High-energy electrical trauma remains a major cause of occupational injury and disability. Nonetheless, major advances in therapy have been slow to develop because of the unresolved questions regarding its pathophysiology. We have shown in laboratory studies that the biophysical mechanisms of tissue injury are more complex than previously thought, that is, both thermal and direct electrical mechanisms are likely to be involved, and their relative contribution is highly dependent on the duration of electrical current passage. Skeletal muscle and nerve cells are the most vulnerable to direct electrical mechanisms of cellular membrane damage (electroporation and electroconformational protein denaturation). Our subsequent reports indicate that it may by possible to restore viability to tissues injured by direct electrical mechanisms using biocompatible surfactants, whereas thermally injured (burned) tissue requires surgical excision. One essential need addressed in this project is to determine the relative contribution of thermal versus electrical mechanisms of tissue injury over a range of exposures characteristic of occupational electrical trauma. The proposed project would accomplish this by separately exposing tissue to the equivalent thermal and electrical stresses involved in a 60 Hz electrical trauma. A second essential need is to develop an imaging method for electrical injury diagnosis. We propose to refine magnetic resonance imaging (MRI) analysis sequences, useable on common hospital MRI machines, which can distinguish heat-damaged from pure electrical-damaged tissue on the basis of extent of tissue protein denaturation. Such a diagnostic tool would be of tremendous clinical value because rapid detection, discrimination and localization of tissue injury would accelerate and guide clinical management. Although essential for optimal electrical injury management, these methods would also be of practical clinical value for assessment of new medical therapies as well as valuable for pure thermal (hot and cold) injury evaluation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM061101-04
Application #
6611356
Study Section
Special Emphasis Panel (ZRG1-SSS-X (18))
Program Officer
Somers, Scott D
Project Start
2000-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2005-06-30
Support Year
4
Fiscal Year
2003
Total Cost
$280,854
Indirect Cost
Name
University of Chicago
Department
Surgery
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
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Mustafi, Devkumar; Smith, Catherine M; Makinen, Marvin W et al. (2008) Multi-block poloxamer surfactants suppress aggregation of denatured proteins. Biochim Biophys Acta 1780:7-15
Collins, John M; Despa, Florin; Lee, Raphael C (2007) Structural and functional recovery of electropermeabilized skeletal muscle in-vivo after treatment with surfactant poloxamer 188. Biochim Biophys Acta 1768:1238-46
Chen, Wei; Zhongsheng, Zhang; Lee, Raphael C (2006) Supramembrane potential-induced electroconformational changes in sodium channel proteins: a potential mechanism involved in electric injury. Burns 32:52-9
Matthews 2nd, Kenneth L; Aarsvold, John N; Mintzer, Robert A et al. (2006) Tc-99m pyrophosphate imaging of poloxamer-treated electroporated skeletal muscle in an in vivo rat model. Burns 32:755-64
Despa, F; Orgill, D P; Neuwalder, J et al. (2005) The relative thermal stability of tissue macromolecules and cellular structure in burn injury. Burns 31:568-77
Bier, Martin; Chen, Wei; Bodnar, Elena et al. (2005) Biophysical injury mechanisms associated with lightning injury. NeuroRehabilitation 20:53-62
Gissel, Hanne; Despa, Florin; Collins, John et al. (2005) Magnetic resonance imaging of changes in muscle tissues after membrane trauma. Ann N Y Acad Sci 1066:272-85
Lee, Raphael C (2005) Cell injury by electric forces. Ann N Y Acad Sci 1066:85-91

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