Pulmonary insufficiency remains a leading cause of mortality and morbidity in a burn patient. We have recently described the mechanism and treatment of the early transient lung injury immediately post-burn and during resuscitation. Our purpose now is to define the more severe and more complex lung dysfunction which occurs in the post-resuscitation period now inaccurately attributed solely to sepsis.
Our aims are to determine 1) whether arachidonic acid metabolites and other vasoactive factors are released from burn tissue in the post-resuscitation period, leading to hypoxia and pulmonary hypertension, 2) whether chemotactic factors and activators of neutrophil O2 radical release (chemiluminescence) are also absorbed, leading to lung permeability edema, 3) whether endotoxin in burn tissue accentuates the lung injury through the local production and release of these mediators of inflammation, and 4) the role of excision or manipulation of burn tissue in either correcting or amplifying the injury. The adult sheep with a 15-30% full thickness burn will be monitored for a ten day period. Lung lymph flow will be used to monitor fluid flux and protein permeability. Blood gases and lung compliance will also reflect function. Lung injury will be quantitated with measurements of lung water as well as biochemical alterations in lung tissue, specifically O2 radical-induced lipid peroxidation. Mediator release will be measured in burn lymph and plasma. Our long term objective is to not only obtain new general information on burn-induced lung injury but also to be able to answer specific clinically important questions such as the optimum and worst times to excise burn tissue relative to time post-burn and degree of inflammation or infection. Physiological, immunological and biochemical methods by three established investigators will be used.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM031662-04
Application #
3279860
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1982-07-01
Project End
1989-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
Demling, R H (2000) Oxandrolone, an anabolic steroid, enhances the healing of a cutaneous wound in the rat. Wound Repair Regen 8:97-102
Demling, R; LaLonde, C; Ikegami, K (1996) Fluid resuscitation with deferoxamine hetastarch complex attenuates the lung and systemic response to smoke inhalation. Surgery 119:340-8
Demling, R; Ikegami, K; Lalonde, C (1995) Increased lipid peroxidation and decreased antioxidant activity correspond with death after smoke exposure in the rat. J Burn Care Rehabil 16:104-10
Lalonde, C; Picard, L; Youn, Y K et al. (1995) Increased early postburn fluid requirements and oxygen demands are predictive of the degree of airways injury by smoke inhalation. J Trauma 38:175-84
Demling, R; LaLonde, C; Heron, P (1994) Initial effect of smoke inhalation injury on oxygen consumption (response to positive pressure ventilation). Surgery 115:563-70
Demling, R; Lalonde, C; Picard, L et al. (1994) Changes in lung and systemic oxidant and antioxidant activity after smoke inhalation. Shock 1:101-7
Lalonde, C; Demling, R; Brain, J et al. (1994) Smoke inhalation injury in sheep is caused by the particle phase, not the gas phase. J Appl Physiol 77:15-22
Demling, R; Lalonde, C; Heron, P et al. (1994) Effect of increasing the tidal volume of smoke breaths on smoke-induced lung dysfunction. J Appl Physiol 76:283-90
LaLonde, C; Ikegami, K; Demling, R (1994) Aerosolized deferoxamine prevents lung and systemic injury caused by smoke inhalation. J Appl Physiol 77:2057-64
Lalonde, C; Picard, L; Campbell, C et al. (1994) Lung and systemic oxidant and antioxidant activity after graded smoke exposure in the rat. Circ Shock 42:7-13

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