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Biomedical subjects

G A Patterson

Publications and source records attributed to G A Patterson.

At least 199 records · Page 11Linked to original sources
PubMed1992

[Revascularization of heterotopic isotransplants of the rat trachea using an omentum flap].

Donor airway ischemia remains a significant problem following lung transplantation. An acceleration of local bronchial revascularization would be advantageous for bronchial healing. In the present study, the quantitative effects of omentopexy on tracheal revascularization and epithelial regeneration were investigated in a heterotopic rat tracheal isograft model. Tracheal segments were harvested from donor rats and heterotopically implanted into the omentum of syngeneic recipient rats. Tracheal segments were wrapped for 2 days (group 2), 7 days (group 3) or 14 days (group 4). Tracheal segments in group 1 were harvested and not re-implanted. Following sacrifice of the animals after 2, 7 or 14 days, the vascularity of the tracheas and the tracheal epithelial morphology were assessed histologically using morphometric image analysis. The vascularity of tracheal segments was significantly higher in group 1 (native tracheas) compared to all other groups. Vascularity in group 4 segments (omental wrap for 14 days) was significantly greater than in group 3 segments (omental wrap for 7 days). Tracheal epithelial morphology was characterized by non-confluent single epithelial cells at day 2, a confluent multilayered nonciliated epithelium after 7 days of omental wrap and a morphologically normal epithelium after 14 days of omental wrap. Our new heterotopic rat tracheal isograft model allows histologic assessment and quantification of local revascularization and epithelial regeneration of tracheal segments by omentopexy.

Anastomosis, Surgical↗
PubMed1992

Retransplantation following isolated lung transplantation.

The results of retransplantation for early allograft failure are discouraging. Fortunately, with recent technical advances and improved postoperative immunosuppression, airway complications have been significantly reduced. It is now unusual to see patients with airway complications following lung transplantation. This group of patients is not likely to represent a large population in need of retransplantation in the future. However, rejection-mediated OB remains a persistent problem seen in all transplant centers. The group of patients who deteriorate despite augmented immunosuppression will put increasing pressure on transplant programs to provide the only known solution for survival: retransplantation. In the Toronto experience, only 1 patient survived early retransplantation. Three of the 5 recipients retransplanted late in their course have survived and 2 are presently alive and well. Yet this is in sharp contrast to the current 80% 1-year survival for initial transplant recipients. As the demand for donor lungs increases with the growing need for first-time procedures, the use of donor lungs for retransplantation becomes a significant problem. The decision whether to allocate a donor lung (and commit significant hospital resources) to a retransplant recipient or to a first-time recipient is difficult. A patient with early graft failure has a dismal prognosis and a decision not to retransplant may be straightforward. However, the decision to retransplant a patient who has developed OB late following their initial transplant is much more difficult. It is still our responsibility to manage this limited resource and provide donor lungs to those who have the optimal chance of survival.

Adolescent↗
PubMed1992

Staging: the key to rational management of lung cancer.

Staging is the quantitative assessment of malignant disease and allows logical groupings of patients with a similar extent of disease for prognostic, therapeutic, and analytic purposes. In bronchogenic carcinoma a stage is assigned based on size, location, and the extent of invasion of the primary tumor, as well as the presence of any regional or metastatic disease. Selecting the most appropriate treatment for a patient with bronchogenic carcinoma depends on precise staging. The extent of local invasion and presence of metastatic disease will determine the likelihood of complete resection and possible cure. Careful assessment of the history, blood chemistry, radiographic studies, bronchoscopy, mediastinoscopy, and exploration (thoracotomy) are all important staging tools. Routine radionuclide scans have no useful role when there is no clinical or laboratory evidence of metastases. The T status of a tumor is best judged by bronchoscopy and at thoracotomy. Thoracic surgeons must be familiar with the techniques available to determine T status intraoperatively and use this information when planning resection. Computed tomography of the chest has fallen short in predicting direct invasion of the mediastinum and chest wall. Cervical and anterior mediastinoscopy remain important tools in determining operability. Intraoperative assessment of node involvement determines the extent of resection and likelihood of cure.

Humans↗
PubMed1992

Bilateral lung transplantation for cystic fibrosis. The Toronto Lung Transplant Group.

Between March 1988 and March 1991, 17 patients underwent bilateral lung transplantation for end-stage lung disease caused by cystic fibrosis. There were 11 male and six female patients. Ages ranged from 19 to 41 years (mean age 28 years). Preoperative mean arterial oxygen tension with the patient breathing room air was 54 +/- 6 mm Hg; forced vital capacity, 1.8 +/- 0.7 L; forced expiratory volume in 1 second, 0.9 +/- 0.3 L; and 6-minute walk test, 506 +/- 44 m. Immunosuppression consisted of cyclosporine, azathioprine, and prednisone. Induction immunosuppression was obtained with Minnesota antilymphocyte globulin. All patients received perioperative antibiotics according to sputum cultures and sensitivities. There were six operative deaths, four of which resulted from bacterial infection. Two patients required a second transplantation, one receiving a single lung and one undergoing bilateral lung replacement. Significant functional improvement was observed in all survivors. At 3 months follow-up, mean arterial oxygen tension on room air was 95 +/- 6 mm Hg (p less than 0.01); forced vital capacity, 3 +/- 0.8 L (p less than 0.01); forced expiratory volume in 1 second, 2.6 +/- 0.9 L (p less than 0.01); and 6-minute walk test, 678 +/- 47 m (p less than 0.01). The actuarial survival rate was 66% at 3 months and 58% at 6, 12, and 24 months. The most frequent cause of morbidity and mortality was acute pneumonia resulting from Pseudomonas cepacia. For patients with respiratory failure caused by cystic fibrosis, bilateral lung transplantation is an effective treatment option associated with significant functional improvement.

Adult↗
PubMed1992

Pulmonary transplantation. Early and late results. The Toronto Lung Transplant Group.

Between November 1983 and March 1991, we performed 50 single and 40 double lung transplants in 82 recipients. Early deaths occurred in six (13%) single and in eight (21%) double lung transplant recipients. Late deaths occurred in 11 (28%) single and in one (3%) double lung recipients. Twenty-three of 37 (62%) single and 17 of 24 (71%) double lung transplant recipients have survived at least 1 year after the operation. In patients surviving at least 3 months after the operation (36 of 47 single lung transplant [77%] and 28 of 37 double lung transplant recipients [76%]), significant improvement occurred in arterial blood gases, pulmonary function tests, and exercise capacity. During our initial experience, airway anastomotic complications were the main cause of early morbidity and mortality. With newer surgical techniques and improved perioperative care, airway complications are now uncommon. Infectious complications, either bacterial (Pseudomonas cepacia) or viral (cytomegalovirus), are now the main cause of early mortality. Chronic rejection in the form of obliterative bronchiolitis has become a frequent cause of late morbidity.

Adult↗
PubMed1991

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.

Airway Obstruction↗
PubMed1991

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.

Alkaline Phosphatase↗
PubMed1991

The effect of PGE1 and temperature on lung function following preservation.

We studied the effect of a vasodilator (prostaglandin E1) as well as flush (F) and storage (S) temperatures (4 degrees C or 10 degrees C) on lung preservation in an isolated rabbit lung perfusion model. Low-potassium dextran (LPD) or Euro-Collins (E-C) solution was used as flush solution. Six groups of six animals were studied: group 1 (LPD, 4 degrees C F-S), group 2 (LPD with PGE1, 4 degrees C F-S), group 3 (E-C with PGE1, 4 degrees C F-S), group 4 (LPD, 10 degrees C F-S), group 5 (LPD with PGE1, 10 degrees C F-S), group 6 (E-C with PGE1, 10 degrees C F-S). After 18-hr preservation, left lungs alone were ventilated, and reperfused with fresh venous blood. PaO2, PaCO2, pulmonary artery pressure (PAP), tracheal pressure (Pt) during reperfusion, and wet/dry weight (W/D) ratios were measured. PaO2 after LPD with or without PGE1 was significantly higher than after E-C with PGE1 at 4 degrees C (95.8 +/- 11.5 mmHg in group 1 or 102.7 +/- 8.6 in group 2 vs. 41.8 +/- 10.5 in group 3, P less than 0.01) and at 10 degrees C (119.3 +/- 2.3 in group 4 or 131.1 +/- 6.2 in group 5 vs. 54.6 +/- 5.2 in group 6, P less than 0.01). PaCO2, PAP, Pt, and W/D ratios in the LPD groups were lower than in the E-C groups. LPD/PGE1 and LPD alone produced similar pulmonary preservation. PaO2 of lungs flushed with LPD and preserved at 10 degrees C was higher than that of lungs stored at 4 degrees C. We conclude that LPD solution is superior to E-C solution in this ex vivo rabbit lung preservation model, even when PGE1 is used. A moderate dose of PGE1 did not improve the performance of LPD as a flush solution. Pulmonary preservation with LPD at 10 degrees C is superior to preservation at 4 degrees C.

Alprostadil↗
PubMed1991

Low-potassium UW solution for lung preservation. Comparison with regular UW, LPD, and Euro-Collins solutions.

University of Wisconsin solution has been used successfully in clinical kidney and liver preservation. The object of this study was to determine if low-potassium UW (LPUW) solution could be applied to pulmonary preservation. Rabbit lungs were stored after hypothermic pulmonary artery (PA) flush with four different solutions (group 1: low-potassium dextran (LPD) solution, group 2: high-potassium UW (HPUW) solution, group 3: LPUW solution, group 4: modified Euro-Collins (E-C) solution). The lungs were preserved at 10 degrees C for 30 hr and evaluated in an ex vivo ventilation/perfusion apparatus using fresh pooled venous rabbit blood. Mean PA flush pressures (MFP) during harvesting were significantly lower in groups 1 and 3 (8.1 +/- 1.0 mmHg and 7.3 +/- 0.6 mmHg, respectively; mean +/- SEM) than in groups 2 and 4 (15.5 +/- 1.7 mmHg and 12.3 +/- 0.9 mmHg, respectively). Lungs in groups 1 and 3 showed significantly higher PaO2 (103.5 +/- 8.0 mmHg and 89.3 +/- 7.2 mmHg) than groups 2 and 4 (48.3 +/- 7.7 mmHg, 66.7 +/- 4.7 mmHg). Groups 1 and 3 showed significantly lower wet/dry weight (W/D) ratios after reperfusion (6.21 +/- 0.15 and 6.39 +/- 0.23) than groups 2 and 4 (7.70 +/- 0.57 and 7.13 +/- 0.21, respectively). There were no significant differences in MFP, PaO2, PaCO2, mean pulmonary artery pressure, or W/D ratio between groups 1 and 3. These results suggest that LPUW solution may be as beneficial as LPD solution for pulmonary arterial flush and lung preservation.

Adenosine↗
PubMed1991

Use of an isolated in situ canine lung perfusion model to evaluate dopamine clearance by the lung.

An isolated in situ lung perfusion model was used to assess dopamine clearance by the lungs in 12 dogs. The preparation consisted of a closed perfusion system in situ, in which systemic arterial blood supply was interrupted. Blood flow to the lungs was maintained at presurgery flow rates. The inflow was restricted to the lungs by the pulmonary arteries and outflow was limited to the pulmonary veins. Pulmonary artery pressure, temperature and pO2 were maintained at physiological levels. After confirmation of a stable base line, one of 3 doses (1, 2, or 5 micrograms/kg/min) of dopamine was infused over 30 min to achieve steady-state blood concentrations, then blood samples were drawn at specified times during and after the infusion. Dopamine plasma concentrations were analyzed by high performance liquid chromatography with electrochemical detection. Dose-dependent disposition of dopamine was observed in both plasma concentration-time profiles and in clearance (20.3 +/- 9.6 ml/min/kg at 5 micrograms/kg/min vs. 41.6 +/- 19.1 ml/min/kg at 1 micrograms/kg/min, P = 0.038). A sham experiment revealed that the blood in this experimental preparation contributed less than 10% to the total clearance of dopamine. This study revealed that our isolated in situ model is an excellent method to evaluate the role of the lungs in drug removal. Furthermore, it confirmed that the lungs contribute to the clearance of dopamine from the body.

Animals↗
PubMed1991

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).

Animals↗