ABSTRACT
RATIONALE: Central airway stenosis (CAS) after lung transplantation has been attributed in part to chronic airway ischemia; however, little is known about the time course or significance of large airway hypoxia early after transplantation. OBJECTIVES: To evaluate large airway oxygenation and hypoxic gene expression during the first month after lung transplantation and their relation to airway complications. METHODS: Subjects who underwent lung transplantation underwent endobronchial tissue oximetry of native and donor bronchi at 0, 3, and 30 days after transplantation (n = 11) and/or endobronchial biopsies (n = 14) at 30 days for real-time polymerase chain reaction of hypoxia-inducible genes. Patients were monitored for 6 months for the development of transplant-related complications. MEASUREMENTS AND MAIN RESULTS: Compared with native endobronchial tissues, donor tissue oxygen saturations (Sto2) were reduced in the upper lobes (74.1 ± 1.8% vs. 68.8 ± 1.7%; P < 0.05) and lower lobes (75.6 ± 1.6% vs. 71.5 ± 1.8%; P = 0.065) at 30 days post-transplantation. Donor upper lobe and subcarina Sto2 levels were also lower than the main carina (difference of -3.9 ± 1.5 and -4.8 ± 2.1, respectively; P < 0.05) at 30 days. Up-regulation of hypoxia-inducible genes VEGFA, FLT1, VEGFC, HMOX1, and TIE2 was significant in donor airways relative to native airways (all P < 0.05). VEGFA, KDR, and HMOX1 were associated with prolonged respiratory failure, prolonged hospitalization, extensive airway necrosis, and CAS (P < 0.05). CONCLUSIONS: These findings implicate donor bronchial hypoxia as a driving factor for post-transplantation airway complications. Strategies to improve airway oxygenation, such as bronchial artery re-anastomosis and hyperbaric oxygen therapy merit clinical investigation.
Subject(s)
Bronchi/metabolism , Cell Hypoxia/genetics , Lung Diseases/surgery , Lung Transplantation , Postoperative Complications/genetics , Respiratory Insufficiency/genetics , Transplants/metabolism , Adult , Aged , Bronchi/blood supply , Bronchi/pathology , Constriction, Pathologic/genetics , Cystic Fibrosis/surgery , Female , Gene Expression , Heme Oxygenase-1/genetics , Humans , Idiopathic Pulmonary Fibrosis/surgery , Length of Stay , Lung Diseases, Interstitial/surgery , Male , Middle Aged , Necrosis/genetics , Oximetry , Prognosis , Pulmonary Disease, Chronic Obstructive/surgery , Real-Time Polymerase Chain Reaction , Receptor, TIE-2/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sarcoidosis, Pulmonary/surgery , Up-Regulation , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor C/genetics , Vascular Endothelial Growth Factor Receptor-1/genetics , Vascular Endothelial Growth Factor Receptor-2/geneticsABSTRACT
BACKGROUND: Repetitive eccentric loading results in muscle damage and subsequent changes in muscle stiffness and edema accumulation, which manifest as reduced joint range of motion and increased muscle cross-sectional area. The purpose of the study was to evaluate changes in shoulder range of motion and the infraspinatus cross-sectional area with repetitive eccentric contraction. METHODS: Twenty physically active participants performed 9 sets of 25 repetitions of eccentric external rotator contractions. The ultrasonographic measurement of the infraspinatus cross-sectional area, and shoulder internal/external rotation and horizontal adduction range of motion were measured before, immediately after, and 24h after the intervention. FINDINGS: Infraspinatus cross-sectional area significantly increased from baseline immediately after exercise (P<0.001), and remained elevated from baseline at the 24-hour follow up (P<0.001). Internal rotation and horizontal adduction range of motion did not change significantly between baseline and post-exercise (P>0.05), but were significantly decreased at the 24-hour follow up from the baseline (internal rotation: P<0.001, horizontal adduction: P<0.001) and the immediate post-exercise (internal rotation: P=1.012, horizontal adduction: P=0.016). INTERPRETATION: These changes observed after the eccentric contractions may have implications for injury development in pitchers, because 1) the infraspinatus endures repetitive eccentric loading with pitching and 2) decreased internal rotation and horizontal adduction range of motion have been linked to upper extremity injuries. However, since the muscle response after eccentric loading varies by the task and previous exposure to similar stress, future study needs to investigate the time course of recovery of the muscle cross-sectional area and range of motion after pitching in competitive pitchers.