The acute respiratory distress syndrome (ARDS) is a serious clinical problem. It occurs as a sequelae to other serious illnesses, often multiple traumas. ARDS is difficult to study in human patients because of the variability of patient populations. Multiple traumas are difficult to model in animal preparations because of variability of injury and humane considerations since most forms of trauma are associated with pain. ARDS is not commonly seen in people with burn injury alone, but some 20% of patients who sustain thermal trauma develop ARDS, usually as a result of inhalation of smoke. This research summary points out the complexity of the problems related to ARDS especially that form of the syn-drome associated with burn injury and smoke inhalation. It also illustrates the contribution to that knowledge that has been made by co-investigators of this proposal. Given the successful collaboration of our group, the unique models, facilities and techniques that we have developed together, our goals and objectives should be accomplished in this proposal. In addition to the understanding of the cascade of events that comprise the development of ARDS, the proposal should also test efficacy of several therapeutic interventions and when they would be effective in clinically relevant models. Although we do not describe any human studies in our proposal, many of the co-investigators are prominent clinicians actively involved in daily clinical care of burned patients at two of the major burn units in the world. Consequently, the findings of our proposal can be rapidly tested in patient populations. Finally, given the present interactions of this group of investigators, the laboratory and clinical environment in which they work, pathophysiological interactions and therapeutic interventions that were not described in the proposal are very likely to develop during the duration of the proposal.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM066312-03
Application #
7105455
Study Section
Special Emphasis Panel (ZGM1-TB-6 (04))
Program Officer
Somers, Scott D
Project Start
2004-08-01
Project End
2009-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
3
Fiscal Year
2006
Total Cost
$1,440,353
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555
Hamahata, Atsumori; Enkhbaatar, Perenlei; Lange, Matthias et al. (2012) Administration of poly(ADP-ribose) polymerase inhibitor into bronchial artery attenuates pulmonary pathophysiology after smoke inhalation and burn in an ovine model. Burns 38:1210-5
Yamamoto, Yusuke; Sousse, Linda E; Enkhbaatar, Perenlei et al. (2012) ?-tocopherol nebulization decreases oxidative stress, arginase activity, and collagen deposition after burn and smoke inhalation in the ovine model. Shock 38:671-6
Maybauer, Marc O; Maybauer, Dirk M; Fraser, John F et al. (2012) Combined recombinant human activated protein C and ceftazidime prevent the onset of acute respiratory distress syndrome in severe sepsis. Shock 37:170-6
Yamamoto, Yusuke; Enkhbaatar, Perenlei; Sousse, Linda E et al. (2012) Nebulization with ?-tocopherol ameliorates acute lung injury after burn and smoke inhalation in the ovine model. Shock 37:408-14
Lange, Matthias; Hamahata, Atsumori; Traber, Daniel L et al. (2012) Pulmonary microvascular hyperpermeability and expression of vascular endothelial growth factor in smoke inhalation- and pneumonia-induced acute lung injury. Burns 38:1072-8
Yamamoto, Yusuke; Enkhbaatar, Perenlei; Sakurai, Hiroyuki et al. (2012) Development of a long-term ovine model of cutaneous burn and smoke inhalation injury and the effects of early excision and skin autografting. Burns 38:908-16
Hamahata, Atsumori; Enkhbaatar, Perenlei; Lange, Matthias et al. (2012) Administration of a peroxynitrite decomposition catalyst into the bronchial artery attenuates pulmonary dysfunction after smoke inhalation and burn injury in sheep. Shock 38:543-8
Rehberg, Sebastian; Yamamoto, Yusuke; Sousse, Linda et al. (2012) Selective V(1a) agonism attenuates vascular dysfunction and fluid accumulation in ovine severe sepsis. Am J Physiol Heart Circ Physiol 303:H1245-54
Lange, Matthias; Hamahata, Atsumori; Traber, Daniel L et al. (2011) Preclinical evaluation of epinephrine nebulization to reduce airway hyperemia and improve oxygenation after smoke inhalation injury. Crit Care Med 39:718-24
Sousse, Linda E; Yamamoto, Yusuke; Enkhbaatar, Perenlei et al. (2011) Acute lung injury-induced collagen deposition is associated with elevated asymmetric dimethylarginine and arginase activity. Shock 35:282-8

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