The effect of low-potassium-dextran versus Euro-Collins solution for preservation of isolated type II pneumocytes.

Limited availability of donor organs is a major factor restricting the clinical application of lung transplantation. Improvements in preservation techniques are essential for prolonging storage time and improving lung function following transplantation. The present investigation used primary cultures of adult rat alveolar type II cells as a model for evaluating lung-preservation solutions. Type II cells were plated onto tissue-culture plastic at a density 5 x 10(5) cells/cm2 and maintained in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum (D10) for 40 hr. Cells were then exposed to Euro-Collins solution or a low-potassium-dextran solution (LPD). At designated time points, measurements of lactate-dehydrogenase (LDH) release, protein content, and incorporation of 3H-thymidine into cellular DNA were made. During 12 hr of "storage" at 37 degrees C, cells maintained in LPD released less LDH (14.3 +/- 1.2% of cellular total, mean +/- SEM, n = 5) than their counterparts stored in EC (20.6 +/- 1.6%, P less than 0.05). During the 36 hr following a 6-hr exposure to preservative solutions, LPD-treated cells incorporated more thymidine per mg of protein (2566 +/- 419.8 cpm/micrograms protein, mean +/- SEM, n = 6) compared with cells maintained continuously in D10 (1431 +/- 351, P less than 0.05). By contrast, cells exposed to EC incorporated less thymidine (82.2 +/- 62.8 cpm/micrograms protein) than either cells maintained in LPD or D10 (P less than 0.01 for each comparison). These results suggest that LPD solution is less cytotoxic than EC and that LPD enables higher levels of metabolic activity in recovering epithelial cells. In vitro cultures of type II epithelial cells are a useful model system for the study of lung preservation and posttransplantation lung injury.

The superiority of an extracellular fluid solution over Euro-Collins' solution for pulmonary preservation.

Limited donor supply is the major factor restricting the application of lung transplantation. A uniformly reliable method of lung preservation would improve donor organ availability. At present, Euro-Collins' solution, an intracellular fluid-type solution, is most widely used in organ preservation. However, we have previously shown that initial pulmonary flush with an extracellular-type solution (low-potassium dextran solution [LPD]) provided better pulmonary preservation than Euro-C. In the present study, we used an in vitro-ventilated, blood-perfused rabbit lung model to examine whether the mechanism for this improvement was related to the effect of LPD during pulmonary flush or its effect during storage. Rabbit lungs were harvested and stored after pulmonary flush with different solutions (group 1: 400 ml of LPD; group 2: 400 ml of Euro-C; group 4: 300 ml of Euro-C followed by 100 ml of LPD; n = 5 in each group). The lungs were then preserved at 10 degrees C for 18 hr and reperfused with fresh venous blood. After 10 min of reperfusion, lungs in group 1 showed the highest PO2 (group 1: 124.4 +/- 7.7 mmHg; group 2: 46.2 +/- 9.4 mmHg P less than 0.01). Lungs in both group 3 and group 4 showed better lung function and lower wet/dry weight ratio than those in group 2. We conclude that LPD provides better lung preservation by its effects both on pulmonary flush and on storage.

Effect of complement inhibition with soluble complement receptor 1 on pig allotransplant lung function.

BACKGROUND: Lung dysfunction after transplantation continues to be a significant clinical problem. Soluble complement receptor 1 (sCR1) is a potent inhibitor of complement activation. We evaluated the inhibitory effect of sCR1 on complement activation and reperfusion injury in pig lung allografts. METHODS: In a randomized and blinded study, left lung transplantation was performed in 13 pigs. Donor lungs were flushed and then stored for 30 hr at 4 degrees C. Control pigs (n=7) received saline, and the treatment group (n=6) received 15 mg/kg sCR1 1 hr before reperfusion. One hour after reperfusion, the right pulmonary artery was clamped for 10 min to assess the function of the transplanted lung. Pulmonary function was assessed again on day 3. RESULTS: Complement inhibition was 93% in the sCR1 group and returned to baseline (8% inhibition) after 3 days. There was a trend toward a higher partial pressure of oxygen at 1 hr in the sCR1 group compared with the control group (mean +/- SE: 408+/-42 mmHg vs. 288+/-69 mmHg, P = 0.19). Alveolar ventilation was better in the sCR1 group than in the control group (P = 0.01) at 1 hr. Mixed venous saturation was significantly lower in the control group at both 1 hr (P = 0.02) and 3 days (P = 0.001). The wet/dry weight of the lung tissue was lower in the sCR1 group compared with the control group on day 3 (P < 0.05). Chemiluminescence, an index of phagocyte priming, was lower in the sCR1 group when cells were stimulated with complement opsonized zymosan but not when stimulated with zymosan or phorbol myristate acetate. CONCLUSION: sCR1 improves ventilation, reduces pulmonary edema, and may be beneficial in improving posttransplant lung oxygenation.

A method for safe twelve-hour pulmonary preservation.

The clinical application of lung transplantation is severely limited by the shortage of suitable donor organs. Current techniques of lung preservation allow a maximum of 4 to 6 hours of safe ischemic time. The function of canine left lung allografts stored for 12 hours after being cooled by pulmonary artery flush was studied. Two types of flush solution were used: group I; Euro-Collins solution; group II, low-potassium-dextran solution. Lung function was studied immediately and 3 days after transplantation. This protocol enables study of acute preservation-related lung injury and the delayed manifestations of ischemic and reperfusion injury after a 3-day period of recovery. Inflatable cuffs were placed around each pulmonary artery at operation and were attached to subcutaneous injection ports. Temporarily occluding either pulmonary artery allowed independent study of the native or transplanted lung. Using this model, we were able to demonstrate reliable and reproducible preservation of lungs for 12 hours. The low-potassium-dextran solution provided significantly better immediate function of the preserved lung than the Euro-Collins solution: arterial oxygen tension 509 +/- 15 mm Hg versus 111 +/- 16 mm Hg (p less than 0.0001). Function on the third day was excellent for both groups. Pulmonary artery pressure, pulmonary vascular resistance, and carbon dioxide tension were not significantly different between the groups immediately or on day 3.

Adenoid cystic carcinoma of the airway: thirty-two-year experience.

METHODS: We have reviewed our experience in 38 patients with adenoid cystic carcinoma of the upper airway seen between 1963 and 1995. The mean age was 44.8 years (15 to 80 years) with a male/female ratio of 1:1.1. Thirty-two of the 38 patients were treated by resection and reconstruction (primary anastomosis 28; Marlex mesh prosthesis 4). Twenty-six of the 32 patients undergoing resection received adjuvant radiotherapy. Six patients with unresectable tumors were treated primarily with radiotherapy only. RESULTS: Pathologic examination revealed local invasion beyond the wall of the trachea in all patients. In a majority, microscopic extension was found in submucosal and perineural lymphatics, well beyond the grossly visible or palpable limits of the tumor. Lymphatic metastases were relatively uncommon, occurring in only five of 32 (19%) patients undergoing resection. Metachronous hematogenous metastases occurred in 17 of 38 patients (44%). Thirteen of these 38 patients (33%) had pulmonary metastases. Sixteen of 32 resections were complete and potentially curative. There were two deaths within 30 days of operation. The mean survival in the 14 patients undergoing complete resection was 9.8 years (12 months to 29 years). Sixteen of 32 resections were incomplete (residual tumor at the airway margin on final pathologic examination), with one operative death occurring in this group. The mean survival in the 15 surviving patients was 7.5 years (4 months to 21 years). Six patients were treated with primary radiation only and had a mean survival of 6.2 years (2 months to 14.3 years). In the patients with pulmonary metastases, mean survival was 37 months (4 months to 7 years) from the time of diagnosis of the pulmonary metastasis until their death. CONCLUSION: Adenoid cystic carcinoma of the upper airway is a rare tumor, which is locally invasive and frequently amenable to resection. Although late local recurrence after resection is a feature of this tumor (up to 29 years), excellent long-term palliation is commonly achieved after both complete and incomplete resection. There was a small difference in survival between patients having complete and incomplete resection. Long periods of control can be obtained with radiotherapy alone. The best results, in this series of patients, were obtained by resection. Adjuvant radiotherapy is assumed to favorably influence survival.

Rapid reperfusion causes stress failure in ischemic rat lungs.

OBJECTIVE: Rapid reperfusion may be injurious to the ischemic lung. Our aim was to confirm that slow reperfusion improves postischemic pulmonary function and to elucidate the ultrastructural changes associated with slow versus rapid reperfusion. METHODS. We used an ex vivo perfused rat lung transplant model to study the effect of slow versus rapid reperfusion on subsequent lung function and morphologic conditional. Functional assessment was performed in (1) fresh lung, slowly reperfused; (2) fresh lung, rapidly reperfused; (3) ischemic lung (4 hours at 22 degrees C), slowly reperfused; and (4) ischemic lung, rapidly reperfused. RESULTS: In group 4, the shunt fraction (P=.001), airway pressure (P=.001), and wet/dry ratio (P=.01) were significantly higher than in groups 1 through 3. Light and electron microscopy of slowly reperfused ischemic lungs (n=4) appeared normal. Rapidly reperfused ischemic lungs (n=4) demonstrated massive alveolar edema hemorrhage, and epithelial "blebbing" by light microscopy. Electron microscopy identified the blebbing as separation of the epithelial layer from an intact basement membrane by edema fluid. The epithelial layer was disrupted in numerous locations. Complete disruption of all layers of the blood-gas barrier was occasionally present. CONCLUSION: Rapid reperfusion of the ischemic lung is an important contributing factor to reperfusion lung injury resulting in mechanical stress failure of the alveolar/capillary barrier. Gradual reintroduction of blood flow to the ischemic lung improves oxygenation.

The effect of pulmonary arterial flow and positive end-expiratory pressure on retrograde bronchial mucosal blood flow.

Bronchial viability within the first few days after lung transplantation depends on collateral blood flow from the pulmonary to the bronchial circulation. In the present study the relationship between pulmonary arterial flow and retrograde bronchial blood flow, and the effect of positive end-expiratory pressure on bronchial blood flow were evaluated by laser Doppler velocimetry in an isolated in situ lung perfusion model. Nine adult mongrel dogs were exsanguinated by way of a left atrial cannula. Blood was pumped by a roller pump into the main pulmonary artery. Lungs were perfused at random flow (in 0.5 L/min increments) at rates of 1 to 3 L/min. Steady-state laser Doppler velocimetric measurements at each level of flow were made at the tracheal carina and both bronchial carina. Pump flow was then set at baseline cardiac output and positive end-expiratory pressure was applied. Steady-state laser Doppler velocimetric measurements were obtained at each level of positive end-expiratory pressure (5 cm H2O and 10 cm H2O). Bronchial blood flow correlated well with pulmonary arterial flow (for the tracheal carina; rs = 0.912 and p less than 0.0005; for the right bronchial carina, rs = 0.799, p less than 0.0005; for the left bronchial carina, rs = 0.917, p less than 0.0005; where rs is the common correlation coefficient). The bronchial blood flow at the left bronchial carina and the right bronchial carina were significantly higher than at the tracheal carina (p less than 0.005 and p less than 0.05, respectively). At baseline cardiac output, bronchial blood flow in the in situ model was approximately 50% lower than observed in the intact animals. Positive end-expiratory pressure increased the bronchial blood flow at the tracheal carina and both bronchial carina (p less than 0.05).

The role of dextran 40 and potassium in extended hypothermic lung preservation for transplantation.

We have previously demonstrated that a low-potassium dextran solution provides superior and more reliable preservation of lungs for 12 hours than that provided by the commonly used Euro-Collins solution. This study was designed to examine the individual contributions of dextran 40 and a low (extracellular) potassium concentration to lung preservation. In a randomized, blinded study using an in vivo canine single-lung transplant model, lungs preserved with low-potassium dextran solution (K+, 4 mmol/L; dextran 40, 20 gm/L) were compared to lungs preserved with low-potassium, no-dextran solution (K+, 4 mmol/L) and high-potassium dextran solution (K+, 123 mmol/L; dextran 40, 20 gm/L). The lungs were assessed immediately and 3 days after transplantation. The low-potassium dextran solution provided excellent immediate pulmonary function with little variability (arterial oxygen tension, 519 +/- 12 mm Hg, measured on the transplanted lung alone, inspired oxygen fraction = 1.0, n = 6). Removing the dextran 40 from the flush solution (low-potassium group) led to a significant deterioration in pulmonary function (arterial oxygen tension, 243 +/- 78 mm Hg, n = 6, p less than 0.01). The high-potassium dextran solution provided extremely poor preservation (arterial oxygen tension, 176 +/- 79 mm Hg; n = 6; p less than 0.01). Two animals in this group died within 6 hours of operation. Viability of the transplanted bronchus was significantly improved with the two solutions containing dextran 40. These results indicate that dextran 40 and low potassium concentration both contribute significantly to the uniformly excellent 12-hour lung preservation seen with the low-potassium dextran solution.

Improved lung preservation with dextran 40 is not mediated by a superoxide radical scavenging mechanism.

Improved lung preservation with a low-potassium dextran-containing solution has been previously demonstrated. In a subsequent study, it was shown that dextran 40 contributes significantly to this improved preservation. In the current in vitro study, human neutrophils suspended in lung preservation solutions (low potassium with dextran and low potassium without dextran) were stimulated to produce superoxide radicals. The presence of dextran in the solution did not significantly alter the amount of superoxide measured in the assay (low potassium with dextran, 4.149 +/- 0.144 nmol/10(6) cells/20 min; low potassium without dextran, 3.896 +/- 0.215; p greater than 0.2). This suggests that dextran 40 did not appreciably scavenge superoxide radicals, nor did it alter the production of superoxide radicals by stimulated neutrophils. Thus the significantly improved lung preservation seen with the use of dextran 40 is probably not mediated by a superoxide radical scavenging process.

The effect of ischemic time and temperature on lung preservation in a simple ex vivo rabbit model used for functional assessment.

Despite 25 years of research in lung transplantation, little progress has been made in methods for improving lung preservation. To evaluate many factors that may affect lung function after preservation, we have developed a simple, reliable, and inexpensive animal model. This consists of an isolated rabbit lung preparation perfused with blood and ventilated with a closed-circuit system. Heart-lung blocks were harvested and the left lung was assessed after ligation of the right pulmonary artery and right main-stem bronchus. On completion of a storage period, the left lung was ventilated and perfused with fresh rabbit venous blood at a rate of 40 ml/min for 10 minutes. Assessment of lung function included gas analysis of infused and effluent blood, oxygen uptake, mean pulmonary artery perfusion pressure, and mean airway pressure. A control group and six preservation groups were evaluated, each with different storage temperatures (38 degrees C, 34 degrees C, 23 degrees C, 15 degrees C, 10 degrees C, and 4 degrees C). For each temperature, ischemic periods ranging from 1 to 30 hours were studied. In the control group, the lungs were assessed immediately after being harvested. In the preservation groups, the lungs were kept partially inflated, stored at a predetermined temperature by immersion, and later assessed after variable ischemic periods. Our studies demonstrated the following: (1) The degree of impaired lung function produced by ischemia is reflected by a decrease in oxygen uptake and in oxygen tension of the effluent pulmonary venous blood and an increase in pulmonary artery perfusion pressure; (2) hypothermia improves ischemic tolerance; (3) preservation of lung at 10 degrees C is superior to preservation at 15 degrees C and 4 degrees C. This screening model has allowed evaluation of independent multiple factors and methods pertinent to lung preservation and enables one to assess lung function reliably and rapidly.

Radiologic correlation with early physiologic function of the transplanted canine lung.

There is no single reliable method for assessment of the transplanted lung. Multiple modes of assessment are therefore used. In a canine model designed to assess lung preservation, the reliability of information gained from chest radiographs performed in the early post-transplant period was examined. The function of 20 left lung allografts, stored for 12 hours after pulmonary artery flush preservation was studied. Radiographs graded according to disease severity were compared with physiologic function of the transplanted lung assessed immediately and at three days post-transplantation. This protocol enables study of acute preservation-related lung injury and the delayed manifestations of ischemic and reperfusion injury after a three day period of recovery, while avoiding confounding rejection and infectious episodes. The chest radiograph did not reliably reflect function of the flush-preserved transplanted lung. Thus, relying only on this modality may lead to erroneous conclusions. In this study, the progression of radiographic changes associated with the "reimplantation response" differed from previous descriptions, possibly reflecting differences in operative technique or improved lung preservation.

Nutritional assessment of the lung transplant patient: body mass index as a predictor of 90-day mortality following transplantation.

BACKGROUND: It is well documented that malnourished and/or obese surgical patients have increased morbidity and mortality post-operatively. Only a few studies investigating the effect of nutritional status on mortality are available pertaining to the transplant population. Since limited data are available on the nutritional status and its effects on mortality in the lung transplant population, we sought to ascertain whether there is an association between mortality and preoperative nutritional status. METHODS: We examined mortality during the first 3 months after transplantation. Patients were grouped by body mass index (BMI) categories as < 17 kg/m(2), 17 to < 20 kg/m(2), 20 to 25 kg/m(2) (reference group), > 25 to 27 kg/m(2), and > 27 kg/m(2). Additional risk factors retrieved from the pre-transplant records included age, gender, diagnosis, energy requirements, protein requirements, protein and caloric intake, and weight history. Logistic regression for univariate and multivariate analysis for mortality used recipient age, gender, disease category, pre-transplant cytomegalovirus (CMV) serology, transplant type (single or bilateral), and donor age, gender, and CMV serology. RESULTS: The likelihood estimates or odds ratios (ORs) of the risk of death within 90 days of lung transplantation for the BMI categories compared to the reference group were 3.7 for BMI < 17 kg/m(2) (p = 0.085), 1.6 for BMI < 17 to 20 kg/m(2) (p = 0.455), 3.5 for BMI > 25 to 27 kg/m(2) (p = 0.069), and 5.0 for BMI > 27 kg/m(2) (p = 0.003). CONCLUSIONS: In patients with a pre-transplant BMI < 17 kg/m(2) or > 25 kg/m(2) the risk of dying within 90 days post-transplant was increased. In patients with a pre-transplant BMI of > 27 kg/m(2) the risk was significantly higher in than the reference group.

Effect of hypotension preceding death on the function of lungs from donors with nonbeating hearts.

BACKGROUND: A shortage of suitable brain-dead donors continues to severely limit lung transplantation. Use of donors with nonbeating hearts has been suggested as a solution. Lungs are unique, in that aerobic metabolism can continue in the absence of blood circulation because oxygen is present in airways and alveoli. Animal studies have shown reasonable cadaveric graft function up to several hours after sudden death by drug administration. However, hemodynamic instability before death may worsen lung function through activation and pulmonary sequestration of neutrophils and release of inflammatory mediators. Because many potential cadaveric donors experience hypotension before death, this study was undertaken to assess the effect of hypotensive shock on cadaveric lung viability. METHODS: A rat isolated lung reperfusion model was used to assess pulmonary function over 3 hours of reperfusion or until gross pulmonary edema developed. Twenty-five rats were randomly allocated to the following study groups, which were based on status before lung harvest: (1) control: no interventions; (2) hypotensive: 1 hour of hypotension by exsanguination to a mean blood pressure of 30 to 40 mm Hg; (3) cadaver: death by cervical dislocation followed by 3 hours of in situ lung ischemia; (4) hypotensive + 3 hours cadaver: 1 hour of hemorrhagic shock, followed by death and 3 hours of in situ ischemia; (5) hypotensive + 2 hours cadaver: similar to group 4, except the in situ ischemia was abbreviated to 2 hours. RESULTS: No significant differences were found among group 1, 2, or 3 lungs with regard to wet to dry weight ratios, gas exchange, and pulmonary arterial or airway pressures. However, all group 4 lungs became grossly hemorrhagic and developed severe pulmonary edema within 10 minutes of reperfusion. Group 5 lungs fared only marginally better, with two of five lungs tolerating 3 hours of reperfusion. CONCLUSIONS: A period of hypotension before death severely impairs cadaveric lung viability.

Transplant immunosuppression increases and prolongs transgene expression following adenoviral-mediated transfection of rat lungs.

BACKGROUND: Gene therapy provides the potential to modify donor organs to better withstand transplantation, but this has yet to be realized. In vivo gene transfer using adenoviral vectors has had limited success because of host immune response that induces inflammation and limits the amount and duration of transgene expression. We hypothesize that transplantation immunosuppression can attenuate the post-transfection host-immune response to allow for improved gene transfer following adenoviral-mediated transfection. METHODS: We intratracheally transfected with adenovirus containing the beta-galactosidase gene and randomized the rats to either the immunosuppression group, receiving daily cyclosporine, azathioprine, and methylprednisolone, or the control group, receiving no immunosuppression. We evaluated transgene expression and post-transfection inflammation at time points ranging from 1 day to 5 weeks. RESULTS: Following transfection, control rats showed relatively low levels of transgene expression, which rapidly decreased to non-detectable levels. In contrast, immunosuppressed rats demonstrated significantly higher levels of transgene expression overall (p < 0.00005), peaking at almost 3 times that of the control group (p < 0.02), and showing prolonged and elevated transgene expression at 5 weeks (p < 0.02). On histologic sections of the lungs, immunosuppressed rats exhibited overall lesser grades of post-transfection inflammation. CONCLUSIONS: Transplant immunosuppression provides the means to attenuate the severe immune response to adenoviral-mediated gene transfection and thereby increase and prolong transgene expression.

Use of a hypoxic lung as a deoxygenator to provide extended assessment of pulmonary function in rats.

Isolated perfused lung systems are commonly used to assess lung function in experimental studies. Assessment of hemodynamics and gas-exchange function in these systems is limited by the availability of venous blood. This study describes and validates a rat lung perfusion circuit in which a double-lung block ventilated with a hypoxic gas mixture [inspired O2 fraction (FIO2) 0.04; inspired CO2 fraction 0.08; deoxygenator (Deoxy) block] is used to provide blood with blood gases that are similar to mixed venous values to perfuse a study lung (FIO2 0.21; left lung only). This allows extended assessment of hemodynamics and gas exchange. Fifty adult male Wistar rats (300-400 g) were used as double-lung donors. Twenty-five perfusions (of both Deoxy and study lungs) were performed in four protocols (groups 1-5; n = 5). In protocol 1 (group 1), we tested whether exposure to room air affects the gas composition of the blood in the system. We found that the gas composition of the venous reservoir blood was identical to that of the blood entering the study block. In protocol 2, the effect of perfusion time and perfusion flow rate on the stability of the system was assessed. Lungs were perfused at 4 and 12 ml/min (groups 2 and 3, respectively), and the procedure was discontinued if edema or a marked decline in hemodynamics or gas-exchange function was observed. Pulmonary function was excellent and remained stable for 3 (at 12 ml/min) and 5 h (at 4 ml/min). In protocol 3, we examined whether hypoxic ventilation in the Deoxy lungs affects the stability of the system. Despite the low FIO2 used in the Deoxy lungs, the mean pulmonary arterial pressure-to-blood flow relationships in the study and Deoxy lungs were similar. Finally, in protocol 4, perfusion of a damaged study lung did not impair the function of the system. We conclude that this model permits reliable assessment of pulmonary function in rats under controlled ventilation and perfusion conditions. The use of a Deoxy double-lung block simplifies the perfusion apparatus and eliminates the main cause of instability of other systems that use an anesthetized host animal to provide venous blood.

Simultaneous single-lung transplantation and lung volume reduction.

We report our experience with 2 cases of simultaneous single-lung transplantation and lung volume reduction for emphysema. The lung volume reduction was undertaken electively in an attempt to improve overall lung function above that to be expected from single-lung transplantation alone. There were no postoperative problems related to the addition of lung volume reduction. The pulmonary function at 3 months was greater than that seen in a retrospective group of bilateral lung transplants previously reported from our institution.

Pulmonary arteriography for the assessment of technical feasibility of sleeve resection in lung cancer.

BACKGROUND: Pulmonary arteriography has been reported to be useful in the preoperative assessment of patients with lung cancer to determine the technical resectability and feasibility of pneumonectomy by imaging the main right and left pulmonary arteries. In this report, we describe the use of selective pulmonary arteriography in the assessment of lobar resectability. METHODS: Selective pulmonary arteriography provides a detailed anatomic view of the lobar branches and has been used at our institution for the past 30 years to preoperatively investigate patients who are candidates for a sleeve lobectomy. RESULTS: Three cases are described that demonstrate the usefulness of selective pulmonary arteriography in the assessment of the technical feasibility of sleeve resection in patients with lung cancer. CONCLUSIONS: Arteriographic findings may accurately show whether a sleeve lobectomy is technically possible, that only a pneumonectomy is possible, or that the only safe way to ensure clearance of the pulmonary artery is to perform arterioplasty. This information may obviate an unnecessary thoracotomy in patients who are judged on the basis of a physiologic assessment to be unable to tolerate a pneumonectomy.

Role of basic fibroblast growth factor in revascularization of rabbit tracheal autografts.

Despite omentopexy of the bronchial anastomosis, donor airway ischemia remains a problem after lung transplantation. This study examined the hypothesis that surface abrasion and topical application of basic fibroblast growth factor (bFGF) would enhance omental revascularization of trachea in a rabbit heterotopic autograft model. Tracheal segments were excised, primary tracheal anastomoses performed, and the segments placed in the peritoneal cavity wrapped in omentum. Animals were randomized to one of six groups according to tracheal segment treatment: control, surgical abrasion, Surgicel wrap with topical bFGF, Surgicel wrap with bFGF vehicle, Gelfoam wrap with bFGF, and topical bFGF alone. One week later, animals were heparinized, perfused with Aquablak dye, and killed. Tracheal segments were excised and sectioned for light microscopic quantitative assessment of viability and dye perfusion. There was no significant improvement in viability or perfusion between abraded tracheal segments or segments treated with bFGF/Gelfoam or bFGF alone when compared with control segments. Airways wrapped in Surgicel had significantly greater ischemic injury compared with the control group, regardless of bFGF application. Neither surgical abrasion nor topical bFGF increased omental revascularization of transplanted tracheal segments after 7 days.

Neuropathology of chronic pancreatitis in humans.

To investigate the pathogenesis of pain in chronic pancreatitis, tissue resected from 50 patients with this condition was examined by light microscopy. An examiner, blinded to clinical and pathological data, graded perineural fibrosis, inflammation and the composition of inflammatory infiltrate in 2132 separate perineural fields. Correlation of perineural fibrosis and inflammation grading with alcohol ingestion and pain severity was insignificant. Pain severity did correlate with the timing of alcohol consumption. Although calcification significantly affected pain severity, the status of duct dilatation was not significant. Eosinophils were observed in disproportionate numbers in the perineural infiltrate. The correlation of percentage eosinophilic infiltrate and pain severity was highly significant. Timing of alcohol consumption also correlated significantly with the percentage eosinophilic infiltration. As eosinophils are known to be cytotoxic and injurious to tissue by liberation of enzymes through degranulation, the findings of this study suggest that the pain of chronic pancreatitis may be mediated by perineural eosinophils, through a chemotactic mechanism involving alcohol.