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C L Bryan

Publications and source records attributed to C L Bryan.

12 recordsLinked to original sources

Ventilation-perfusion inequalities during graft rejection in patients undergoing single lung transplantation for primary pulmonary hypertension.

We report herein data on single lung transplant (SLT) recipients with primary pulmonary hypertension (PPH). One patient did well following surgery but died on the 30th postoperative day due to cytomegalovirus pneumonia. The remaining two patients initially did well with unlimited exercise tolerance following transplantation, but then developed marked dyspnea on exertion and hypoxemia on postoperative days 144 and 120, respectively. Pulmonary function testing showed marked deterioration of function and transbronchial lung biopsy specimens revealed acute graft rejection in one patient and evidence of chronic graft rejection in the second patient. Quantitative ventilation-perfusion lung scanning demonstrated a marked decrease in ventilation to the transplanted lung in both cases associated with only a mild decrease in perfusion. This V/Q mismatch resulted in markedly decreased arterial oxygen saturations, widened alveolar-arterial oxygen gradients, and clinically debilitating dyspnea. We conclude that rejection may result in significant V/Q mismatch and hypoxemia in PPH patients undergoing SLT, which may limit the use of this specific type of surgery for PPH.

Female

Effects of age on rat glutathione metabolism.

The authors hypothesized that rat plasma or tissue glutathione metabolism could change with age due to possible decreases in glutathione-related enzyme activities. To test this hypothesis, the authors measured plasma and tissue concentrations of glutathione and glutathione-related enzymes. Animals were 3 months, 12 months, or 24 months old at the time of experiments. Plasma glutathione was found to be significantly increased in both the 12-month-old and 24-month-old groups compared to the 3-month-old rats. Tissue enzyme measurements showed no significant differences between the groups in lung or liver glutathione peroxidase or glutathione S-transferase. gamma-Glutamyl transpeptidase activity was significantly decreased in kidney and lung with aging. Decreases in tissue gamma-glutamyl transpeptidase activity occur with age; this may contribute to increases in plasma glutathione concentrations.

Age Factors

Protection from hyperbaric oxidant stress by administration of buthionine sulfoximine.

To explore the role of glutathione in protecting rats from hyperbaric hyperoxia, we administered buthionine sulfoximine (BSO) to block gamma-glutamyl cysteine synthase activity and decrease tissue glutathione synthesis. We then exposed these animals and their vehicle-treated matched controls to 100% oxygen at 4 ATA or room air at 1 ATA. After BSO treatment, glutathione concentrations in air-exposed controls decreased 62% in lung, 76% in liver, 28% in brain, and 62% in plasma. Paradoxically, BSO-treated rats were protected from hyperbaric hyperoxia. The BSO-treated animals seized significantly later and had a markedly prolonged time of survival compared with the vehicle-treated controls. We conclude that BSO treatment protects rats from hyperbaric hyperoxia, despite its effects of lowering plasma and tissue glutathione concentrations. This protection may be related to a direct effect of the compound in decreasing free radical-mediated tissue injury, increasing tissue antioxidant defenses, or increasing seizure threshold.

Animals

Cardiopulmonary exercise responses after single lung transplantation for severe obstructive lung disease.

The purpose of this study was to characterize cardiovascular and ventilatory responses to exercise in single lung transplantation (SLT) recipients with nonseptic, severe obstructive lung disease (SLT-OB). We also investigated whether the hyperinflated native lung in SLT-OB recipients could limit normal increases in tidal volume by mechanically constraining the transplanted lung, resulting in ventilation-perfusion imbalance in the lung graft. Data from six SLT-OB recipients (five women, one man) and six age-matched SLT recipients (two women, four men) with severe interstitial lung disease (SLT-IN) were compared. Resting arterial O2 and CO2 tensions were normal and comparable between the SLT groups. Spirometry results were reduced but comparable between SLT groups. Total lung capacity was significantly larger in patients with SLT-OB than in patients with SLT-IN. Diffusion capacity was not different between SLT groups when differences in alveolar volume were accounted for. Quantitative perfusion to the lung graft was comparable between the SLT groups, but quantitative ventilation was greater in patients with SLT-OB than in patients with SLT-IN. Maximum exercise capacity following SLT-OB was decreased, but was comparable to that of SLT-IN recipients. None of the SLT-OB recipients reached predicted maximum minute ventilation and only one experienced mild arterial O2 desaturation, suggesting peripheral muscle abnormalities from corticosteroid use and deconditioning as limiting factors rather than a ventilatory limitation. Tidal volumes at end exercise in the SLT-OB recipients were normal. Our quantitative lung scan and exercise testing data suggest that ventilation-perfusion imbalance and resulting gas exchange abnormalities from lung graft constraint and compression do not occur at rest or with exercise after SLT for obstructive lung disease.

Anaerobic Threshold

Glutathione decreases the pulmonary reimplantation response in canine lung autotransplants.

The pulmonary reimplantation response (PRR) is a form of membrane permeability pulmonary edema occurring in lung transplants. The severity of the PRR reflects the quality and duration of lung graft preservation. Free radicals formed during ischemia with reperfusion in the autotransplanted dog lung may play a role in producing PRR. We hypothesized that the addition of reduced glutathione (GSH) to the preservative solution could decrease PRR if hydroperoxides are being formed. Six dogs underwent left lung autotransplantation after the lung was flushed with Euro-Collins solution (EC). These dogs demonstrated radiographic and histopathologic evidence of bilateral pulmonary edema, greatest in the transplanted left lung. They also had increases in lung wet to dry weight (W/D) ratios in both lungs (left, 12.0 +/- 0.9; right, 10.1 +/- 0.8) as compared with a group of five unmanipulated control animals (left, 6.0 +/- 0.5; right, 7.0 +/- 0.4). Malondialdehyde (MDA) concentrations were significantly increased in the transplanted left lungs (14 +/- 4) from this group as compared with the controls (5 +/- 7). Five additional dogs underwent left lung autotransplantation with GSH added to the EC cryopreservation fluid. These animals did not develop histologic or radiographic evidence of pulmonary edema, and W/D ratios as well as MDA concentrations were not different from those in controls. To evaluate the effect of ischemia alone on changes in lung GSH concentrations, ten additional dogs underwent left pneumonectomy. Left lungs were cryopreserved in EC + GSH. In five of the animals, the right lung was removed and preserved in EC alone. In the other five animals, the right lung remained in vivo for 3 h and was then removed. Lung GSH concentrations were doubled after 3 h of ischemia when incubated in EC + GSH compared to in vivo controls and to EC-treated lungs. These data suggest that GSH added to the preservation fluid prevents PRR following transplantation and that lung GSH concentrations actually increase during preservation prior to reimplantation and reperfusion if the lung graft is exposed to GSH in the preservation fluid.

Animals

Single lung transplantation. Alternative indications and technique.

Twenty-two patients have undergone 23 single lung transplants between March 1980 and April 1990 at the University of Texas Health Science Center at San Antonio. The actuarial survival rate is 77.27% at 12 months and 72.73% at 24 months. There have been no instances of bronchial dehiscence or stenosis, even though 13 of the patients were on a program of preoperative prednisone, every patient had high-dose perioperative methylprednisolone, and omental wraps were not used on any bronchial anastomosis. Of particular interest is the fact that three patients had primary pulmonary hypertension, three had secondary pulmonary hypertension, and 10 patients had chronic obstructive pulmonary disease, due in five cases to an alpha 1-antitrypsin deficiency. Each of these entities was previously thought to contraindicate single lung transplantation. Donor selection was based on an oxygen tension/inspired oxygen concentration ratio greater than 300, donor/recipient chest circumference within 3 inches, clear chest x-ray film, negative sputum Gram stain, and less than 6-hour estimated ischemic time. Harvest technique included donor prostaglandin E1 500 micrograms, topical slush, and pulmonoplegia with cold Euro-Collins solution. The heart and lung were separated in situ rather than the heart lung block being removed. A telescoping bronchial anastomosis was performed with 4-0 Prolene (not absorbable) sutures. We conclude that single lung transplantation has evolved into a simple operation, necessitating meticulous preoperative and postoperative care, which can be performed on a wide spectrum of critically ill patients with an acceptable mortality rate.

Adult

Single lung transplantation for primary pulmonary hypertension.

Single lung transplantation has become a therapeutic option for end-stage interstitial lung disease and obstructive lung disease. Our group recently extended this treatment to three patients with primary pulmonary hypertension. All patients had marked decreases in pulmonary artery pressures and pulmonary vascular resistance and increases in cardiac output following single lung transplantation. Spirometry, lung volumes, and diffusion capacity were not different in comparison to preoperative studies. Quantitative ventilation-perfusion scans revealed the majority of perfusion distributed to the transplanted lung, with ventilation approximately equally divided between the native and the transplanted lung. Despite ventilation-perfusion imbalance, there was no resting hypoxemia and there was no arterial oxygen desaturation with exercise. One patient expired on the 30th postoperative day due to cytomegalovirus infection of the lungs. In the remaining two patients, maximum exercise capacity following transplantation was near normal in one recipient and reduced in the second recipient. Of note, there was no evidence of ventilatory limitation or impaired oxygenation during exercise in these two recipients. Although an exaggerated exercise ventilatory response was present, this did not limit exercise performance. This report supports the use of single lung transplantation for the treatment of primary pulmonary hypertension.

Adult

Oxygen toxicity.

Ventilating patients with elevated oxygen tensions alters normal respiratory physiology and may damage lung tissue, depending on coexisting host and iatrogenic factors. Pulmonary oxygen toxicity begins at a cellular level when the generation of reduced oxygen intermediates exceeds local defenses. The mainstay of therapy is prevention. Supplemental oxygen should be prescribed at the lowest concentration possible that will still allow adequate tissue oxygenation. Presently, no specific therapeutic interventions are approved for use in humans to treat pulmonary oxygen toxicity. New agents that act as free radical scavengers or reduce free radical formation may prove useful in future clinical trials based on many of the scientific studies summarized in this review.

Animals

Species variation in lung antioxidant enzyme activities.

Exposure of several different animal models to O2-induced lung injury has revealed marked differences in sensitivity of various species to O2 damage. These differences may be due in part to variation of cellular antioxidant defenses. To characterize lung antioxidant enzyme activities in different species, we measured lung activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GSH S-trans) in rat, hamster, baboon, and human lung. Soluble lung fractions were also fractionated on Sephadex G-150-S columns and GSH-Px activity was measured using both cumene hydroperoxide and H2O2. This was done to evaluate non-Se-dependent GSH-Px activity in these lung samples. Human lung was obtained at surgery from patients undergoing lobectomy or pneumonectomy for localized lung tumors. SOD activity was similar for all four groups. GSH-Px activity was higher in rat lung than baboon or hamster lung. Lung CAT activity was variable with the highest activity present in the baboon which revealed a lung CAT activity 10 times higher than activity present in the rat. Lung GSH S-trans activities were higher in hamster, baboon, and human lung than in rat lung. Non-Se-dependent GSH-Px was present in rat lung but absent in hamster, baboon, and human lung. We conclude that the hamster was the best model of the animals studied for mimicking human lung antioxidant enzyme activities. Rat lung antioxidant enzyme activities were markedly different from any of the other species examined.

Animals

Transbronchial needle aspiration in the diagnosis of bronchogenic carcinoma.

Transbronchial needle aspiration (TBNA) was performed as a diagnostic procedure in 91 consecutive patients ultimately proven to have bronchogenic carcinoma. Results of TBNA were compared, in the same patients, to the diagnostic yield of cytologic examination of sputum, endobronchial brushings and washings, and endobronchial/transbronchial biopsy. The diagnostic yield for sputum was 13 percent (10 of 75); brushings, 40 percent (34 of 84); washings, 29 percent (26 of 89); biopsy, 56 percent (42 of 75); and TBNA, 45 percent (41 of 91). Aspirates were positive in 35 percent of patients with adenocarcinoma, 41 percent with squamous cell carcinoma, 52 percent with large cell undifferentiated carcinoma, and 55 percent of patients with small cell carcinoma. Carinal aspirates were positive in 54 percent (6 of 11); paratracheal aspirates, 57 percent (13 of 23); parabronchial aspirates, 39 percent (11 of 28); endobronchial, 78 percent (7 of 9), and peripheral mass or solitary pulmonary nodule, 40 percent (17 of 42). The overall diagnostic yield for brushings, washings, and biopsy was 64 percent. The addition of TBNA increased the yield to 71 percent. Bronchogenic carcinoma was diagnosed solely by TBNA in six patients, all with extrabronchial or extratracheal lesions. We conclude that TBNA increases the diagnostic yield of bronchoscopy, particularly in patients with extratracheal and extrabronchial lesions. An equally important observation is that TBNA fails to contribute significantly to the diagnosis of cancer in patients with lesions readily accessible by conventional bronchoscopic techniques. Exceptions to this observation include occasional patients with necrotic endobronchial tumors, submucosal lesions, and rarely patients with peripheral lung nodules or masses.

Adenocarcinoma

Transbronchial needle aspiration staging of bronchogenic carcinoma.

Transbronchial needle aspiration (TBNA) has been advocated as a reliable technique in the nonsurgical staging of patients with bronchogenic carcinoma. Some have questioned the reliability of TBNA, however. We used TBNA directed by computed tomography (CT) in 88 consecutive patients with bronchogenic carcinoma who had undergone chest CT. Chest CT was 94% sensitive, 79% specific, and 85% accurate in evaluating the mediastinum for malignant lymphadenopathy. There were 19 malignant aspirates in 44 patients with malignancy and apparent adenopathy evaluated by chest CT. No malignant carinal aspirates were obtained in any patient with a normal mediastinum evaluated by chest CT. There were 2 false positive needle aspirates. One patient with apparent right paratracheal adenopathy and malignant needle aspirate had no mediastinal neoplasm detected at surgery. The other false positive aspirate had been contaminated by tracheal debris. The overall sensitivity, specificity, and accuracy of TBNA mediastinal staging were 50, 96, and 78%, respectively. We conclude that CT scanning is a useful adjunct in the staging of patients with bronchogenic carcinoma, and that TBNA is a sensitive and highly specific staging technique that may negate the need for surgical staging in a large number of patients with bronchogenic carcinoma.

Adenocarcinoma