Treatment Of Pulmonary Vascular Disease Research Articles

Protein Oxidation and Nitrotyrosine formation in Tracheal Aspirate fluids of Mechanically Ventilated Neonates exposed to Hyperoxia and/or Inhaled Nitric Oxide † 1182

Elevated O2 tensions are employed in the treatment of pulmonary insufficiency, and inhaled nitric oxide (NO) is used for treatment of pulmonary vascular disease. Although useful, both of these drugs are potentially reactive chemicals that may cause significant adverse effects, most probably through oxidation or nitration of critical tissue molecules. The purpose of the present study was to test the hypothesis that oxidized proteins, assessed by western analysis after derivatization with 2,4-dinitrophenylhydrazine (DNPH), or nitrotyrosine-containing proteins could function as biomarkers of the respective oxidations. Identification of the specific proteins and modifications would provide important insight into the mechanisms responsible and the biomarkers could be used to guide efforts to minimize the adverse effects of these therapies. Three groups of infants born at greater than 36 wk and mechanically ventilated were studied. Infants were ventilated with: 1) 60% O2; and 3) NO, which is preceded by 100% O2. Tracheal aspirate fluids were obtained by suctioning, at times indicated clinically, and aliquots were frozen at -70oC and analyzed by treatment with DNPH, separation by SDS-PAGE, and probed with anti-DNP antibodies. Anti-nitrotyrosine antibodies were employed in samples not treated with DNPH. The major fractions of both modes of protein oxidation were observed uniformly in proteins migrating at molecular weights >87 kDa. In infants ventilated with hyperoxia, the anti-nitrotyrosine-reactive proteins were higher than in infants ventilated with room air in initial samples, but levels in the former group fell during the first week of life, whereas in the latter group the levels did not change markedly. Surprisingly, infants exposed to inhaled NO studied to date showed no distinctly greater levels or differences in distribution of nitrated proteins. The highest levels were observed in the initial sample from each child, with decreases through the first week of life. In infants that required longer ventilation, increased levels of DNPH-reactive proteins were observed. These studies indicate that NO therapy in neonates does not necessarily increase protein oxidation or nitration markedly, and that prolonged mechanical ventilation may contribute significantly to protein oxidation in these infants.

Lung transplantation.

Solid-organ transplantation has flourished during the last decade, with transplantation of heart and lungs becoming available to patients with end-stage cardiac or pulmonary diseases. The first lung transplant was performed in 1963 on a 58-year-old man with bronchogenic carcinoma. He survived for 18 days. During the next two decades, approximately 40 lung transplant procedures were attempted without success. These early attempts at lung transplantation were unsuccessful because of the development of lung rejection, anastomotic complications, or infection in the transplant recipients. In the early 1980s, human heart-lung transplantation was successfully performed for the treatment of pulmonary vascular disease. After this procedure, single-lung transplantation for the treatment of end-stage interstitial lung disease and obstructive lung disease was developed. More recently, the technique of double-lung transplantation has come into existence. This article reviews various aspects of lung transplantation, including immunosuppression, lung graft preservation, the various surgical techniques and types of lung transplant procedures available, recipient and donor selection criteria, and postoperative care of the transplant recipient. In addition, infectious and noninfectious complications seen in this particular patient population, including acute and chronic rejection, will be discussed.

Birth Defects, Original Article Series: Vol VIII, No. 1 Feb 1972, Congenital Cardiac Defects—Recent Advances

This book consists of 15 articles contributed by 29 authors. Its editors are Daniel Bergsma and Sidney Blumenthal. The contributors have written about subjects in which they have special interest. The topics are presented in random order and are concerned with aspects of congenital heart disease. The diagnosis and treatment of pulmonary vascular disease are discussed by Dr. Julien Hoffman. Dr. Abraham Rudolph relates his observations on coarctation of the aorta in the fetal and neonatal periods. Dr. Norman Talner describes the adjustment in the neonate and young infant to a congenital cardiac defect. Dr. Dan McNamara et al present their experience in the management of total anomalous pulmonary venous return in the young infant. Dr. William Rashkind tells about the natural and unnatural history of transposition of the great vessels. Kiechel, Blumenthal, and Griffiths describe a syndrome of papillary muscle infarction and dysfunction in infants. Techniques in the