Biomedical subjects

G A Patterson

Publications and source records attributed to G A Patterson.

At least 109 records · Page 6Linked to original sources

PubMed1996

Attenuation of rat lung isograft reperfusion injury with a combination of anti-ICAM-1 and anti-beta2 integrin monoclonal antibodies.

Four different combinations of monoclonal antibodies against rat ICAM-1, CD-11a, and CD-18 were utilized to determine the relative importance of LFA-1, Mac-1, and ICAM-1 in a rat model of severe lung allograft reperfusion injury. Negative control animals were given phosphate buffered saline (the carrier solution for the antibodies), while positive control animals were rendered neutropenic by the administration of a polyclonal mouse IgG. Antibodies were given with the donor lung flush, prior to left lung graft reperfusion, or both. Isolated graft function was determined 24 hr after implantation by arterial blood gas (ABG), and after sacrifice the native and transplanted lungs underwent bronchoalveolar lavage for alveolar protein quantitation, cell count and differential, and myeloperoxidase assay. Additionally, whole lung homogenates were assayed for myeloperoxidase activity. We found that the combination of anti-ICAM-1 (1 mg/kg) added to the donor lung flush, and anti-CD11a, anti-CD18, and anti-ICAM-1 (2 mg/kg i.v. of each) given to the recipient prior to reperfusion, resulted in significantly improved lung graft pAO2 by ABG, and decreased alveolar protein, cell count, and myeloperoxidase activity compared with control animals. Improvement was less than that seen in the neutropenic recipients, however. We conclude that LFA-1, Mac-1, and ICAM-1 are all important adhesion molecules in lung allograft reperfusion injury--yet even with antibody blockade of all three there are additional mechanisms allowing for neutrophil influx into the lungs.

Animals↗

PubMed1996

Allelotype analysis of esophageal adenocarcinomas: evidence for the involvement of sequences on the long arm of chromosome 4.

The incidence of esophageal adenocarcinoma has increased dramatically over the past 20 years. The causes for this change in incidence and the genetic defects that underlie tumorigenesis are unknown. We performed loss of heterozygosity (LOH) studies in esophageal adenocarcinomas in an effort to map the location of tumor suppressor genes involved in the initiation or progression of this cancer. A genome-wide search for LOH was undertaken using microsatellite repeat polymorphisms and a panel of 27 tumor and matched normal DNAs. This is the first report of an allelotype analysis of esophageal adenocarcinomas. We observed frequent loss of sequences on the short arm of chromosome 17 in the region of the TP53 gene. We also identified a region on 4q lost in more than half of the tumors investigated. The high rate of LOH for 4q sequences speaks to the involvement of an as yet unidentified tumor suppressor gene in esophageal adenocarcinoma tumorigenesis.

Adenocarcinoma↗

PubMed1996

The role of vascular injury and hemodynamics in rat pulmonary artery remodeling.

Vascular remodeling in adult human elastic pulmonary arteries is characterized by diffuse neointimal lesions containing smooth muscle cells expressing extracellular matrix genes. Recent studies suggest vascular injury is needed to initiate remodeling and that growth factor mediators participate in the repair response. However, because neointimal formation is only observed in patients with pulmonary artery blood pressures approaching systemic levels, it has been hypothesized that systemic-like hemodynamic conditions are also necessary. To test that hypothesis, subclavian-pulmonary artery anastomoses were created in Sprague-Dawley rats under three different experimental conditions: no accompanying injury, or after monocrotaline or balloon endarterectomy injury. Pulmonary vascular remodeling was not induced by the subclavian-pulmonary artery anastomosis alone. A non-neointimal pattern of remodeling after mild monocrotaline-induced injury was converted into a neointimal pattern in the presence of the anastomosis. Neointima was also observed after severe, balloon endarterectomy-induced injury even in the absence of anastomosis. Tropoelastin, type I procollagen and TGF-beta gene expression, and angiotensin converting enzyme immunoreactivity, was confined to the neointima resembling the pattern of gene expression and immunoreactivity in human hypertensive elastic pulmonary artery neointimal lesions. These observations introduce the concepts that the type of injury and the associated hemodynamic conditions can modify the elastic pulmonary artery response to injury.

Adult↗

PubMed1996

Experiences of women in cardiothoracic surgery. A gender comparison.

OBJECTIVE: To assess the career and practice experiences of cardiothoracic surgeons, with references to gender similarities and differences. DESIGN: Four-step mailed 115-question survey. SUBJECTS: All identified women, and a cohort of men, certified by the American Board of Thoracic Surgery. MAIN OUTCOME MEASURES: Academic rank, career background, salary, perceptions and experiences of harassment or discrimination, and personal life characteristics. RESULTS: No differences were found in training backgrounds. More men (64%) than women (52%) were in university practices. Comparable proportions of men and women were assistant professors (27%), but more men (27%) than women (13.6%) were full professors. Fifty-eight percent of women and 21% of men reported salaries of less than $250000; 62% of men and 32% of women had incomes over $350000. Career satisfaction was comparable between genders; however, women perceived the promotion process as unfair and unrelated to academic rank. Both genders encouraged men toward a surgical career; men were less likely than women to encourage women to pursue a surgical career (P < .01). Women, much more than men, believed that discrimination hindered their career development (P < .001). Characteristics of personal life were also considerably different between the genders. CONCLUSION: Although practice and training parameters for male and female cardiothoracic surgeons are comparable, work experiences, personal life, and career rewards such as salary and promotion, and perception of discrimination are different.

Academic Medical Centers↗

PubMed1996

Lidocaine reduces reperfusion injury and neutrophil migration in canine lung allografts.

BACKGROUND: Depletion of neutrophils (PMNs) and inhibition of PMN endothelial adhesion ameliorate post-ischemic lung reperfusion injury. Lidocaine reduces PMN adhesion to endothelial surfaces in vivo, and inhibits upregulation of PMN-CD11b/CD18 (Mac-1) in vitro. We evaluated the effect of lidocaine on reperfusion injury, PMN adhesion, and PMN migration in preserved lung allografts. METHODS: Donor lungs were flushed with modified Euro-Collins solution (4 degrees C) after prostaglandin E1 administration (250 micrograms), inflated with 550 mL (inspired oxygen fraction = 1.0), and stored for 24 hours at 1 degree C. Left lung allotransplantation was performed in 13 mongrel dogs. Immediately after reperfusion the recipient right pulmonary artery and bronchus were ligated to permit assessment of allograft function during a 6-hour postreperfusion period. Allograft gas exchange (every 15 minutes) and hemodynamics (every 60 minutes) were assessed. Peripheral blood PMN CD11b expression was determined by flow cytometry. After sacrifice allograft bronchoalveolar lavage fluid PMN count and allograft tissue myeloperoxidase activity were measured. Two groups were studied: In group I (n = 8) lidocaine hydrochloride was added to the donor flush (20 mg/L) solution. In addition lidocaine was given to the recipient at the time of thoracotomy (intravenous bolus of 4 mg/kg) followed by a continuous infusion of 4 mg/kg/h during implantation and the assessment period. Three dogs that did not reach effective lidocaine blood levels at the time of reperfusion (3 to 4 micrograms/mL) were excluded from analysis. Group II animals (n = 5) received no lidocaine. RESULTS: Gas exchange in group I was superior throughout the assessment period (p < 0.05). Bronchoalveolar lavage fluid PMN count in group I was reduced (0.36 x 10(6)PMN/mL versus 6.2 x 10(6) PML/mL; p < 0.03). Group I allograft myeloperoxidase activity was 0.17 U/mg/min compared with 0.28 U/mg/min in group II (p < 0.01). In lidocaine-treated animals PMN CD11b expression was maintained at basal levels 2 hours after reperfusion, compared with group II, in which upregulation of CD11b was observed. Lower lobe wet/dry ratio was not different in the two groups. CONCLUSIONS: Our observations indicate that lidocaine reduces reperfusion injury and inhibits PMN adhesion and subsequent migration to the lung allograft.

Animals↗

PubMed1996

Pentoxifylline in flush solution improves early lung allograft function.

BACKGROUND: Postischemic ischemia reperfusion injury is a frequent and unpredictable problem in clinical lung transplantation. Pentoxifylline (PTX) has a number of effects that could decrease reperfusion injury: reduced neutrophil adhesion to endothelium, decreased production of tumor necrosis factor, decreased platelet aggregation, and increased production of vasodilatory prostaglandins by vascular endothelium. We have demonstrated previously that PTX administered before storage and again during reperfusion reduced lung reperfusion injury. The purpose of the present study was to determine whether these observations were storage or reperfusion effects. METHODS: Fourteen canine left lung allotransplantations were performed. Donor lungs were flushed with modified Euro-Collins solution and stored for 24 hours at 1 degree C. Immediately after transplantation, the contralateral right main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamic indices and arterial blood gas analysis (inspired oxygen fraction 1.0) were assessed for 6 hours before sacrifice. Allograft myeloperoxidase activity was assessed. Bronchoalveolar lavage fluid was obtained from the allograft middle lobe for neutrophil counts. The animals were divided into three groups based on the timing of PTX administration. Group 1 (n = 5) animals received no PTX. Group 2 (n = 4) animals received PTX (20 mg/kg) just before reperfusion as well as continuous infusion (0.1 mg x kg-1 x min-1) during the assessment period. In group 3 (n = 5), donor lungs received PTX (200mg/L) in the flush solution only. RESULTS: Superior gas exchange was noted in the lungs receiving PTX only in the flush solution (group 3). Myeloperoxidase activity in group-3 allografts was significantly reduced. In addition, protein levels and neutrophil counts in the bronchoalveolar lavage fluid were significantly reduced in group-3 allografts. CONCLUSIONS: Pentoxifylline ameliorates lung allograft reperfusion injury when administered in the flush solution. Our data suggest that PTX will prevent graft endothelial dysfunction during 24-hour cold ischemic storage and consequently will prevent neutrophil activation and migration into lung tissue.

Analysis of Variance↗

PubMed1996

Nitroprusside ameliorates lung allograft reperfusion injury.

BACKGROUND: Nitric oxide is believed to play a critical role in the maintenance of vascular integrity through its interaction with neutrophils, platelets, and cellular components of the vessel wall. It has been reported that endogenous nitric oxide level was depressed after ischemia, reperfusion, or both. Furthermore, exogenous as well as endogenous nitric oxide decreases reperfusion-induced vascular dysfunction. We hypothesized that nitroprusside, a potent nitric oxide donor, might enhance lung preservation and reduce posttransplantation lung allograft dysfunction. 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 right main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamics and arterial blood gas analysis (inspired oxygen fraction, 1.0) were assessed for 6 hours before sacrifice. Allograft myeloperoxidase activity and wet-to-dry weight ratio were assessed. Group 1 (n = 5) animals received no nitroprusside. In group 2 (n = 5), the donor lung received nitroprusside in the flush solution (10 mg/L) and recipient animals received 0.2 mg/kg just before reperfusion as well as a continuous infusion (0.11 +/- 0.01 mg.kg-1. h-1) during the assessment period. RESULTS: Superior gas exchange and hemodynamics were noted in lungs receiving nitroprusside. Although allograft myeloperoxidase activity and the total amount of fluid suctioned from the allograft were significantly reduced in group 2, protein levels in bronchoalveolar lavage fluid were not statistically different. CONCLUSIONS: Nitroprusside administration in the flush solution and during reperfusion improves lung allograft function and blood flow, and reduces pulmonary vascular resistance and myeloperoxidase activity in the transplanted lung. Nitroprusside reduces lung allograft reperfusion injury.

Animals↗

PubMed1996

Major histocompatibility complex expression and lung ischemia-reperfusion in rats.

BACKGROUND: Clinical studies in kidney and liver transplantation have suggested that poor early function is associated with increased graft loss due to rejection. Ischemia-reperfusion injury may contribute to rejection by enhancing graft immunogenicity. METHODS: A rat model of unilateral in situ pulmonary ischemia-reperfusion was used to examine class II major histocompatibility complex (MHC) antigen expression. The effects of deflation during ischemia (which augments subsequent injury) as well as concurrent allostimulation were also examined. Major histocompatibility complex expression was examined 9 days after ischemia using the binding of radiolabeled anti-class II antibody and immunohistochemistry. RESULTS: Four hours of ischemia in full inflation or 2 hours of atelectatic ischemia both led to severe lung injury. Ischemia-reperfusion injury led to greater MHC expression in the ischemic lung compared with the nonischemic side. Allostimulation with mononuclear cells did not increase MHC expression in the nonischemic lung but did enhance the increase found in the ischemic lung. This was not due to a graft-versus-host response because allostimulation with F1 cells also led to a significant increase. CONCLUSIONS: Severe ischemic lung injury leads to significant increases in MHC expression, detectable after 9 days of reperfusion. Deflation during ischemia, which augments lung injury, also augments increased MHC expression. Concurrent allostimulation with foreign mononuclear cells appears to potentiate increased MHC expression after ischemia. Increases in graft MHC expression may enhance immunogenicity and increase the rejection response.

Animals↗

PubMed1996

Single or bilateral lung transplantation for emphysema?

BACKGROUND: Most programs favor single lung transplantation for emphysema. However, this is controversial, and we have favored bilateral lung transplantation, confining single lung transplantation mainly to use in older patients and those of small stature. METHODS: A retrospective analysis was done of 119 consecutive lung transplantation procedures for emphysema at Barnes Hospital between 1989 and 1994 (50 single lung, 69 bilateral lung transplants) to (1) identify outcome differences between the two groups and (2) define the appropriate role of these two procedures. RESULTS: The single lung transplantation group was older and had a higher proportion of female patients. However, baseline pulmonary function (forced expiratory volume in 1 second), arterial oxygen tension, and exercise tolerance (6-minute walk distance) were similar. After transplantation, 90-day mortality (single lung transplantation 10% versus bilateral lung transplantation 7.2%; p = 0.74) and duration of mechanical ventilation, intensive care unit stay, and hospitalization were similar. Both groups achieved a significant and sustained improvement in forced expiratory volume, arterial carbon dioxide tension, arterial oxygen tension, and exercise tolerance within 3 months. However, the improvements in forced expiratory volume, arterial oxygen tension, and exercise tolerance were consistently significantly better in recipients of bilateral transplants at and beyond 6 months. Obliterative bronchiolitis was equally prevalent in both groups. Survival was similar but showed a trend toward better late survival in recipients of bilateral transplants (5-year actuarial survival: bilateral lung transplantation 53% versus single lung transplantation 41%). CONCLUSIONS: We conclude that (1) both procedures are satisfactory options in emphysema, producing durable results; (2) bilateral lung transplantation is not associated with increased operative mortality or morbidity and achieves superior improvements in spirometry findings, oxygenation, exercise tolerance, and possibly late survival; and (3) the superior improvements in function (and late survival) after bilateral lung transplantation may be attributed to the presence of more pulmonary reserve after the onset of obliterative bronchiolitis.

Actuarial Analysis↗

PubMed1996

Pulmonary retransplantation: does the indication for operation influence postoperative lung function?

OBJECTIVE: An international series of pulmonary retransplantation was updated to determine the factors associated with pulmonary function, bronchiolitis obliterans syndrome stage, and survival after operation. METHODS: One hundred sixty patients underwent retransplantation in 35 centers from 1985 to 1995. Logistic regression methods were used to determine variables associated with 3-month and 2-year survival after retransplantation. Values of forced expiratory volume in 1 second were contrasted between groups by unpaired, two-tailed t tests. RESULTS: The median follow-up in surviving recipients was 780 days. Actuarial survival was 45% +/- 4%, 41% +/- 4%, and 33% +/- 4% at 1, 2, and 3 years, respectively. On multivariable analysis, the only predictor of 3-month survival was preoperative ambulatory status (p = 0.005), whereas center experience with at least five pulmonary retransplantations was the sole predictor of 2-year survival (p = 0.04). The prevalence of stage 3 (severe) bronchiolitis obliterans syndrome was 12% at 1 year, 15% at 2 years, and 33% at 3 years after retransplantation. Retransplant recipients with stage 3 bronchiolitis obliterans syndrome at 1 year had a significantly worse actuarial survival than those with stages 0 to 2 (p < 0.01). By 3 years after retransplantation, the forced expiratory volume in 1 second was significantly lower in patients who underwent reoperation because of obliterative bronchiolitis than in patients who underwent retransplantation because of acute graft failure or an airway complication (p = 0.02). Only 31% of patients who underwent retransplantation because of obliterative bronchiolitis were free of bronchiolitis obliterans syndrome at 3 years versus 83% of patients who underwent retransplantation because of other indications (p = 0.02). CONCLUSIONS: Preoperative ambulatory status predicts early survival and center volume predicts intermediate-term outcome after retransplantation. Improved management strategies are necessary to prevent the development of progressive graft dysfunction after retransplantation for obliterative bronchiolitis.

Actuarial Analysis↗

PubMed1996

Nicorandil, a potent adenosine triphosphate-sensitive potassium-channel opener, ameliorates lung allograft reperfusion injury.

BACKGROUND: Lung allograft ischemia-reperfusion injury, characterized by increased pulmonary vascular resistance, pulmonary edema, and hypoxia, is the most frequent cause of early graft failure. Exogenous nitric oxide has been shown to reduce lung allograft reperfusion injury. During hypoxia, the adenosine triphosphate-sensitive potassium channel is an important ionic channel that links the bioenergetic metabolism to membrane excitability. It has been shown to play a critical role in vascular permeability and in activation of neutrophils and their subsequent interaction with vessel wall cellular components. The purpose of this study was to investigate whether nicorandil, a novel nitric oxide generator and adenosine triphosphate-sensitive potassium-channel opener, might enhance lung preservation and prevent allograft reperfusion injury. MATERIALS AND METHODS: Fourteen 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 right main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamics and arterial blood gas analysis (inspired oxygen fraction 1.0) were assessed for 6 hours before the dogs were put to death. After the assessment, activity of allograft myeloperoxidase and protein levels of bronchoalveolar lavage fluid were measured. Control animals (group I, n = 5) received no nicorandil. In group II (n = 5), the donor lung received nicorandil (24 mg/L) in the flush solution. In addition, recipient animals received nicorandil (0.5 mg/kg, intravenously) just before reperfusion, as well as a continuous infusion (0.74 +/- 0.03 mg/kg per hour) during the 6-hour assessment period. In group III (n = 4), glibenclamide, a selective adenosine triphosphate-sensitive potassium-channel blocker, was administered 15 minutes before nicorandil administration to both donor and recipient. The animals in group III received nicorandil in the same regimen as group II. RESULT: Superior gas exchange and hemodynamics were observed in lungs receiving only nicorandil. Allograft myeloperoxidase activity and protein levels in bronchoalveolar lavage fluid were significantly reduced in group II. Glibenclamide eliminated the beneficial effects of nicorandil. CONCLUSIONS: Nicorandil administration in the flush solution and during the reperfusion period ameliorates lung allograft dysfunction, improves blood flow, and reduces pulmonary vascular resistance and myeloperoxidase activity in the transplanted lung. The present study suggests that nicorandil reduces lung allograft reperfusion injury. The beneficial effects of nicorandil may be attributed to its properties as an adenosine triphosphate-sensitive potassium-channel opener.

Animals↗

PubMed1996

Results of 150 consecutive bilateral lung volume reduction procedures in patients with severe emphysema.

Between January 1993 and February 1996, we performed 150 bilateral lung volume reduction procedures for patients with severe emphysema. Patients were selected on the basis of severe dyspnea, increased lung capacity, and a pattern of emphysema that included regions of severe destruction, hyperinflation, and poor perfusion. Twenty percent to 30% of the volume of each lung was excised with the use of a linear stapler and bovine pericardial strips attached to buttress the staple line. Patients were between 36 and 77 years old, with an average 1-second forced expiratory volume of 25% of predicted, total lung capacity of 142% of predicted, and residual volume of 283% of predicted. Ninety-three percent of patients required supplemental oxygen, continuously or with exertion. All patients but one were extubated at the end of the procedure. The 90-day mortality was 4%. Hospital stay progressively decreased with experience, and for the last 50 patients the median hospital stay was 7 days. Prolonged air leakage was the major complication. Results at 6 months show a 51% increase in the 1-second forced expiratory volume and a 28% reduction in the residual volume. The Pao2 increased by an average of 8 mm Hg, and 70% of the patients who had previously required continuous supplemental oxygen no longer had this requirement. The improvements in measured pulmonary function were paralleled by a significant reduction in dyspnea and an improvement in the quality of life. Reevaluation at 1 year and 2 years after operation showed the benefit to be well maintained. We conclude that lung volume reduction offers benefits not achievable by any means other than lung transplantation for highly selected patients with severe emphysema.

Adult↗

PubMed1996

Effects of inflation volume during lung preservation on pulmonary capillary permeability.

UNLABELLED: The degree of lung allograft inflation during harvest and storage may affect posttransplantation function. High volume ventilation causes pulmonary vascular injury and increased pulmonary capillary permeability. However, the effect of lung inflation on pulmonary capillary permeability after hypothermic flush and storage is unknown. The current study was designed to examine the effects of hyperinflation and hypoinflation during preservation on pulmonary vascular permeability. METHODS: An isolated, ex vivo rabbit lung gravimetric model without the confounding effects of reperfusion was used to determine post pulmonary capillary filtration coefficients (Kf). New Zealand White rabbits (2.75 to 3.15 kg) were intubated and lungs ventilated with room air (tidal volume 25 ml). After sternotomy and heparinization, the pulmonary artery was flushed with low potassium dextran-1% glucose solution (200 ml). The heart-lung block was then excised. Two studies were conducted. For measurement of changes in airway pressure and lung volume during preservation, lungs were inflated to one of four storage volumes (12, 25, 40, 55 ml) with room air, 100% O2, or 100% N2 and stored at 10 degrees C in a sealed container filled with saline solution. During preservation, lung volume and airway pressure were measured at 3, 6, 12 and 24 hours. In the Kf study, lungs were inflated with 100% O2, 50% O2 (with 50% N2), or room air and preserved. After 24 hours of preservation at 10 degrees C, the heart-lung block was suspended from a strain-gauge force transducer and the lungs were ventilated with room air. The pulmonary artery was connected to a reservoir of hetastarch solution (6% hetastarch with 0.9% saline solution). Lung weight gain, airway pressure, pulmonary artery pressure, and left atrial pressure were measured continuously. After a brief flush with hetastarch solution, the reservoir was then elevated to achieve 1.0 to 1.5 mm Hg increments in pulmonary artery pressure. RESULTS: The slope of subsequent steady-state lung weight gain was used to determine the Kf. The current study demonstrated the following: (1) changes in lung volume and airway pressure during storage increased with intraalveolar O2 concentration, (2) irrespective of inflation, fraction of inspired oxygen, hyperinflation during lung preservation increased the Kf in a volume-dependent fashion; (3) Kf was increased in lungs stored hypoinflated with room air; and (4) at any inflation volume, the Kf was significantly increased with 100% O2 inflation after 24 hours of preservation. CONCLUSION: These results suggest that storage at high lung volume or high inspired oxygen fraction increases pulmonary capillary permeability.

Animals↗

PubMed1996

Hyperinflation of canine lung allografts during storage increases reperfusion pulmonary edema.

The optimal state of inflation for lung allografts during preservation is not known. We previously showed that hyperinflation of canine lung allografts during storage improved posttransplant graft function as measured during 10 minutes of contralateral pulmonary artery occlusion. However, we have also shown that hyperinflation during storage increases pulmonary capillary permeability. It is possible that short-term total cardiac perfusion through the transplanted left lung (for assessment) may not adequately reproduce the clinical situation. The purpose of this study was to assess the effects of hyperinflation during storage in a canine left single-lung transplantation model in which all perfusion was continuously directed to the graft after implantation. Twenty canine left single-lung transplants were done. The lungs of donor animals were ventilated at a tidal volume of 750 ml and an inspired oxygen fraction of 100%. Donor lungs were flushed with modified Euro-Collins solution and the trachea occluded at end inspiration. For donors in groups I and III, the trachea was sealed at that postinflation volume. In groups II and IV, 200 cc of air was withdrawn from the endotracheal tube under positive pressure and the trachea sealed at the lower tidal volume. Lungs were then extracted and stored at 1 degree C for 12 hours. After the preservation period, left lung transplants were performed. After implantation in all groups, the right pulmonary artery was ligated. In groups I and II, the right bronchus was ligated and in groups III and IV the right bronchus was kept open. Subsequent allograft gas exchange and hemodynamics were assessed during a 6-hour period of reperfusion. After assessment, both lungs were excised, wet/dry lung weight ratio was calculated, and histologic examination was done. During the 6-hour assessment, lungs stored in a state of hyperinflation (groups I and III) showed rapid deterioration of gas exchange. At the final assessment, arterial oxygen tension and alveolar-arterial oxygen gradient of groups I and III were significantly worse than those of groups II and IV (group I versus group II: arterial oxygen tension 87.5 +/- 15.0 versus 373.8 +/- 65.5 mm Hg, alveolar-arterial oxygen gradient 564.4 +/- 13.2 versus 298.6 +/- 69.3 mm Hg, p < 0.05; group III versus group IV: arterial oxygen tension 245.4 +/- 33.0 versus 543.6 +/- 41.8 mm Hg, alveolar-arterial oxygen gradient 392.5 +/- 35.6 versus 120.5 +/- 34.7 mm Hg, p < 0.01). We conclude that donor lung hyperinflation during storage does not provide better posttransplant allograft function when perfusion is limited only to the allograft.

Animals↗

PubMed1996

Inhaled nitric oxide improves lung allograft function after prolonged storage.

Morbidity caused by early allograft dysfunction, manifested by a progressive increase in pulmonary vascular resistance and a decrease in oxygenation, remains a serious problem in lung transplantation. Inhalation of nitric oxide, an essential homeostatic molecule, has been shown to have beneficial effects on a variety of acute lung injuries. The purpose of the present study was to investigate the effect of inhaled nitric oxide on posttransplant function of canine left lung allografts. Fourteen dogs underwent left lung allotransplantation. Donors received systemic heparin and prostaglandin E1 followed by pulmonary artery flush with modified Euro-Collins solution. Donor left lungs were stored for 18 hours at 1 degree C and subsequently implanted. Immediately after reperfusion, the contralateral right main pulmonary artery and bronchus were ligated. The chest was closed and recipients turned to the supine position for the 6-hour assessment period. Hemodynamic and arterial and venous blood gas analyses were made at 15-minute intervals at an inspired oxygen fraction of 1.0 and 5 cm of water positive end-expiratory pressure. Animals were killed at the end of the assessment. Allograft myeloperoxidase activity assays and wet/dry weight ratios were done. In group I (n = 5), nitric oxide gas was administered continuously at concentrations of 60 to 70 ppm before reperfusion and throughout the 6-hour assessment period. In group II (n = 5), nitric oxide administration was initiated at the same concentration after reperfusion injury had developed. Group III animals (n = 4) received no nitric oxide. Significant improvement in gas exchange was apparent in group I. At the end of the 6-hour assessment period, mean arterial oxygen tension was 253.8 +/- 44.7 mm Hg and 114.9 +/- 25.5 mm Hg in groups I and III, respectively (p < 0.05). Group II animals had no improvement in oxygenation with nitric oxide. Systemic hemodynamics were unaffected by nitric oxide. However, an immediate decrease in pulmonary vascular resistance was noted. Group I myeloperoxidase activity was significantly lower than that in control group III (0.24 +/- 0.06 versus 0.36 +/- 0.04 units, respectively; p < 0.05).

Administration, Inhalation↗

PubMed1996

Inhaled nitric oxide reduces human lung allograft dysfunction.

OBJECTIVE: Early severe graft dysfunction, as manifested by hypoxia and pulmonary hypertension, occurs in 10% to 20% of lung transplant recipients. We retrospectively investigated whether inhaled nitric oxide would reduce human lung allograft dysfunction by comparing postoperative hemodynamic data, gas exchange, and outcome in lung transplant recipients with early graft dysfunction treated with or without nitric oxide. METHOD: Among 243 adult lung transplant procedures, there were 32 patients (13.2%) in whom immediate severe allograft dysfunction developed (arterial oxygen tension/inspired oxygen concentration ratio <150). Group 1 (n = 17) included patients who underwent transplantation before nitric oxide became available in our center and were treated conventionally. Group 2 (n = 15) included those treated with nitric oxide as soon as severe allograft dysfunction was diagnosed. Duration of nitric oxide therapy (20 to 60 ppm) was 15 to 217 hours (average 84 hours). RESULTS: In group 2, nitric oxide lowered mean pulmonary artery pressure from 30 +/- 2 to 26 +/- 2 mm Hg (p < 0.05), improved the ratio of arterial oxygen tension to inspired oxygen fraction from 88 +/- 10 to 153 +/- 30 (p < 0.05) within 1 hour, and caused a sustained improvement in these parameters during extended therapy. Mean arterial pressure and cardiac index were unchanged during nitric oxide therapy. Transient methemoglobinemia (>6%) developed in two patients. However, no complications were associated with nitric oxide use. Duration of mechanical ventilation was 17 +/- 5 days in group 1 and 12 +/- 3 days in group 2. Four patients had airway complications in group 1, whereas no airway complication was encountered in group 2. Mortality was 24% (4/17) in group 1 and 7% (1/15) in group 2. CONCLUSION: Nitric oxide improves oxygenation and decreases pulmonary artery pressure without systemic circulatory effects in patients with severe allograft dysfunction. Furthermore, in these patients, nitric oxide may shorten postoperative mechanical ventilation time and reduce airway complications and mortality.

Administration, Inhalation↗

PubMed1996

Comparison of early functional results after volume reduction or lung transplantation for chronic obstructive pulmonary disease.

BACKGROUND: Bilateral lung volume reduction is designed to improve pulmonary function in selected patients with severe emphysema by improving diaphragmatic and chest wall mechanics. Early results of lung volume reduction suggest significant improvement to selected patients with chronic obstructive pulmonary disease, some of whom might otherwise be considered for lung transplantation. The purpose of this review was to compare intermediate results of volume reduction with single and bilateral lung transplantation. METHODS: Functional performance and survival after volume reduction were compared with single and bilateral sequential lung transplantation. After evaluation, patients were enrolled in a supervised intensive preoperative and postoperative program of pulmonary rehabilitation. Functional assessment, including pulmonary function tests, room air arterial blood gas analysis, and 6-minute walk distance, was obtained before the operation and 3, 6, and 12 months after the operation. RESULTS: Thirty-three patients underwent volume reduction (mean age 57 years), 39 patients single lung transplantation (55 years), and 27 patients bilateral lung transplantation (49 years). Early mortality was 0, 1 of 39, and 2 of 25 and mortality at 12 months was 1 of 33, 4 of 39, and 4 of 25 in the volume reduction, single, and bilateral lung transplantation groups, respectively. At 6 months, mean forced expiratory volume in 1 second was improved by 79% (volume reduction), by 231% (single lung transplantation), and by 498% (bilateral lung transplantation) over preoperative values. Exercise endurance as measured by 6-minute walk distance increased by 28% (volume reduction), by 47% (single lung transplantation), and by 79% (bilateral lung transplantation) from baseline. At 6 months, all patients having single or bilateral lung transplantation and 26 of 33 patients having volume replacement were free of supplemental oxygen. CONCLUSIONS: Although single and bilateral lung transplantation result in superior lung function, volume reduction achieves satisfactory improvement of disabling symptoms early after operation while avoiding immunosuppression and transplant-specific complications. Our experience suggests that (1) volume reduction is a suitable alternative in selected patients eligible for transplantation; (2) volume reduction provides an earlier option for treatment in patients who may require transplantation at some future date; (3) volume reduction is the only surgical treatment available to the many patients who are not current or future transplant candidates. Conversely, in patients not suitable for volume reduction, transplantation remains the only choice for surgical therapy.

Female↗

PubMed1996

Bronchial dehiscence after lung transplantation: correlation of CT findings with clinical outcome.

PURPOSE: To determine whether computed tomography (CT) can help predict which patients will require surgical or bronchoscopic intervention during healing of bronchial anastomotic dehiscence after lung transplantation. MATERIALS AND METHODS: The authors followed up 25 bronchoscopically proved dehiscent anastomoses through healing in 19 patients who underwent lung transplantation. CT findings were correlated with bronchoscopic results and clinical outcome. RESULTS: A bronchial defect and extraluminal air were initially present at CT in all 25 dehiscent anastomoses. Of 12 bronchial defects less than or equal to 4 mm, only one required intervention during healing (P < .05). Of 12 bronchial defects greater than 4 mm, six required intervention during healing. Eight of nine dehiscences with a tiny or small amount of extraluminal air healed with conservative treatment. Of 16 dehiscences associated with a moderate to large amount of extraluminal air, nine were treated conservatively and six required therapeutic intervention. Three healing anastomoses required bronchial stent placement. One patient died in the perioperative period. CONCLUSION: In patients with small dehiscences ( < 4mm) and patients with a tiny or small amount of extraluminal air, the anastomosis tends to heal without sequela. When patients have larger amounts of extraluminal air or larger ( > 4mm) dehiscences at presentation, CT cannot help predict which patients will require intervention.

Adolescent↗