Research Topics
Genomes and Genes | Scott E SinclairSummaryAffiliation: University of Tennessee Country: USA Publications
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Publications
Augmented lung injury due to interaction between hyperoxia and mechanical ventilationScott E Sinclair
Departments of Medicine and Physiology, University of Tennessee, Memphis, TN 38163, USA
Crit Care Med 32:2496-501. 2004..Mechanical overdistension and hyperoxia can independently cause lung injury, yet little is known about their combined effects. We hypothesized that hyperoxia exacerbates lung injury caused by large tidal volume ventilation...- Therapeutic hypercapnia and ventilation-perfusion matching in acute lung injury: low minute ventilation vs inspired CO2Scott E Sinclair
Department of Medicine, University of Tennessee, 956 Court Ave, Room H314, Memphis, TN 38163, USA
Chest 130:85-92. 2006..We hypothesized the presence of hypercapnic acidosis from inspired carbon dioxide (ICD) would improve gas exchange in ALI and would be superior to that of low minute ventilation (LVe) produced by reduced respiratory rate, rather than Vt... 
Positive end-expiratory pressure alters the severity and spatial heterogeneity of ventilator-induced lung injury: an argument for cyclical airway collapseScott E Sinclair
Department of Medicine, University of Tennessee, TN, USA
J Crit Care 24:206-11. 2009..We hypothesized that mechanical ventilation in the absence of positive end-expiratory pressure (PEEP) causes VILI to be more severe and regionally variable as compared with PEEP = 8 cm H(2)O...- Deletion of apoptosis signal-regulating kinase-1 prevents ventilator-induced lung injury in micePatrudu S Makena
Department of Medicine, University of Tennessee Health Science Center, Memphis, USA
Am J Respir Cell Mol Biol 46:461-9. 2012..ASK-1 is an important regulator of lung injury and apoptosis in this model. Further study is needed to determine the mechanism of lung injury and apoptosis by ASK-1 and its downstream mediators in the lung... - CXCR4 regulates migration of lung alveolar epithelial cells through activation of Rac1 and matrix metalloproteinase-2Manik C Ghosh
Department of Physiology, Univ of Tennessee Health Science Center, Memphis, TN 38163, USA
Am J Physiol Lung Cell Mol Physiol 302:L846-56. 2012..Similar results were obtained with shRNA knockdown of CXCR4. These findings may help identify a therapeutic target for augmenting epithelial repair following acute lung injury... - Lung injury caused by high tidal volume mechanical ventilation and hyperoxia is dependent on oxidant-mediated c-Jun NH2-terminal kinase activationPatrudu S Makena
Dept of Medicine, Univ of Tennessee Health Science Center, Memphis, TN 38163, USA
J Appl Physiol 111:1467-76. 2011..NAC protects lung injury and apoptosis by inhibiting ROS-mediated activation of JNK and downstream proapoptotic signaling... - Hypercapnic acidosis is protective in an in vivo model of ventilator-induced lung injuryScott E Sinclair
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Washington, BB 1253 HSB Box 356522, Seattle, WA 98195 6522, USA
Am J Respir Crit Care Med 166:403-8. 2002..18 x 10(5) versus 2.84 x 10(5) +/- 0.28 x 10(5) nucleated cells/ml; p = 0.021), and injury score (7.0 +/- 3.3 versus 0.7 +/- 0.9; p < 0.0001). We conclude that hypercapnic acidosis is protective against VILI in this model... - Spatial distribution of sequential ventilation during mechanical ventilation of the uninjured lung: an argument for cyclical airway collapse and expansionScott E Sinclair
Department of Medicine, University of Tennessee Health Sciences Center, 956 Court Ave E222, Memphis, TN 38163 USA
BMC Pulm Med 10:25. 2010..This regional injury heterogeneity was abolished by the application of PEEP = 8 cm H2O. We hypothesized that the spatial distribution of lung injury correlates with areas in which cyclical airway collapse and recruitment occurs... - Preexposure to hyperoxia causes increased lung injury and epithelial apoptosis in mice ventilated with high tidal volumesPatrudu S Makena
Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
Am J Physiol Lung Cell Mol Physiol 299:L711-9. 2010..Immunohistochemistry and in vitro stretch studies showed caspase cleavage in alveolar epithelial cells. In conclusion, preexposure to HO followed by HV produced severe lung injury associated with alveolar epithelial cell apoptosis... 
Prolonged glucocorticoid treatment and secondary prevention in acute respiratory distress syndromeG Umberto Meduri
Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Tennessee Health Science Center and Memphis Veterans Affairs Medical Center 111, 1030 Jefferson Avenue, Suite Room CW444, Memphis, TN 38104, USA
Expert Rev Respir Med 4:201-10. 2010....- Regulation and function of the two-pore-domain (K2P) potassium channel Trek-1 in alveolar epithelial cellsAndreas Schwingshackl
Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee 38111, USA
Am J Physiol Lung Cell Mol Physiol 302:L93-L102. 2012.... - Hyperoxia in the intensive care unit: why more is not always betterWilliam A Altemeier
Department of Medicine, University of Washington, Seattle, Washington 98195 6522, USA
Curr Opin Crit Care 13:73-8. 2007..This review identifies relevant new findings regarding hyperoxic lung injury in the context of providing guidance for future clinical studies... - Airway strain during mechanical ventilation in an intact animal modelScott E Sinclair
Department of Physiology, University of Tennessee Health Science Center, 894 Union Avenue, Nash 426, Memphis, TN 38163, USA
Am J Respir Crit Care Med 176:786-94. 2007..Little direct evidence exists regarding the deformation of airways in vivo during mechanical ventilation, or in the presence of positive end-expiratory pressure (PEEP)... - High tidal volume mechanical ventilation with hyperoxia alters alveolar type II cell adhesionLeena P Desai
Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
Am J Physiol Lung Cell Mol Physiol 293:L769-78. 2007..Mechanical ventilation with hyperoxia promotes changes in focal adhesion proteins and RhoA in AT2 cells that may be deleterious for cell adhesion and migration... - Balance of life and death in alveolar epithelial type II cells: proliferation, apoptosis, and the effects of cyclic stretch on wound healingLynn M Crosby
Department of Physiology, University of Tennessee Health Science Center, Memphis, USA
Am J Physiol Lung Cell Mol Physiol 301:L536-46. 2011..Our results suggest that CS alters several mechanisms of epithelial repair and that an imbalance occurs between cell death and proliferation that must be overcome to restore the epithelial barrier... - Activation and regulation of systemic inflammation in ARDS: rationale for prolonged glucocorticoid therapyG Umberto Meduri
Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Chest 136:1631-43. 2009..75; 95% CI, 0.63 to 0.89; p < 0.001; I(2), 43%) and for those treated before day 14 (RR, 0.71; 95% CI, 0.59 to 0.85; p < 0.001; I(2), 40%)... - Cyclic mechanical strain increases reactive oxygen species production in pulmonary epithelial cellsKenneth E Chapman
Department of Biomedical Engineering, Northwestern University, Evanston, Illinois, USA
Am J Physiol Lung Cell Mol Physiol 289:L834-41. 2005..NADPH oxidase activity was increased after 2 h of CMS, contributing to the production of O2-. Increased ROS production in lung epithelial cells in response to elevated stretch may contribute to the onset of VILI...
Research Grants
- Ventilator-Induced Lung Injury:Mechanisms & ConsequencesScott Sinclair; Fiscal Year: 2005..Aim 3A: Document cyclical airway collapse and reopening via changes in regional ventilation distribution. Aim 3B: Validate a method to estimate appropriate PEEP level to prevent cyclical airway collapse. ..