Perspectives on thoracoscopy in general thoracic surgery.
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Humans↗
Biomedical subjects
J D Cooper
Publications and source records attributed to J D Cooper.
Lung preservation with low-potassium dextran flush in a primate bilateral transplant model.
We used a bilateral lung transplant model to confirm, in primates, the results of lung preservation studies previously obtained in a canine single-lung transplant model. The donor lungs were flushed with low-potassium dextran solution and maintained semiinflated with 100% oxygen at 10 degrees C for a planned ischemic time of 12 hours for the lung implanted first. Of eight experiments performed, results in the 6 operative survivors form the basis of this report. After bilateral lung transplantation, animals were maintained on a ventilator for 6 hours; arterial oxygen tension, pulmonary artery pressure, and pulmonary vascular resistance were determined in the recipients at 2, 4, and 6 hours after transplantation and compared with donor values, which served as controls. Arterial oxygen tension in the recipients did not differ from the controls (p = not significant), whereas the pulmonary artery pressure and pulmonary vascular resistance showed significant elevation (p < 0.05 versus control values). After the 6 hours of assessment, the animals were extubated and 3 survived for 48 to 72 hours with a mean arterial oxygen tension of 69 mm Hg on room air. These results demonstrate excellent lung function after a minimum of 12 hours of preservation in a primate model in which the animal is totally dependent on the function of transplanted lung tissue, and confirm the potential for prolonged clinical lung preservation.
Animals↗
Central neuroanatomical organisation of the rat visuomotor system.
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Animals↗
Quantitative cultures of the cell fraction and supernatant of bronchoalveolar lavage fluid for the diagnosis of cytomegalovirus pneumonitis in lung transplant recipients.
Results of quantitative shell vial cultures of cell and supernatant fractions of bronchoalveolar lavage (BAL) fluid from lung transplant recipients were compared with results of transbronchial lung biopsies. Cytomegalovirus (CMV) was present in both the cell and supernatant fractions, including 28 (80%) and 29 (83%), respectively, of 35 BAL samples with corresponding biopsies that showed evidence of CMV pneumonitis and 34 (15%) and 75 (33%), respectively, of 227 BAL samples with corresponding biopsies that did not. Cultures of unseparated BAL fluid had a similar yield to cultures of supernatant. Virus titers of cell fractions and supernatants from BAL samples with corresponding biopsies that were positive for CMV pneumonitis were higher than those from BALs with negative corresponding biopsies. Culture of the unseparated fluid is recommended for simplicity and to maximize detection of CMV. Quantitative results may help in the identification of CMV pneumonitis, but additional studies are needed before quantitative cultures can be recommended for routine use.
Bronchoalveolar Lavage Fluid↗
Cytomegalovirus infection and pneumonitis. Impact after isolated lung transplantation. Washington University Lung Transplant Group.
Using aggressive surveillance of blood, bronchoalveolar lavage (BAL) fluid, and lung tissue, we sought to determine the incidence of cytomegalovirus (CMV) pneumonitis in isolated lung transplant recipients and to characterize its impact on pulmonary function, chronic rejection, and survival. Forty-six lung transplant recipients who survived greater than 30 days had prospective documentation of CMV infection in blood and BAL fluid and regular surveillance with transbronchial lung biopsy. CMV infection was documented in 92% of patients who were D-/R+, D+/R+, or D+/R-, and the incidence of histologically confirmed CMV pneumonitis among these patients was 75%. No D-/R- patient experienced CMV infection or disease. D+/R- patients experienced more frequent and severe episodes, and ganciclovir prophylaxis during the first 2 wk was not useful. CMV pneumonitis was accompanied by detectable radiographic changes in less than one third of cases. The detection of CMV in BAL fluid was not predictive of CMV pneumonitis on biopsy, except in D+/R- patients during the first 90 days after transplantation. There was no evidence of an adverse impact because of CMV infection on pulmonary function during the first year after transplantation. A relationship between CMV infection and bronchiolitis obliterans could not be documented; however, D+/R- patients had higher morbidity and a trend toward lower survival. In a multivariate analysis, D+/R- status was an independent predictor of death.
Adult↗
Neointimal macrophages colocalize with extracellular matrix gene expression in human atherosclerotic pulmonary arteries.
Vascular remodeling in adult atherosclerotic pulmonary arteries is characterized by discrete areas of neointimal extracellular matrix gene expression, suggesting regulation by local factors. Though the factors responsible for inducing matrix gene expression in atherosclerotic lesions are largely unknown, several observations suggest macrophages may be a focal source of those factors. Immunohistochemistry confirmed the presence of macrophages in the neointima of atherosclerotic elastic pulmonary arteries from patients with unexplained pulmonary hypertension. Areas of neointima containing dense clusters of macrophages were separated by sparsely populated areas. Foamy macrophages resided more deeply within the neointima than nonfoamy macrophages, which were found more often subjacent to the endothelium or within the lumenal one-third of the neointima. Combined immunohistochemistry-in situ hybridization indicated neointimal fibronectin and type I procollagen gene expression was intimately associated only with nonfoamy neointimal macrophages. These observations suggest that: (a) nonfoamy neointimal macrophages participate in the local regulation of extracellular matrix gene expression in atherosclerotic pulmonary arteries; (b) foamy macrophages, which are not associated with matrix gene expression, have undergone modulation of their secretory phenotype.
Arteriosclerosis↗
Current therapy for thymoma.
Thymomas are the most frequently encountered neoplasm of the anterior mediastinum. Thymic neoplasms can be divided into 3 broad categories based on histologic appearance and behavior. Thymomas are tumors with benign-appearing cellular features. If there is no gross or microscopic invasion beyond the capsule, the tumor is considered benign. Any tumor with gross or microscopic invasion through the capsule is considered malignant. In a third category, thymic tumors which have histologically malignant epithelial features, are considered thymic carcinomas and generally have an adverse prognosis. Microscopically, thymomas consist of a variable component of lymphocytic, epithelial, and fusiform (spindle) cell elements. The tumors may be classified according to the predominant cell type or are considered mixed if no cell type predominates. Prognosis is most strongly linked to clinical stage. The role of adjuvant radiotherapy or chemotherapy in the treatment of such tumors is controversial, but malignant thymomas are generally responsive to radiotherapy. Associated myasthenia gravis does not adversely affect the prognosis of thymoma, and medical attention to the myasthenia may contribute to earlier diagnosis of the thymoma. Cisplatin-based chemotherapy may be used to treat advanced disease with a modest response rate.
Adult↗
Evaluation of lung metabolism during successful twenty-four-hour canine lung preservation.
We used a canine left lung allotransplantation model to evaluate 24-hour lung preservation with two different electrolyte solutions, low-potassium dextran and low-potassium dextran with 1% glucose. To investigate changes in the energy status during preservation, we analyzed the lungs for adenosine triphosphate, phosphocreatine, and several metabolites of the glycolysis pathway and the citric acid cycle: glucose, glucose-6-phosphate, lactate, citrate, and malate. We also devised and evaluated a pulmonary cooling jacket to prevent rewarming of the lung during implantation. The lungs were divided into four groups. Groups I (n = 10) and II (n = 6) were flushed with low-potassium dextran and groups III (n = 6) and IV (n = 6) were flushed with low-potassium dextran solution with 1% glucose. The cooling jacket was used for groups II and IV only. After 24-hour preservation at 10 degrees C, the left lungs were implanted into the recipient animals. Function of the transplanted left lung was assessed during temporary (10 minutes) occlusion of the contralateral pulmonary artery while both lungs were ventilated with 100% oxygen. This assessment was performed at 1 hour and at 3, 8, and 22 days after transplantation. Immediately after transplantation the arterial oxygen tension was 279 +/- 70 mm Hg in group I, 376 +/- 56 mm Hg in group II, 523 +/- 41 mm Hg in group III, and 518 +/- 50 mm Hg in group IV. The arterial oxygen tension in groups III and IV were significantly greater than in group I (p < 0.05). Of the lungs preserved with low-potassium dextran solution with 1% glucose solution, 11 of 12 (92%) showed excellent lung function (arterial oxygen tension > 300 mm Hg) at 3 days; only 10 of 16 lungs preserved with low-potassium dextran achieved this level of function. Glucose, glucose-6-phosphate, lactate, citrate and malate levels decreased significantly during 24-hour preservation with low-potassium dextran solution; they were stable with low-potassium dextran solution with 1% glucose. Adenosine triphosphate and phosphocreatine were stable for 24 hours with both low-potassium dextran and low-potassium dextran solution with 1% glucose. The cooling jacket provided uniform cooling of the lung parenchyma during implantation, and significant increase in temperature was observed in its absence, with topical cooling by cold saline solution.(ABSTRACT TRUNCATED AT 400 WORDS)
Adenosine Triphosphate↗
Active collagen synthesis by pulmonary arteries in human primary pulmonary hypertension.
Immunohistochemistry was performed on lung tissue obtained from patients with severe unexplained pulmonary hypertension using an antibody to the amino-terminal end of the procollagen type I propeptide. This antibody identifies newly synthesized alpha I(I) procollagen before cleavage of the amino-terminal propeptide following secretion and, therefore, can identify sites of active collagen deposition. Procollagen was detected in the media, media and neointima, or neointima alone of a large number of small muscular arteries from hypertensive lungs. Normal adult lungs were negative. Neointimal cells in remodeled small muscular arteries stained positively for alpha-smooth muscle actin and desmin consistent with a smooth muscle lineage. These data suggest smooth muscle-like cells in small muscular arteries are actively synthesizing collagen in patients with severe unexplained pulmonary hypertension.
Actins↗
An update on the current status of lung transplantation: report of the St. Louis International Lung Transplant Registry.
There were 2,330 lung transplants reported to the St. Louis International Lung Transplant Registry as of September 1, 1993. The most common indication continues to be chronic obstructive pulmonary disease. The 1-, 2-, and 3-year actuarial survival statistics for all transplants were 68%, 59%, and 54%, respectively. Infection was the major cause of both early and late mortality, though in the latter situation, infection most often occurred in a setting of enhanced immunosuppression for chronic rejection.
Adolescent↗
Atrophy but not death of adult septal cholinergic neurons after ablation of target capacity to produce mRNAs for NGF, BDNF, and NT3.
The effect of unilateral excitotoxic ablation of hippocampal neurons was investigated on (1) the local production of mRNA for NGF and related neurotrophins, (2) the amount of NGF protein in the septal region, and (3) the viability and appearance of afferent septal cholinergic neurons in adult rats. After near complete ablation of hippocampal neurons, total levels of NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3) mRNA measured by quantitative Northern blot analysis in the hippocampal remnant fell significantly, to less than 25% of control values by 28 d and to less than 9% by 300 d. In the septal region ipsilateral to such lesions, NGF protein levels measured by ELISA fell significantly, to about 35% of control values, but the number of immunohistochemically detected cholinergic neurons did not decline significantly for up to 500 d. Instead, the cholinergic neurons persisted in an atrophied state, exhibiting severe shrinkage and reduced staining for the transmitter-synthesizing enzyme ChAT. The parameters of cell size and ChAT staining intensity correlated significantly with the amount of hippocampal tissue present. These findings indicate that in adult rats, target-derived NGF, BDNF, and NT3 do not regulate the survival of septal cholinergic neurons in proportion to the number of target neurons present. Moreover, the findings suggest that one or more of these target-derived neurotrophins regulate the structural and chemical phenotype of these neurons in the adult.
Animals↗
The donor lung: infectious and pathologic factors affecting outcome in lung transplantation.
The prevalence of posttransplantation pulmonary infection and the importance of this complication with respect to morbidity in patients undergoing lung transplantation is significant. Over a 1-year period, case histories of all patients undergoing lung transplantation at Barnes Hospital, Washington University, were reviewed to examine the importance of organisms isolated in the donor lung in the development of subsequent invasive infection in transplant recipients. Twenty-eight of 29 bronchial washings (97%) taken from donors before retrieval grew at least one organism. The most common organisms identified were Staphylococcus and Enterobacter. In 12 of these cases (43%), similar organisms were isolated from the tracheobronchial tree of the recipients, and 6 of these recipients (21%) subsequently had invasive pulmonary infections as a result of the organism originally isolated in the donor. We recommend that antibiotic coverage in transplant recipients should be initiated on the basis of Gram stain results and modified on the basis of cultures obtained from the donor lungs. Pathologic analysis of donor lung tissue taken before transplantation was available in 12 cases. Four donors had histologic evidence of established pneumonia in the donor lung, and infections then developed in the recipients. One other patient who received a lung that had widespread bone marrow emboli and subsequent infarction later had a complete anastomotic dehiscence. An additional patient had profound early donor lung dysfunction without any evidence of rejection or infection. Pathologic findings from the donor in this case demonstrated preexistent acute vasculitis with emboli. We suggest that as preservation techniques improve, the opportunities for closer scrutiny of donor lung tissue before implantation will become increasing desirable and feasible.
Hospitals, University↗
Changes in alveolar oxygen and carbon dioxide concentration and oxygen consumption during lung preservation. The maintenance of aerobic metabolism during lung preservation.
The lung is the only organ to which oxygen may be supplied after its blood supply is stopped. Before this study, we were not certain whether lung cells were able to maintain aerobic metabolism with the oxygen in the alveoli during preservation. Excised rabbit lungs were used to measure changes in the concentration of oxygen and carbon dioxide in the airway and changes in glucose, glucose-6-phosphate, lactate, adenosine triphosphate, and phosphocreatine levels in the lung tissue during preservation under different conditions. Twenty-seven lungs were flushed with low-potassium dextran electrolyte solution, inflated with room air, and preserved at 1 degree C (n = 8), 10 degrees C (n = 8), or 22 degrees (n = 11) for 4, 12, or 24 hours. Eight additional lungs were inflated with 100% nitrogen and preserved at 10 degrees C for 4 (n = 4) or 24 (n = 4) hours. Oxygen levels decreased and carbon dioxide levels increased in the airway of the lungs that were inflated with room air at rates dependent on the preservation temperature. The increase of carbon dioxide in the lungs that were inflated with 100% nitrogen was very small. When the oxygen was not available in the alveoli, lactate accumulated, and adenosine triphosphate and phosphocreatine decreased in the lung tissue. We concluded that lung cells are able to maintain aerobic metabolism with the oxygen in the alveoli during preservation and that the maintenance of aerobic metabolism may be essential to maintain the optimum viability of preserved lung tissue.
Adenosine Triphosphate↗
Pulmonary "twinning" procedure: use of lungs from one donor for single-lung transplantation in two recipients.
Since the introduction of lung transplantation as an option for patients with end-stage respiratory disease in the early 1980s, there have been substantial advances made in the technical aspects of transplantation as well as the early clinical results. With an ever-increasing number of patients being designated suitable candidates for transplantation, the volume of transplants in the foreseeable future will be limited more on the basis of donor lung supply than any other single factor. Pulmonary "twinning" provides an important step in ensuring that all suitable and available donor lungs are utilized whenever feasible. This report reviews the results of 20 single-lung transplantations carried out in five separate transplantation centers using organs retrieved from ten donors. The overall mortality rate in this group of patients was 5%, which compares very favorably with historical controls. No serious problem was noted with respect to increased perioperative morbidity or increased ischemic times in this group of patients. We suggest that this process should be considered and, wherever possible, adopted by all major lung transplant centers.
Adult↗
Management of dysfunction in the transplanted lung: experience with 7 clinical cases. Washington University Lung Transplant Group.
In a series of 34 lung transplant patients, donor lung dysfunction occurred on 7 occasions. One patient underwent retransplantation and the remaining 6 were treated conservatively. Survival was 100% in the donor lung dysfunction group. Percent predicted forced expiratory volume in 1 second, carbon monoxide diffusion, room air oxygen tension, and distance walked in 6 minutes were all lower (p less than 0.05) at 1 month after transplantation in those patients with donor lung dysfunction as compared with those without. These differences were not significant at 3 months after transplantation. We conclude that donor lung dysfunction can usually be managed conservatively with satisfactory results. Longer follow-up of this group of patients will be necessary to determine the long-term consequences of early graft injury.
Adult↗
Production and reversibility of right ventricular hypertrophy and right heart failure in dogs.
Combined heart-lung transplantation has been used for end-stage primary pulmonary hypertension. Experience with single-lung transplantation for other conditions suggested that associated severe right ventricular dysfunction resulting from increased afterload would recover after placement of a satisfactory lung allograft. Early experience with the application of single-lung transplantation for pulmonary hypertension supports this contention. We devised a reversible canine model of chronic progressive pressure-overloaded right heart failure by pulmonary artery banding to study the echocardiographic, hemodynamic, and pathological reversibility of the failing right heart. Clinical right heart failure was defined as the development of ascites and pleural effusions. Right heart failure developed in 23 dogs 67 to 348 days after banding, and they were divided into two groups to determine its early and long-term effects. Group 1 dogs (n = 11) were either sacrificed immediately after the onset of right heart failure (n = 5) or unbanded (n = 6); group 2 dogs (n = 12) were maintained in right heart failure for 3 months and then either sacrificed (n = 6) or unbanded. Unbanded dogs in both groups were observed for 4 additional months before sacrifice. A control group of 6 normal dogs was sacrificed for pathological comparisons. After unbanding, the right ventricular systolic pressure fell from 97 +/- 17 mm Hg (group 1) and 88 +/- 31 mm Hg (group 2) to 44 +/- 11 mm Hg and 47 +/- 13 mm Hg, respectively. Despite this persistent gradient across the pulmonary artery, echocardiographic and hemodynamic measures of right ventricular function returned to normal, albeit more slowly in the group 2 dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Failure of prophylactic ganciclovir to prevent cytomegalovirus disease in recipients of lung transplants.
In an effort to prevent cytomegalovirus (CMV) pneumonitis, seven consecutive CMV-seronegative lung transplant recipients of organs from seropositive donors (D+/R-) were given ganciclovir, 2.5-5 mg/kg intravenously twice daily for the first 10-21 days after transplantation, and commercial polyvalent immune globulin, 200-400 mg/kg every 7-14 days intravenously, for the first 2-3 weeks after transplantation. This regimen was followed by oral acyclovir. Six patients developed CMV viremia and all developed CMV pneumonitis. Viremia occurred later in these patients compared with D+/R- patients who received alternative forms of CMV prophylaxis or CMV-seropositive recipients who received no specific prophylaxis (P = .023 and P = .021, respectively). There was no statistical difference in incidence or time to onset of CMV pneumonitis. When given as described, prophylactic ganciclovir and immune globulin followed by oral acyclovir may have delayed CMV viremia but did not prevent it or pneumonitis in high-risk lung transplant recipients.
Acyclovir↗
Whence the lungs? A study to assess suitability of donor lungs for transplantation.
Efforts at clinical lung transplantation have been hampered by an insufficient donor pool. To estimate the number of potential suitable lung donors, we conducted a UNOS-sponsored survey of organ procurement organizations and collected data with respect to possible lung donation from human cardiac donors. Contact with OPOs was made by telephone after cardiac donors were identified by UNOS. Of 150 cardiac donors, 7 were utilized for lung or heart-lung transplantation. By our criteria, however, 47 additional donors had lungs that may have been suitable for transplantation but were not utilized, and frequently were not offered for transplantation for a variety of reasons. This survey implies that approximately 25% of cardiac donors likely have lungs that may be suitable for transplantation.
Adult↗