The ever-increasing clinical use of heat to treat disease and injury has been driven primarily by advances in laser, micro-wave, radio-frequency and similar technologies, not a fundamental understanding of the biothermomechanics. Heat is used, e.g., in cardiology, dermatology, gynecology, oncology, ophthalmology, orthopedics, and urology. Recent uniaxial studies in our lab reveal that whereas increasing temperature hastens the thermal-damage process, increased loading during heating delays it. Fortunately, the potential complexity of this coupling is simplified by our discovery of a 1-0 time-temperature-load equivalency. The same outcome can be achieved via a multitude of different combinations of heating and mechanical loads if the duration of a non-dimensional (scaled) heating time is the same. This scaling is done by dividing the actual heating time by a temperature- and load-dependent characteristic time, which exhibits an Arrhenius behavior. This reveals that loading influences the process via the activation entropy, not energy. No prior clinical trial of a heating device or strategy has accounted for this coupling. Without such information, optimization will remain elusive. Note, therefore, that most tissues and organs are subjected to multiaxial stresses, thus there is a need to quantify the effects of multiaxial stresses on the thermal process as well as the effects of thermal damage on the multiaxial mechani-cal properties. No such data are available. Rather than focusing on a particular clinical protocol, the goal of this work is to assess the biaxial thermomechanics of collagenous membranes. We shall focus on collagen since it is the primary structural protein in the body, and thus it is present in most tissues that are heat-treated clinically and it is responsible for most of the post-heating structural integrity. Achieving our aims will have much broader impact, however. We recently showed that data from the literature on cell death and the denaturation of other proteins exhibit the same characteristic time-temperature equivalency that we discovered via tests on collagen -- we expect the current findings to similarly provide qualitative insight into the multiaxial thermomechanical behavior of many tissues. The possible multiaxial states of stress that can exist in vivo, or that can be induced by clinical interventions, is almost unlimited. We submit that the most prudent approach to developing a multiaxial theory that has broad predictive capabil-ity is to perform a broad series of isothermal biaxial-isotonic and isothermal biaxial-isometric tests. These data will be sufficient to formulate the requisite constitutive relations, which in turn will be evaluated further using data from combined isometric and isotonic test conditions and non-isothermal heatings. These consitutive relations will allow future evaluation of candidate protocols, from which the most promising can be chosen for animal testing I clinical trials. Without a firmer understanding of the effects of multiaxial stress on thermal-damage processes, we will continue to evaluate particular clinical devices and strategies by trial-and-error. There is a need for a firmer scientific understanding.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL068118-02
Application #
6527797
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Lundberg, Martha
Project Start
2001-08-04
Project End
2004-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
2
Fiscal Year
2002
Total Cost
$135,672
Indirect Cost
Name
Texas A&M University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
047006379
City
College Station
State
TX
Country
United States
Zip Code
77845
Wells, Paul B; Yeh, Alvin T; Humphrey, Jay D (2006) Influence of glycerol on the mechanical reversibility and thermal damage susceptibility of collagenous tissues. IEEE Trans Biomed Eng 53:747-53
Wells, P B; Thomsen, S; Jones, M A et al. (2005) Histological evidence for the role of mechanical stress in modulating thermal denaturation of collagen. Biomech Model Mechanobiol 4:201-10
Baek, S; Wells, P B; Rajagopal, K R et al. (2005) Heat-induced changes in the finite strain viscoelastic behavioir of a collaagenous tissue. J Biomech Eng 127:580-6
Wells, P B; Harris, J L; Humphrey, J D (2004) Altered mechanical behavior of epicardium under isothermal biaxial loading. J Biomech Eng 126:492-7
Harris, Jason L; Humphrey, Jay D (2004) Kinetics of thermal damage to a collagenous membrane under biaxial isotonic loading. IEEE Trans Biomed Eng 51:371-9
Harris, J L; Wells, P B; Humphrey, J D (2003) Altered mechanical behavior of epicardium due to isothermal heating under biaxial isotonic loads. J Biomech Eng 125:381-8
Wright, N T; Humphrey, J D (2002) Denaturation of collagen via heating: an irreversible rate process. Annu Rev Biomed Eng 4:109-28