Mortality from sepsis and acute lung injury (ALI) remains unacceptably high despite recent advances in critical care including early goal-directed therapy and lung protective ventilator strategies. The overall goal of this Translational Program Project in Lung Diseases is to discover novel mechanisms and identify innovative molecular targets by which carbon monoxide (CO) gas exerts cytoprotection during sepsis and ALI. In order to achieve this Program Project's goals. Core D, the CO Delivery in Sepsis and ALI Core, will provide the expertise, resources, facilities, and quality control (QC) services for the delivery of CO in a standardized fashion in Projects 1-4. As the CO Delivery Core, we will provide coordinated resources and expertise to the Project investigators for the centralized delivery of CO in cell culture systems, preclinical animal models, and in subjects with sepsis-induced ALI in a Phase I Biosafety Clinical Trial. Specifically, Core D will develop and implement standardized protocols to administer CO and monitor CO concentrations in cell culture systems, animal models of sepsis and ALI, and in mechanically ventilated subjects with sepsis-induced ALI as a central service for Project investigators. A highly innovative feature of this proposal is the development and validation of a CO delivery protocol for critically ill patients requiring mechanical ventilation. Core D will also be responsible for standardizing the animal models of sepsis and ALI employed by investigators in all four Projects. By using the same highly trained and experienced personnel as well as standardized Good Laboratory Practice (GLP)-like protocols, we will ensure that all CO exposures are performed under uniform conditions, that CO exposures are strictly regulated, and that CO levels and animals are properly monitored throughout experiments. In our Phase I Biosafety Clinical Trial, Core D will provide the expertise required to standardize the CO administration protocol, ensure continuous real-time monitoring of CO concentrations in the inspiratory and expiratory gases, and assess carboxyhemoglobin (COHb) levels in subjects to assure high quality safety and monitoring standards. By consolidating and leveraging highly skilled and experienced staff, facilifies, and equipment in Core D and making them available to all Projects, we will greatly reduce the cost of producing high-quality data. This approach will facilitate and promote synergisfic interactions between investigators in the different Projects. Therefore, Core D, the CO Delivery in Sepsis and ALI Core, will play an integral role in the successful completion of the work proposed in this Program Project.
Core D will provide all four Projects with standardized methods, facilities, and personnel for delivery of carbon monoxide (CO) gas to cells in culture, to animals during experiments, and to people as part of a clinical trial. By centralizing these services, Core D will coordinate and facilitate interactions between the investigators of the four different Projects.
| Ma, Kevin C; Schenck, Edward J; Pabon, Maria A et al. (2018) The Role of Danger Signals in the Pathogenesis and Perpetuation of Critical Illness. Am J Respir Crit Care Med 197:300-309 |
| Schenck, Edward J; Oromendia, Clara; Torres, Lisa K et al. (2018) Rapidly Improving ARDS in Therapeutic Randomized Controlled Trials. Chest : |
| Schenck, Edward J; Ma, Kevin C; Murthy, Santosh B et al. (2018) Danger Signals in the ICU. Crit Care Med 46:791-798 |
| Ghanta, Sailaja; Kwon, Min-Young; Rosas, Ivan O et al. (2018) Mesenchymal Stromal Cell Therapy: Does the Source Matter? Crit Care Med 46:343-345 |
| Baron, Rebecca M; Kwon, Min-Young; Castano, Ana P et al. (2018) Frontline Science: Targeted expression of a dominant-negative high mobility group A1 transgene improves outcome in sepsis. J Leukoc Biol 104:677-689 |
| Shu, Chang; Huang, He; Xu, Ying et al. (2018) Pressure Overload in Mice With Haploinsufficiency of Striated Preferentially Expressed Gene Leads to Decompensated Heart Failure. Front Physiol 9:863 |
| Harrington, John S; Schenck, Edward J; Oromendia, Clara et al. (2018) Acute respiratory distress syndrome without identifiable risk factors: A secondary analysis of the ARDS network trials. J Crit Care 47:49-54 |
| Siempos, Ilias I; Ma, Kevin C; Imamura, Mitsuru et al. (2018) RIPK3 mediates pathogenesis of experimental ventilator-induced lung injury. JCI Insight 3: |
| Rosas, Ivan O; Goldberg, Hilary J; Collard, Harold R et al. (2018) A Phase II Clinical Trial of Low-Dose Inhaled Carbon Monoxide in Idiopathic Pulmonary Fibrosis. Chest 153:94-104 |
| Suliman, Hagir B; Kraft, Bryan; Bartz, Raquel et al. (2017) Mitochondrial quality control in alveolar epithelial cells damaged by S. aureus pneumonia in mice. Am J Physiol Lung Cell Mol Physiol 313:L699-L709 |
Showing the most recent 10 out of 85 publications
