Biomedical subjects

G A Patterson

Publications and source records attributed to G A Patterson.

At least 127 records · Page 7Linked to original sources

PubMed1996

Site-specific responses to monocrotaline-induced vascular injury: evidence for two distinct mechanisms of remodeling.

Monocrotaline (MCT)-induced pulmonary vascular injury was used to begin studying the mechanism(s) of vascular remodeling in Fischer 344 rats, using extracellular matrix (ECM) gene expression to define areas of remodeling. By day 28 after injection, pulmonary artery pressures were increased and right ventricular hypertrophy had developed compared with normal controls. Tropoelastin, fibronectin, and alpha 1(I) procollagen mRNA levels increased at least 2-fold by day 28. In situ hybridization demonstrated tropoelastin gene expression by cells adjacent to the lumen and procollagen gene expression at the medial-adventitial border in both small muscular and large elastic pulmonary arteries. This pattern of gene expression was observed as early as 1 wk after MCT injury. These observations indicated two distinct areas of remodeling, one along the vascular lumen at the site of monocrotaline-induced injury and the other at a second distinct site. To determine whether other differences may be involved at these two sites, the presence of transforming growth factor-beta (TGF-beta) was studied. Total TGF-beta protein was 4-fold higher in remodeling lungs compared with normal lungs. Gene expression for all three isoforms of TGF-beta colocalized with tropoelastin gene expression along the vascular lumen but not with alpha 1(I) procollagen gene expression. These results suggest a complex site-specific response to injury mediated by two distinct pathways in this model of pulmonary vascular remodeling.

Animals↗

PubMed1996

A comparative study of thoracoscopic vs open removal of benign neurogenic mediastinal tumors.

STUDY OBJECTIVE: To assess the relative benefit of thoracoscopy vs open thoracotomy in the removal of benign neurogenic, mediastinal tumors (BNMTs). DESIGN: Retrospective comparative study of thoracoscopy and open thoracotomy. SETTING: Patients underwent surgery at the thoracic surgical services of two institutions from 1988 to 1994. Patients who underwent thoracoscopy were operated on more recently, 1992 to 1994. Patients who had thoracotomies underwent resection from 1988 to 1992. PATIENTS: All adult patients undergoing isolated removal of BNMTs at both institutions were included. Eleven patients underwent removal by posterolateral thoracotomy while six patients underwent thoracoscopic removal. INTERVENTIONS: BNMTs were removed by standard posterolateral thoracotomy or by three-hole thoracoscopic techniques with extension of incisions and conversion to an open procedure as necessary. MEASUREMENTS AND RESULTS: Larger tumors were more difficult to remove thoracoscopically. Two cases of transient postoperative ptosis were noted among the patients who underwent thoracoscopy. Operative time was longer in the thoracoscopy group (171 vs 112 min; p<0.05). Postoperative stay was significantly shorter (2.6 vs 4.5 days; p<0.02) and return to work tended to be more rapid (4.3 vs 7.7 weeks; p=0.13) among patients who underwent thoracoscopy. CONCLUSIONS: Thoracoscopic resection of BNMTs can be achieved safely and effectively with more rapid postoperative recovery when compared with an open thoracotomy approach to these mediastinal tumors.

Adult↗

PubMed1996

Smoking cessation and lung cancer resection.

STUDY OBJECTIVE: This study was designed to examine the extent of smoking cessation prior to thoracotomy for resection of a pulmonary malignancy and the recidivism rate. DESIGN: Prospective, longitudinal study. PATIENTS: All patients presenting to the General Thoracic Clinic. RESULTS: The study included 362 patients, with an average age of 64.7 years; 95% with a smoking history were followed up for an average of 17.5 months. Five surgeons in the same practice group performed the procedures: pneumonectomy, 45; lobectomy, 288; and lesser resections, 29. Forty-two percent of patients had quit prior to 1 year; 6% quit 3 months to 1 year; 15% quit between 2 weeks to 3 months; 12% quit at 2 weeks; and 19% continued to smoke up to surgery. Postoperatively, 86% of previously smoking patients were nonsmoking; 13% of patients started smoking again. Of the restarted smoking patients, 61% had never quit preoperatively. Only 59% of smoking patients admitted that a physician had ever told them to stop smoking; however, 89% of patients who were smoking postoperatively acknowledged physician advice to stop smoking. CONCLUSIONS: Long-term smoking cessation occurs in a large proportion of patients after resection of lung cancer. The longer the patient is nonsmoking preoperatively, the more likely he or she is to remain nonsmoking postoperatively. Conversely, patients who do not quit preoperatively are at significant risk of continuing to smoke postoperatively.

Female↗

PubMed1996

Thoracic outlet syndrome: a current overview.

Thoracic outlet syndrome and the surgery associated with this diagnosis have a controversial reputation. The majority of patients with thoracic outlet syndrome seen in the context of the work place will have a multiplicity of components to their symptomatology, including multilevel nerve compression and muscle imbalance of the neck, shoulder, and back. Identification and conservative management of these problems make the necessity for surgery for thoracic outlet syndrome a rare event. Decompression of the brachial plexus, with or without first rib resection, is a technically demanding surgical procedure requiring expertise in peripheral nerve, vascular and thoracic surgery. Evaluation of these patients requires an understanding of neuromuscular physiology and chronic pain syndromes.

Cumulative Trauma Disorders↗

PubMed1996

Supraclavicular first rib resection.

A supraclavicular approach will facilitate brachial plexus decompression and first rib resection. It allows the surgeon a complete visualization of all the neurovascular elements and removal of the first rib. In particular, under direct vision, the most posterior aspects of the first rib can be easily visualized and removed. During this dissection, care is taken to preserve the supraclavicular nerves. The technique of opening the pleura to allow drainage into the pleural cavity rather than around the brachial plexus will decrease postoperative scarring around the neural elements. Similarly, gentle but early postoperative movement of the head, neck, and upper extremity is encouraged in order to minimize scar formation around the brachial plexus.

Humans↗

PubMed1996

Lung volume reduction surgery for severe emphysema.

Lung volume reduction surgery is designed to alleviate symptoms of breathlessness and improve the quality of life for selected patients with severe emphysema. By resecting hyperinflated, nonfunctional areas of the lung, thoracic volume is reduced, chest wall and diaphragmatic mechanics are improved, and ventilation to the remaining portions of lung is improved. The operative procedure is designed to obtain maximum improvement with the least possible risk. Early mortality (less than 90 days) has been 3%, all from respiratory complications. Late mortality (more than 90 days) has been an additional 2%. Refinements in operative technique, including use of continuous staple line excision buttressed by bovine pericardium, creation of apical pleural tents, and avoidance of suction the chest tubes, have led to a steady decline in hospital stay, with the current average of 11 days and a median of 7 days. Ninety-nine of the 100 patients have been extubated at the end of the procedure, thus avoiding the need for postoperative ventilatory assistance.

Animals↗

PubMed1996

[Lung volume reduction surgery in advanced emphysema--results of the Washington University, St. Louis].

The aim of lung volume reduction surgery is to alleviate the symptoms of severe emphysema and to improve the life quality of the patient. The appropriate candidates (approximately 20% of all emphysematic patients examined in our clinic) had considerable dyspnea, an increased lung capacity, and a heterogenous dissemination of the emphysema with regional destruction of the parenchyma, hyperinflation and poor perfusion. After preoperative physiotherapie with a specified rehabilitation aim, a resection of 20 to 30% of the total lung volume was performed via sternotomy. From January 1993 to February 1996, 150 patients underwent bilateral lung volume reduction (age range = 36 to 77 years). The mean forced expiratory volume in 1 s (FEV1) was preoperatively 25% of the predicted value, the total lung capacity (TLC) 142% and the residual volume (RV) 283%, 94% of these patients necessitated oxygen supply at rest or during exercise. The 90-day mortality was 4%. All patients except 1 were extubated immediately after operation. The median hospital stay was 10 days in the first 100 patients and 7 days in the last 50. An increase of the FEV1 by 51% and a decrease of the RV by 28% was observed 6 months after operation. The mean PaO2 was improved by 8 mm Hg while the percentage of oxygen dependent patients went down from 50 to 16%. In addition a raise of the perseverance capacity, a clear decrease of dyspnea and an improvement of the life quality were achieved. These results persist after 1 (n = 56) and 2 (n = 20) years after operation. Lung volume reduction leads to an improvement of the lung function, symptoms and the quality of life, which is superior to that achieved by maximal clinical intervention.

Adult↗

PubMed1996

[Bilateral volume reduction for surgical treatment of advanced lung emphysema].

Lung volume reduction (LVR) for advanced emphysema improves lung function and restores respiratory excursion of chest wall and diaphragm. Between January 1993 and February 1996, bilateral LVR via sternotomy was performed in 150 patients with an early mortality (< 60 days) of 2% (3/150). In 90 patients, FEV1 rose from 0.7 (24% pred.) preoperatively to 1.1 L (37% pred.) at 6 months (57% increase; p < 0.001). In the same interval, O2 requirements decreased during exercise from 95 to 46% of patients and from 50 to 16% of patients on continuous O2. After 1 (n = 54) and 2 (n = 15) years, the improvements in FEV1, pO2, 6-min walking distance, and dyspnea, and the reduction of TLC and RV remained stable. In selected patients, bilateral LVR results in marked improvement of emphysema-related disability and offers excellent palliation.

Carbon Dioxide↗

PubMed1995

Single lung transplantation for pulmonary hypertension. Single institution experience in 34 patients.

BACKGROUND: The present study considered the uniformity and durability of the cardiopulmonary response to single lung transplantation in patients with severe pulmonary hypertension, as well as its effect on length and quality of survival. METHODS AND RESULTS: Thirty-four patients with pulmonary hypertension underwent evaluation, single lung transplantation, and follow-up assessment between November 1, 1989, and June 1, 1994. Operative survival for the entire group of patients was reasonable, with 91% (31 of 34 patients) surviving and being discharged from the hospital following transplantation. The actuarial survival for these 34 patients at 1-, 2-, and 3-year follow-up was 78%, 66%, and 61%, respectively. In the subgroup of 24 patients with primary pulmonary hypertension (PPH), 96% (23 of 24) were successfully discharged from the hospital after transplantation. The actuarial survival for this isolated PPH subgroup at 1-, 2-, and 3-year follow-up was 87%, 76%, and 68%, respectively. The uniform, early posttransplant normalization of pulmonary vascular resistance and right ventricular ejection fraction appears to persist throughout the 4-year follow-up period. Despite a high prevalence of bronchiolitis obliterans, the majority of survivors remain in New York Heart Association functional class I or II and are employed. CONCLUSIONS: Single lung transplantation can be performed in patients with end-stage pulmonary vascular disease with reasonable expectations for a relatively low operative mortality; immediate, complete, and durable amelioration of pulmonary hypertension and right ventricular failure; and optimal use of limited donor organ supply.

Actuarial Analysis↗

PubMed1995

Immunostains for blood group antigens lack prognostic significance in T1 lung carcinoma.

Recent reports have suggested that the retention of blood group antigen expression on tumor cells may be an important prognostic factor for survival. From 1986 to 1991, 136 patients underwent operative resection for their T1 N0 non-small cell lung carcinoma. One hundred twenty tissue blocks were available for antigen testing, and the histologic types were as follows: adenocarcinoma (73 patients), squamous cell (39 patients), large cell/undifferentiated (7 patients), and mucoepidermoid (1 patient). Follow-up is complete for all patients (mean, 41 months). This distribution of patients among the blood groups was as follows: A, 56 (47%); O, 53 (44%); B, 9 (7.5%), and AB, 2 (1.7%). Immunostaining was performed for A, B, and H blood group antigens. The 5-year actuarial survival in the blood group A patients (53%) did not differ significantly from that in the blood group O patients (59%). Similarly, when tumors were examined for their respective antigens, no significant differences were found in the 5-year survival of either blood group A or O patients between the tumors that retain and those that lose blood group antigen expression. Retention or loss of blood groups A or O antigen expression does not predict survival in patients with early-stage lung carcinomas.

ABO Blood-Group System↗

PubMed1995

Pressure gradient across the pulmonary artery anastomosis during lung transplantation.

BACKGROUND: Perioperative monitoring of pulmonary artery (PA) pressures in lung transplant recipients is critical. This report characterizes an intraoperative gradient across the PA anastomosis in a series of patients undergoing bilateral sequential lung transplantation. METHODS: Hemodynamic measurements were obtained in a series of 10 patients before anesthetic induction, during one-lung ventilation/perfusion of the newly transplanted first lung with the PA catheter proximal and distal to the anastomosis and after arrival in the intensive care unit. The following measurements were recorded: central venous pressure, cardiac output, PA occlusion pressure, and systemic and pulmonary arterial pressures (systolic, diastolic, mean). RESULTS: Although a systolic pressure gradient of more than 10 mm Hg across the anastomosis was observed in all patients, there was a significant variation in systolic (13 to 59 mm Hg), diastolic (2 to 10 mm Hg), and mean (5 to 27 mm Hg) PA gradients. Mean proximal systolic PA pressure measurements (56.2 +/- 20.6 mm Hg) were greater when compared to measurements obtained distal to the anastomosis (28.6 +/- 10.1 mm Hg, p = 0.001) and to those obtained in the postoperative period (32.1 +/- 9.7 mm Hg, p = 0.004). CONCLUSIONS: The present study demonstrates that during single-lung ventilation and perfusion, the PA pressure measured proximally may not reflect accurately the pressure distal to the vascular anastomosis.

Anastomosis, Surgical↗

PubMed1995

Effect of ischemic injury on subsequent rat lung allograft rejection.

BACKGROUND: It has been suggested that the frequency and severity of allograft rejection may be related to the degree of allograft ischemia. The purpose of this study was to determine whether ischemic insult correlates with lung allograft rejection. METHODS: Forty-eight left lung transplants were performed from Lewis donor rats into F344 recipient rats. Allografts were divided into two groups based on the degree of ischemic insult. Transplantation was performed immediately (group 1, minimum injury) or after 18 hours of cold (1 degree C) preservation (group 2, severe injury). Allografts were evaluated radiographically based on aeration scores (0 = opaque to 6 = normal). Animals were randomly sacrificed on days 7, 14, or 21 for histologic and immunohistochemical evaluation of rejection. RESULTS: On postoperative day 3, significantly lower aeration score was demonstrated in group 2 (3.69 +/- 1.71) compared to group 1 (5.0 +/- 1.09) (p < 0.05) as a result of the difference in reperfusion injury. However, by day 7 and thereafter, there was no significant difference. Histologic rejection was present by day 7 and peaked at day 14 with no significant difference between groups. There was also no difference in CD4+, CD8+ infiltrating lymphocyte population or expression of class II major histocompatibility complex antigen on bronchial epithelium. CONCLUSIONS: We conclude that ischemic injury in rat lung allograft does not correlate with the onset or severity of rejection.

Animals↗

PubMed1995

Free radical-mediated vascular injury in lungs preserved at moderate hypothermia.

BACKGROUND: Early allograft dysfunction remains a frequently encountered problem in clinical lung transplantation. Lung ischemia-reperfusion injury is associated with increased vascular permeability, which may be due in part to oxygen (O2) free radicals. However, it is not clear whether O2 free radicals are produced during ischemia under storage conditions in clinical lung transplantation. METHODS: Using an isolated ex vivo rabbit lung model, we studied the effects of preservation temperature on pulmonary capillary filtration coefficient (Kf) and lipid peroxidation in rabbit lungs inflated with 100% O2 after preservation with or without the O2 free radical scavenger dimethylthiourea. New Zealand white rabbits weighing 2.7 to 3.1 kg were intubated and ventilated with room air or 100% O2 (tidal volume = 25 mL). After heparinization and sternotomy, the pulmonary artery was flushed with low-potassium-dextran-1% glucose solution (200 mL). The heart-lung block was excised, submerged, and stored for 24 hours at 1 degree or 10 degrees C. After 24-hour preservation, the heart-lung block was suspended from a strain-gauge force transducer and ventilated with room air. The pulmonary artery cannula was connected to a reservoir of hetastarch solution. The lungs were flushed briefly with the hetastarch solution, and the reservoir was raised sequentially at 8-minute intervals to achieve 1.0 to 1.5 mm Hg increments in pulmonary artery pressure. Lung weight gain, airway pressure, pulmonary artery pressure, and left atrial pressure were measured continuously. The slope of steady-state lung weight gain was used to determine Kf (g.min-1.cm H2O-1 x 100 g-1 wet weight). RESULTS: Twenty-four-hour lung preservation at both 1 degree and 10 degrees C increased Kf. A similar increase in Kf was observed in lungs stored at 1 degree C while inflated with 100% O2. However, a significant increase in Kf was observed when lungs inflated with 100% O2 were stored at 10 degrees C. This increase in Kf was ameliorated by dimethylthiourea. Thiobarbituric acid-reactive substance levels were increased in lungs stored at 10 degrees C while inflated with 100% O2. This finding was eliminated by dimethylthiourea. CONCLUSIONS: These results indicate that free radical injury occurs during the ischemic phase when lungs are stored at moderate hypothermia while inflated with 100% O2.

Animals↗

PubMed1995

Prevalence and outcome of bronchiolitis obliterans syndrome after lung transplantation. Washington University Lung Transplant Group.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the main cause of late morbidity and mortality in lung transplantation. This study was designed to accurately determine the prevalence of this syndrome of chronic lung allograft dysfunction (which is presumed to be due to chronic rejection). METHODS: A retrospective analysis was done of 212 consecutive lung transplantations performed at Barnes Hospital between July 1988 and March 1994 to characterize the prevalence and course of BOS. One hundred eighty-seven transplant recipients survived at least 3 months after transplantation, putting them at risk for BOS. Recipients free of BOS (group I) were distinguished from those with BOS (group II) based on the presence of declining spirometry (forced expiratory volume in 1 second persistently less than 80% of previous baseline) or histologic obliterative bronchiolitis in group II. RESULTS: There were 110 transplantations in group I (59%) and 77 in group II (41%). At follow-up, BOS was detected using the following criteria: declining forced expiratory volume in 1 second alone, 40 of 77 (52%); positive histologic results alone, 7 of 77 (9.1%); and both, 30 of 77 (38.9%). Declining spirometry was the most common initial sign of BOS onset (57 of 77, 74%). There were no differences between groups with respect to age, sex, indication for transplantation, or type of transplantation performed. The mortality rate was significantly higher with BOS (group II, 22 of 77 [28.6%] versus group I, 8 of 110 [7.3%]; p = 0.001) and was not related to either the type of transplantation performed or the indication for transplantation. Follow-up of group II (mean 35.1 months; range, 7.1 to 63.7 months) showed a delay until BOS onset (16.1 +/- 1.2 months); when BOS was fatal, death ensued within 11.5 +/- 2.4 months of its onset. Comparison of the first and last quartiles of recipients in this series (QTR1 versus QTR4, 53 patients in each) demonstrated a higher prevalence of BOS in QTR1 (24 with BOS of 43 at risk [55.8%] versus QTR4, 5 with BOS of 52 at risk [9.6%]; p < 0.001) and a worse BOS functional score in QTR1 (2.2 +/- 0.2 versus QTR4, 0.8 +/- 0.2; p = 0.007). CONCLUSIONS: (1) Bronchiolitis obliterans syndrome is truly a clinical syndrome, not simply a pathologic entity; (2) BOS displays considerable latency in onset and progression; (3) lung transplant recipients must therefore be followed up for a sufficient interval to determine the actual prevalence and mortality rate of BOS; and (4) the prevalence and mortality rates of BOS are higher than previously appreciated, exceeding 50% and 40%, respectively.

Adult↗

PubMed1995

Recurrence of obliterative bronchiolitis and determinants of outcome in 139 pulmonary retransplant recipients.

An international series of pulmonary retransplantation was updated to identify the predictors of outcome and the prevalence and recurrence rate of obliterative bronchiolitis after operation. The study cohort included 139 patients who underwent retransplantation in 34 institutions in North America and Europe between 1985 and 1994. Eighty patients underwent retransplantation because of obliterative bronchiolitis, 34 because of acute graft failure, 13 because of intractable airway complications, 8 because of acute rejection, and 4 because of other indications. Survivors were followed up for a median of 630 days, with 48 patients alive at 1 year, 30 at 2 years, and 16 at 3 years after retransplantation. Actuarial survival was 65% +/- 4% at 1 month, 54% +/- 4% at 3 months, 45% +/- 4% at 1 year, 38% +/- 5% at 2 years, and 36% +/- 5% at 3 years; nonetheless, of 90-day postoperative survivors, 65% +/- 6% were alive 3 years after retransplantation. Life-table and univariate Cox analysis revealed that more recent year of retransplantation (p = 0.009), identical match of ABO blood group (p = 0.01), absence of a donor-recipient cytomegalovirus mismatch (p = 0.04), and being ambulatory immediately before retransplantation (p = 0.04) were associated with survival. By multivariate Cox analysis, being ambulatory before retransplantation was the most significant predictor of survival (p = 0.008), followed by reoperation in Europe (p = 0.044). Complete pulmonary function tests were done yearly in every survivor of retransplantation and bronchiolitis obliterans syndrome stages were assigned. Eleven percent of patients were in stage 3 at 1 year, 20% at 2 years, and 25% at 3 years after retransplantation. Values of forced expiratory volume in 1 second decreased from 1.89 +/- 0.13 L early after retransplantation to 1.80 +/- 0.15 L at 1 year and 1.54 +/- 0.16 L at 2 years (p = 0.006, year 2 versus baseline postoperative value). Most of this decrease occurred in patients who underwent retransplantation because of obliterative bronchiolitis, whereas the pulmonary function of patients who underwent retransplantation because of other conditions did not significantly change. We conclude that survival after pulmonary retransplantation is improving. Optimal results can be obtained in patients who are ambulatory before retransplantation. Compared with recent data after primary lung transplantation, bronchiolitis obliterans syndrome does not appear to recur in an accelerated manner after retransplantation. As long as early mortality as a result of infection can be minimized, pulmonary retransplantation appears to offer a reasonable option in highly selected patients.

ABO Blood-Group System↗

PubMed1995

Improved airway healing after lung transplantation. An analysis of 348 bronchial anastomoses.

We evaluated various clinical factors to identify predictors of airway complication after lung transplantation. Two hundred twenty-nine consecutive single (n = 110) and bilateral (n = 119) lung transplants were done between September 1988 and August 1994. These 348 bronchial anastomoses were retrospectively analyzed. Airway complication that necessitated clinical intervention affected 33 anastomoses (9.5%) in 29 patients (12.8%). Satisfactory healing was achieved in 22 of these patients by conservative therapy such as one or a combination of dilation, stent, and laser. There were five deaths (2.2%) attributable to airway complications. One patient had an early postoperative death unrelated to airway complication and one patient has a recalcitrant bronchus intermedius stricture. Complication occurred more often in single-lung than in bilateral lung transplants (16/110, 14.4%, versus 17/238, 7.1%; p < 0.05). The use of a mattress suture (21/153, 13.7%) was associated with more frequent complications than was simple interrupted suture (8/122, 6.6%) or figure-of-eight suture (4/73, 5.5%) (p < 0.05). For patients in whom airway complications subsequently developed, the duration of postoperative mechanical ventilation was greater than that for those in whom an airway complication did not develop. The prevalence of airway complications as our program evolved was evaluated by separating the 229 transplants into three groups: phase I, the first 77 transplants; phase II, the next 76 transplants; and phase III, the most recent 76 transplants. The airway complication rate per anastomosis was significantly lower in phase III (5/126, 4.0%) than in phase I (12/110, 10.9%; p < 0.05) and phase II (16/112, 14.3%; p < 0.01). The majority of airway complications are successfully treated and rarely fatal. The recent reduction in prevalence of airway complications is likely a result of better maintenance immunosuppression and rejection surveillance.

Adult↗

PubMed1995

Inhibition of inducible nitric oxide synthase ameliorates rat lung allograft rejection.

Recently, the inducible isoform of nitric oxide synthase has been shown to be an important immunomodulation molecule in allograft rejection. We have observed the production of nitric oxide during rejection and the effect of nitric oxide synthase inhibition on allograft rejection in a rat lung transplant model. Rat left lung allotransplants were performed in two strain combinations: brown Norway-to-F344 (major histocompatibility complex incompatible); and Lewis-to-F344 (minor loci incompatible) as severe and mild rejection models respectively. Syngeneic F344-to-F344 transplants were performed as a negative control. Nitric oxide production during rejection was determined by measuring the recipient's serum nitrite/nitrate levels as a stable end product of nitric oxide. The progression of rejection was evaluated radiographically and the grade of rejection was determined histologically. After operation, recipients of allotransplantation were randomly divided into two groups and received either aminoguanidine (200 mg/kg, intraperitoneal every 6 hours), a potent inducible nitric oxide synthase inhibitor, or normal saline treatment. The levels of serum nitrite and nitrate in recipients increased in the early phase of rejection in both allotransplant combinations. However, in the terminal phase of rejection, the serum nitrite/nitrate level decreased significantly compared with the peak level in the brown Norway-to-F344 recipients. The serum nitrite/nitrate levels in the syngeneic transplant recipients were normal during the entire observation period. In aminoguanidine-treated animals, serum nitrite/nitrate levels remained normal in both allograft combinations. Significant suppression of rejection in aminoguanidine-treated recipients was observed histologically and radiographically in comparison with untreated recipients in the brown Norway-to-F344 combinations. In the Lewis-to-F344 combination, aminoguanidine treatment significantly ameliorated histologic rejection but did not affect radiologic appearance. We therefore conclude nitric oxide is produced during early allograft rejection and may prove to be a marker and mediator of early rejection. The inhibition of inducible nitric oxide synthase results in significant reduction in rat lung allograft rejection.

Animals↗

PubMed1995

Successful outcome of lung transplantation is not compromised by the use of marginal donor lungs.

Lung transplantation is limited by a shortage of suitable donors. To address this shortage, we have begun using donor lungs that do not meet all of our previous rigorous donor criteria. Of 133 consecutive lung transplants done between June 1991 and March 1994, 89 donors were considered ideal because they satisfied all of the following accepted donor criteria (group I): age younger than 55 years, smoking less than 20 pack-years, arterial oxygen tension greater than 300 mm Hg (using inspired oxygen fraction of 1.0 and positive end-expiratory pressure 5 cm H2O), and chest radiograph negative for infiltrate or trauma (contusion or pneumothorax). Thirty-seven donors failed to satisfy one of these criteria and seven donors failed to satisfy two of them, yielding 51 criteria denoting marginal status in the 44 donors in the marginal group (group II) as follows: age older than 55 years, 2; smoking history 20 or more pack-years, 9; unsatisfactory chest radiograph, 34; and arterial oxygen tension less than 300 mm Hg, 6. Sixty-three single lung transplants were done (group I, 44 versus group II, 19) compared with 70 bilateral sequential transplants (group I, 45 versus group II, 25). In 24 cases in group II, at least one of the lungs actually being implanted contained contusion or infiltrate. Evaluation of recipients from the two groups showed no significant difference in median duration of postoperative mechanical ventilation (3 days in both group I and group II) nor in alveolar-arterial oxygen gradient immediately after transplantation (group I, 304 +/- 14 mm Hg versus group II, 275 +/- 22 mm Hg; p = 0.266) or at 24 hours (group I, 125 +/- 12 mm Hg versus group II, 122 +/- 18 mm Hg; p = 0.933) (all values represent mean plus or minus the standard error). However, cardiopulmonary bypass was required to facilitate second graft insertion in bilateral sequential transplants more often in the marginal group (5 of 25, 20%) than in group I (6 of 45, 13%). There were three deaths within 30 days in group I (operative mortality, 3.4%) and none in group II. Currently, 74 (83.2%) of 89 remain alive in group I compared with 38 (86.4%) of 44 in group II. On the basis of these data, we conclude that successful outcome of lung transplantation can be achieved with the use of marginal donor lungs.

Age Factors↗