This study will investigate the hypothesis that the hypermetabolic response (HMR) following burn injury is a thermoregulatory response, under central nervous system (CNS) control, to maintain body temperature (TB) in response to increments in the rates of evaporative and radiational heat loss occurring largely through the burn wound, and that changes in catecholamine metabolism represent a secondary response necessary to achieve maximum increase in heat production (Hp).
Specific aims i nclude: 1) establish the essentiality of the CNS thermoregulator in the production and maintenance of the HMR to burn injury, 2) evaluate the role of the adrenal medulla, sympathetic ganglia, and catecholamines as essential mediators of the HMR, 3) explore the possibility of increased thermogenic sensitivity of burned rats to norepinephrine (NE), similar to that seen with cold adaptation, and 4) determine the role of the burn wound in the afferent arc of the HMR. Responses in Hp, TB hypothalamic temperature (Thy), stored heat, partitioned heat loss, urinary excretion rates of NE and epinephrine (E), and plasma concentrations of NE and E will be measured and correlated with combinations of the following experimental interventions: a) lesioning of the preoptic anterior hypothalamus (POAH), b) no POAH lesion but implantation of the POAH with thermodes and sequential displacement of Thy, c) 35% BSA scald burn, d) adrenal demedullation, e) sympathetic blockade, f) intra- venous administration of E or NE, g) cold stress at 22 degrees C, h) early and delayed burn wound excision and closure with allograft or Biobrane. These studies should establish in the rat, the importance of an intact CNS temperature regulator in the production and maintenance of the HMR following burn injury, and quantitate the role of catecholamines and the adrenal medulla as effectors of the HMR. The wound excision and closure studies will demonstrate the effect of early and delayed eliminations of the burn wound on the interrelationship of the neurohormonal and HMR to burn injury. These results could produce a working model for the study and control of energy metabolism in burned man.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM041293-04
Application #
3299390
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1988-12-01
Project End
1993-11-30
Budget Start
1991-12-01
Budget End
1992-11-30
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Arkansas for Medical Sciences
Department
Type
Schools of Medicine
DUNS #
City
Little Rock
State
AR
Country
United States
Zip Code
72205
Caldwell Jr, F T; Graves, D B; Wallace, B H (2000) Polyclonal antibodies to rat interleukin-6 attenuate fever in rats after burn injuries: a preliminary report. J Burn Care Rehabil 21:220-8
Caldwell Jr, F T; Graves, D B; Wallace, B H (1999) Vagotomy modifies but does not eliminate the increase in body temperature following burn injury in rats. Burns 25:295-305
Caldwell Jr, F T; Graves, D B; Wallace, B H (1999) Humoral versus neural pathways for fever production in rats after administration of lipopolysaccharide. J Trauma 47:120-9
Caldwell Jr, F T; Graves, D B; Wallace, B H (1999) The effect of indomethacin on the cytokine cascade and body temperature following burn injury in rats. Burns 25:283-94
Caldwell Jr, F T; Graves, D B; Wallace, B H (1998) Chronic indomethacin administration blocks increased body temperature after burn injury in rats. J Burn Care Rehabil 19:501-11
Caldwell Jr, F T; Graves, D B; Wallace, B H (1998) Calorigenic response of burned rats with adrenal medullectomies to catecholamines. J Burn Care Rehabil 19:106-14
Caldwell, F T; Graves, D B; Wallace, B H (1998) Studies on the mechanism of fever after intravenous administration of endotoxin. J Trauma 44:304-12
Caldwell Jr, F T; Graves, D B; Wallace, B H (1997) Pathogenesis of fever in a rat burn model: the role of cytokines and lipopolysaccharide. J Burn Care Rehabil 18:525-30
Caldwell Jr, F T; Graves, D B; Wallace, B H (1995) Effect of adrenal medullectomy on responses in heat production, plasma catecholamines and body temperature of burned rats to changes in the temperature of the hypothalamus. Burns 21:273-9
Caldwell Jr, F T; Graves, D B; Wallace, B H (1995) Effect of alpha adrenergic blockade on thermoregulation in adrenal demedullated burned rats. Burns 21:280-4

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