Title
Burns - Volume 31, Issue 5 , August 2005, Pages 568-577
Copyright © 2005 Elsevier Ltd and ISBI All rights reserved.
The relative thermal stability of tissue macromolecules and cellular structure in burn injury
F. Despaa, D.P. Orgillb, J. Neuwalderb and R.C. Leea
Department of Surgery, MC6035, The University of Chicago, Chicago,
IL 60637, USA
Department of Surgery, Brigham and Woman's Hospital, Harvard Medical School,
Boston, MA 02115, USA
When tissue is subjected to higher than physiological temperatures, protein
and cell organelle structures can be altered resulting in cell death and
subsequent tissue necrosis. A burn injury can be stratified into three main
zones, coagulation, stasis and edema, which correlate with the extent of
heat exposure and thermal properties of the tissue. While there has been
considerable effort to characterize the time–temperature dependence
of the injury, relatively little attention has been paid to the other important
variable, the thermal susceptibility of the tissue. In the present study,
we employ a standard physical chemistry approach to predict the level of
denaturation at supraphysiological temperatures of 12 vital proteins as
well as RNA, DNA and cell membrane components. Melting temperatures and
unfolding enthalpies of the cellular components are used as input experimental
parameters. This approach allows us to establish a relation between the
level of denaturation of critical cellular components and clinical manifestations
of the burn through the characteristic zones of the injury. Specifically,
we evaluate the degree of molecular alteration for characteristic temperature
profiles at two different depths (Mid-Dermis and Dermis-Fat interface) of
80 °C; 20 s contact burn. The results of this investigation suggest
that the thermal alteration of the plasma membrane is likely the most significant
cause of the tissue necrosis. The lipid bilayer and membrane-bound ATPases
show a high probability of thermal damage (almost 100% for the former and
85% for the latter) for short heat exposure times. These results suggest
that strategies to minimize the damage in a burn injury might focus on the
stabilization of the cellular membrane and membrane-bound ATPases. Further
work will be required to validate these predictions in an in vivo model.