +/- 71.4, 402.1 +/- 64.8, 373.4 +/- 81.0 mm Hg; p < 0.05). Peak airway pressure was lower in groups III and IV than in group II (groups II, III, and IV: 19.7 +/- 0.8, 16.7 +/- 0.9. and 16.3 +/- 1.0 mm Hg; p < 0.05). Mean pulmonary arterial pressure in group III was lower than group II (groups II and III: 36.3 +/- 3.0 and 22.1 +/- 2.2 mm Hg; p < 0.01). Wet-dry weight ratio in group III was lower than in groups II and IV (group II, III, and IV: 5.2 +/- 0.2, 4.4 +/- 0.2, and 5.2 +/- 0.3; II vs III; p < 0.05, III vs IV; p < 0.01). Serum lipid peroxide levels in groups III and IV were significantly lower (groups II, III, and IV: 2.643 +/- 0.913, 0.455 +/- 0.147, and 0.325 +/- 0.124 nmol/ml; p < 0.01). CONCLUSION: VIP ameliorates reperfusion injury in an in vivo rat lung transplantation model. Either administration of VIP via the flush solution or systemically just after reperfusion was associated with improved pulmonary function.

Airway Resistance↗
PubMed1998

Delayed administration of low-dose NPC18915 ameliorates lung ischemia-reperfusion injury.

BACKGROUND: NPC18915, a member of new antiinflammatory agent called nactins (neutrophil activation inhibitors), has been shown to reduce reperfusion injury in rat lung transplantation at high dosage. In vitro studies have demonstrated effectiveness of this compound even at low dosage. We hypothesized that this compound ameliorates lung ischemia reperfusion injury even at low dosage levels if administration is optimally timed. The aim of this study was to determine the efficacy and the best timing for administration of low-dose NPC18915. METHODS: Forty syngeneic rat left lung transplantations were performed. All isografts were flushed with low-potassium dextran-1% glucose solution 20 ml and preserved for 18 hours at 4 degrees C. Animals were divided into four groups. Group I animals (n = 10) served as control subjects. In groups II (n = 10), III (n = 10), and IV (n = 10), NPC18915 (0.04 mg) was added to the flush solution and was administered intravenously (0.4 mg/kg) immediately before reperfusion (group II) and 60 minutes (group III) and 120 minutes (group IV) after reperfusion. Pulmonary function was assessed 24 hours after reperfusion. RESULTS: In group III, oxygenation improved in comparison to group I (247.2 +/- 59.8 versus 76.6 +/- 16.0 mm Hg, p < 0.002). Wet-to-dry weight ratio and graft myeloperoxidase activity were significantly improved (group III versus group I, 6.02 +/- 0.21 versus 7.19 +/- 0.41, p = 0.013) (group III versus group I, 0.093 +/- 0.019 versus 0.207 +/- 0.023 delta optical density/min/mg, p < 0.002). There were no significant differences in CD11b expression. CONCLUSION: These data suggest that delayed administration of NPC18915, 60 minutes after reperfusion, dramatically improves pulmonary graft function.

Animals↗
PubMed1998

Heat shock pretreatment protects pulmonary isografts from subsequent ischemia-reperfusion injury.

BACKGROUND: Heat shock has been associated with the acquisition of tolerance to a wide variety of stressful conditions, including ischemia. This is partly mediated by the production of various heat shock proteins (HSP), including HSP70. One novel approach to the reduction of ischemia-reperfusion injury after lung transplantation is the induction of HSP70 by heat pretreatment of the donor. The purpose of this study was to investigate the feasibility of this approach in an animal model of lung transplantation. METHODS: Animals were divided into six main groups, with groups I to III representing transplanted animals: In groups I and II, donor animals were anesthetized and then underwent heat stress 6 and 12 hours before organ harvest, respectively. Control animals underwent general anesthesia but no heat stress. After harvest, left lungs from groups I to III were preserved for 18 hours at 40 degrees C and then implanted into isogeneic recipients, which were killed 24 hours after reperfusion to assess graft function. Group IV and V animals underwent heat stress followed by a recovery period of 6 and 12 hours, respectively. Lungs were collected both at the time of harvest (right lungs) and after 18 hours of cold preservation (left lungs). Group VI served as nontransplanted controls. Groups IV to VI did not undergo lung transplantation. RESULTS: At the time of harvest but before implantation, HSP70 was significantly increased in heat-shocked nontransplanted donor lungs (groups IV and V) compared with group VI controls. After 18 hours of cold preservation, HSP70 levels were higher in group IV compared with group V and group VI controls. At 24 hours after reperfusion, mean arterial oxygenation was significantly higher in group I compared with group II and group III controls (290.25+/-24.5 vs 154.5+/-23.9 and 119.6+/-11.3 mm Hg, respectively; P < .001). Myeloperoxidase activity was improved in group I compared with group III controls (0.048+/-0.018 vs 0.137+/-0.036 deltaOD/mg/min, respectively; P < .05). The wet/dry weight ratio was also improved in group I compared with group III controls (6.2+/-0.3 vs. 7.8+/-0.4, respectively; P < .05). CONCLUSIONS: Heat pretreatment of the donor 6 hours before harvest results in increased synthesis of HSP70, which offers a dramatic protective effect against subsequent ischemia-reperfusion injury in the lung isograft.

Animals↗
PubMed1997

Simultaneous determination of lamotrigine and its glucuronide and methylated metabolites in human plasma by automated sequential trace enrichment of dialysates and gradient high-performance liquid chromatography.

The use of the system, automated sequential trace enrichment of dialysates (ASTED), to prepare plasma samples for the estimation of lamotrigine, its glucuronide and methylated metabolites in plasma prior to gradient high-performance liquid chromatography (HPLC) is described. Using this technique the procedure was observed to be specific for all three compounds and linear over the range 0.04 to 10 microg/ml for lamotrigine and the glucuronide metabolite and 2 to 500 ng/ml for the methylated metabolite. The within-run precision (C.V.) at four different supplemented plasma lamotrigine concentrations of 0.04, 0.10, 2.5 and 10.0 microg/ml was 6.21, 5.17, 1.29 and 0.73%, respectively, and the between-run precision (C.V.) estimated to be 13.49, 6.08, 1.95 and 1.78%, respectively. The overall accuracy (% bias) of the procedure was estimated to be 12.50, 0.00, 2.80 and 1.80%, respectively. The glucuronide and methylated metabolites in plasma showed similar assay performance.

Anticonvulsants↗
PubMed1997

Development of an assay for the simultaneous determination of sildenafil (Viagra) and its metabolite (UK-103,320) using automated sequential trace enrichment of dialysates and high-performance liquid chromatography.

The development of the ASTED (automated sequential trace enrichment of dialysates) system to prepare plasma samples prior to high-performance liquid chromatography (HPLC) of sildenafil and its demethylated metabolite (UK-103,320) is described. Investigations to elucidate potential pitfalls of the ASTED on-line sample preparation system prior to separation of the analytes by HPLC are presented. The procedure is shown to be selective for sildenafil and UK-103,320, and linear over the range 1.00-250 ng/ml. The intra-batch imprecision (C.V.) of the method at plasma analyte concentrations of 1.00, 5.00, 50.0 and 200 ng/ml was 11.2, 3.10, 1.50, and 1.30%, respectively, and the corresponding inter-batch imprecision was estimated to be 13.5, 7.09, 3.69, and 5.43%. At these plasma analyte concentrations the overall inaccuracy (% bias) of the procedure ranged from 3.6 to 8.4%. The method showed similar assay performance for the estimation of the metabolite, UK-103,320. The application of the assay to a pharmacokinetic investigation during a clinical study is presented.

Chromatography, High Pressure Liquid↗
PubMed1997

Absence of p75NTR causes increased basal forebrain cholinergic neuron size, choline acetyltransferase activity, and target innervation.

Emerging evidence suggests that the p75 neurotrophin receptor (p75NTR) mediates cell death; however, it is not known whether p75NTR negatively regulates other neuronal phenotypes. We found that mice null for p75NTR displayed highly significant increases in the size of basal forebrain cholinergic neurons, including those that are TrkA-positive. Cholinergic hippocampal target innervation also was increased significantly. Activity of the cholinergic neurotransmitter synthetic enzyme choline acetyltransferase (ChAT) was increased in both the medial septum and hippocampus. Upregulation of these cholinergic features was not associated with increased basal forebrain or hippocampal target NGF levels. In contrast, striatal cholinergic neurons, which do not express p75NTR, showed no difference in neuronal number, size, or ChAT activity between wild-type and p75NTR null mutant mice. These findings indicate that p75NTR negatively regulates cholinergic neuronal phenotype of the basal forebrain cholinergic neurons, including cell size, target innervation, and neurotransmitter synthesis.

Animals↗
PubMed1997

Use of the ASTED system to determine L-NG-monomethylarginine (546C88) in human plasma by pre-column o-phthalaldehyde derivatisation and high-performance liquid chromatography.

The use of the system automated sequential trace enrichment of dialysates (ASTED), to prepare plasma samples for the estimation of L-NG-monomethylarginine (546C88) by pre-column o-phthalaldehyde-2-mercaptoethanol derivatisation and HPLC is described. Calibration is achieved using purified albumin as a substitute matrix for plasma. Using this technique the procedure was observed to be specific for 546C88 and linear over the range 0.10 to 50.0 mumol/l. The within-run imprecision (C.V.) at four different spiked plasma 546C88 concentrations of 0.10, 1.0, 8.0 and 40.0 mumol/l was 6.48, 2.55, 2.79 and 3.37%, respectively, and the between-run imprecision (C.V.) estimated to be 8.50, 1.80, 2.10 and 3.30%, respectively, for the same spiked 546C88 concentrations. The overall accuracy (% bias) of the procedure using an albumin matrix for calibration was estimated to be -2.50, -5.25, -3.56, -3.53%, respectively, and the recovery of 546C88 from six different spiked plasma samples estimated to be 99.1 +/- 1.4%.

Chromatography, High Pressure Liquid↗
PubMed1997

Determination of vitamin E in human plasma by high-performance liquid chromatography.

The use of selective protein precipitation to enhance the recovery of vitamin E from plasma, by minimising binding with very-low-density lipoproteins, is reported. The procedure employed treatment of plasma with magnesium chloride and tungstate, followed by methanol protein precipitation. Separation of vitamin E was performed using reversed-phase high-performance liquid chromatography of the methanol extracts with subsequent UV detection of the compound. Using this technique the procedure was observed to be specific for vitamin E and linear over the range 1.0 to 40.0 micrograms/ml. The within-run imprecision (C.V.) at three different supplemented plasma vitamin E concentrations of 5.0, 10.0 and 20.0 micrograms/ml was 4.51, 3.33 and 2.58%, respectively, and the between-run imprecision (C.V.) estimated to be 5.19, 3.69 and 3.67%, respectively. With the same supplemented plasma vitamin E concentrations, the overall accuracy (bias) of the procedure, using an albumin matrix for calibration, was estimated to be 6.0, -5.0 and -3.5%, respectively, and the recovery of vitamin E from six different spiked plasma samples estimated to be 98.2 +/- 2.6%.

Chromatography, High Pressure Liquid↗
PubMed1997

Retrieval by other procurement teams provides favorable lung transplantation outcome.

BACKGROUND: During the last 4 years, we have increasingly used lungs retrieved by other procurement teams. We therefore investigated whether the use of those lungs affected the outcome of lung transplantation. METHODS: We analyzed the results of 159 consecutive lung transplantations performed at our institution between July 1, 1992, and December 31, 1995. The transplants were divided into three groups: distant donor lungs retrieved by our team (DB group, n = 68); distant donor lungs retrieved by other teams (DX group, n = 46); and local donor lungs retrieved by our team (LB group, n = 44). One transplantation with a local donor lung retrieved by another team was excluded from the analysis. RESULTS: No significant differences were noted between the three groups in alveolar-arterial oxygen gradient immediately after transplantation (DB group, 359 +/- 18 mm Hg; DX group, 329 +/- 23 mm Hg; LB group, 327 +/- 20 mm Hg) and at 24 hours; days on ventilator; days in the intensive care unit; length of hospital stay; 30-day mortality; and actuarial 1-year survival (DB group, 81%; DX group, 87%; LB group, 89%). CONCLUSIONS: The use of donor lungs retrieved by other teams achieves an equivalently satisfactory outcome after lung transplantation as lungs retrieved by our team.

Adult↗
PubMed1997

Inhaled nitric oxide at the time of harvest improves early lung allograft function.

BACKGROUND: Inhalation of nitric oxide (NO) has been shown to have beneficial effects on a variety of acute lung injuries, including lung allograft reperfusion injury. The purpose of the present study was to investigate the effects of inhaled NO at the time of harvest on function of canine left lung allografts after transplantation. METHODS: Ten dogs underwent left lung allotransplantation. Donor lungs were flushed with modified Euro-Collins solution and stored for 21 hours at 1 degree C. Immediately after transplantation, the contralateral main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamics and arterial blood gases (inspired oxygen fraction, 1.0) were assessed intermittently for 6 hours prior to sacrifice. Allograft myeloperoxidase activity and wet to dry weight ratio were assessed. Donor animals were divided into two groups. Group I animals (n = 5) received no NO. In group II (n = 5), donors received inhaled NO (60 ppm) at the time of harvest. RESULTS: Pulmonary vascular resistance decreased to 79.6% of baseline because of inhalation of 60 ppm NO in group II donor animals. Thiobarbituric acid-reactive materials were reduced during the storage period in group II, a finding suggesting less oxidant injury during storage in donor lungs treated with NO. Throughout the 6-hour assessment, oxygenation in group II was superior to that in group I (p < 0.05). At 360 minutes of assessment, mean arterial oxygen tension in groups I and II was 88.9 +/- 11.4 mm Hg and 169.1 +/- 33.0 mm Hg, respectively. Myeloperoxidase activity was significantly decreased in group II (p < 0.05), data indicating reduced neutrophil sequestration. Wet to dry weight ratio was significantly lower in group II. CONCLUSIONS: These data suggest that inhaled NO at the time of harvest improves early function of preserved lung allografts by attenuating oxidant injury during storage and subsequent neutrophil sequestration.

Administration, Inhalation↗
PubMed1997

Ex vivo adenoviral-mediated gene transfer to lung isografts during cold preservation.

BACKGROUND: Although whole-organ gene transfer has been reported in heart and liver transplant models, it has not been well characterized in lung grafts. The aim of this study was to determine the feasibility of ex vivo gene transfer to rat lung isografts during cold preservation using an adenoviral vector. METHODS: F344 rats, divided into four groups, underwent orthotopic left lung transplantation. In group I, lung grafts were flushed with adenovirus carrying the beta-galactosidase gene. After storage at 10 degrees C, grafts were implanted in recipient animals. Group II underwent the same procedure but graft storage was at 4 degrees C. Groups III (10 degrees C) and IV (4 degrees C) served as controls. On postoperative day 5, recipients were sacrificed, and native and transplanted lungs were examined. RESULTS: In group I, all animals showed successful, albeit patchy, gene expression. This occurred in 2 of 4 animals in group II, the other 2 showing no expression. Transduced cells were consistent morphologically with endothelial cells and pneumocytes. A minimal mononuclear inflammatory infiltrate was present. Control groups showed no transduction. CONCLUSIONS: It is feasible to perform ex vivo adenoviral-mediated gene transfer to rat lung isografts during cold preservation.

Adenoviridae↗
PubMed1997

Improvement in staging of esophageal cancer with the addition of positron emission tomography.

BACKGROUND: Positron emission tomography with the glucose analogue 2-[18F]fluoro-2-deoxy-D-glucose (FDG) has been used to detect and stage a variety of malignancies. We hypothesized that FDG-positron emission tomography would improve staging of patients with esophageal cancer and thereby facilitate selection of candidates for resection. METHODS: Fifty-eight patients (42 men and 16 women) with biopsy-proven esophageal cancer were evaluated with both FDG-positron emission tomography and computed tomography. RESULTS: In all but 2 patients, increased FDG uptake was identified at the site of the primary tumor. Six patients were not operative candidates. Seventeen patients were not candidates for resection because of metastatic disease. Positron emission tomography identified the metastatic disease in all 17 (12 of whom underwent confirmatory biopsy), whereas computed tomography was positive for metastases in only 5. The remaining 35 patients underwent surgical exploration, were judged to have resectable disease and had esophagectomy. Pathologic examination of resected specimens identified lymph node metastases in 21 patients. These nodes were detected by positron emission tomography in 11 patients and by computed tomography in 6. CONCLUSIONS: Positron emission tomography improved staging and facilitated selection of patients for operation by detecting distant disease not identified by computed tomography alone.

Adenocarcinoma↗
PubMed1997

Coronary artery bypass grafting after a bilateral lung volume reduction operation.

A 67-year-old man underwent coronary artery bypass grafting 31/2 months after a bilateral lung volume reduction operation for end-stage pulmonary emphysema. The principles of anesthetic management we have developed for use during volume reduction operations were applied with success in this individual and are described in detail. With the increasing application of this intervention as an alternative to lung transplantation, we anticipate further experience in the operative management of associated conditions after lung volume reduction operations.

Aged↗
PubMed1997

Liposome-mediated gene transfer to lung isografts.

OBJECTIVES: Our objective were to determine the feasibility, efficacy, and safety of in vivo and ex vivo liposome-mediated gene transfer to lung isografts. METHODS: Fischer rats were divided into three main groups: (1) Nontransplant setting: Liposome-chloramphenicol acetyl transferase cDNA was intravenously injected, and lungs were harvested at different time points: 2, 6, 12, and 24 hours; 2, 5, 8, and 21 days (n = 3). Chloramphenicol acetyl transferase activity was determined in lungs, hearts, livers, and kidneys. The distribution and type of transfected cells were evaluated by in situ hybridization. Lung toxicity was assessed by arterial oxygen tension, histology, and tumor necrosis factor-alpha levels. (2) In vivo graft transfection: Left lungs were transplanted 6 hours, 4 hours, and 15 minutes after intravenous injection and were assessed for chloramphenicol acetyl transferase activity and arterial oxygen tension on postoperative day 2. (3) Ex vivo graft transfection: Grafts were infused ex vivo with either 660 micrograms (n = 3) or 330 micrograms (n = 3) of DNA complexed to liposomes and stored at 10 degrees C for 4 hours. Chloramphenicol acetyl transferase activity was assessed 44 hours after transplantation. RESULTS: Transgene expression was detected in endothelial cells, macrophages, and interstitial cells. Chloramphenicol acetyl transferase activity was present as early as 2 hours, increased significantly between 6 hours and 8 days, and then decreased to minimal levels by 21 days. Chloramphenicol acetyl transferase activity was greatest in donor lungs and hearts and minimal in livers and kidneys. Arterial oxygen tension was normal in treated animals. Inflammation was minimal, and tumor necrosis factor-alpha levels increased only sevenfold in treated animals. CONCLUSION: In vivo and ex vivo liposome-mediated gene transfer to lung isografts allows significant transgene expression with minimal effects on graft function.

Animals↗
PubMed1997

Successful in vivo and ex vivo transfection of pulmonary artery segments in lung isografts.

OBJECTIVE: Gene transfer to lung grafts may be useful in ameliorating ischemia-reperfusion injury and rejection. Efficient gene transfection to the whole organ may prove problematic. Proximal pulmonary artery endothelial transfection might provide beneficial downstream effects on the whole graft. The aim of this study was to determine the feasibility of transfecting proximal pulmonary artery segments in lung isografts. METHODS: Male Fischer rats were divided into six groups. In vivo transfection: In group I (n = 7), a proximal segment of the left pulmonary artery was isolated and injected with saline solution by means of a catheter inserted through the right ventricle. After an exposure period of 20 minutes, clamps were removed and blood flow was restored. In group II (n = 7), the isolated arterial segments were injected with adenovirus carrying the Escherichia coli LacZ gene encoding for beta-galactosidase. Ex vivo transfection: In group III (n = 5), arterial segments were injected ex vivo with saline solution and in group IV (n = 5) with the adenovirus construct. In group V (n = 6), arteries were injected with saline solution and in group VI (n = 11) with liposome chloramphenicol acetyl transferase cDNA. In groups I to IV, animals were killed on postoperative day 3 and transgene expression was assessed by Bluo-Gal staining. In groups V and VI, animals were killed on postoperative day 2 and transgene expression was assessed by chloramphenicol acetyl transferase activity assay. RESULTS: Transgene expression was detected grossly and microscopically in endothelial and smooth muscle cells of pulmonary artery segments from all surviving animals of groups II and IV. In group VI, chloramphenicol acetyl transferase activity was significant in all assessed arterial segments. CONCLUSION: Significant transgene expression is observed in proximal pulmonary artery segments after both in vivo and ex vivo exposure.

Animals↗