Pathogenesis and treatment of electrical injury

More than ten years ago we postulated that mechanism of tissue injury in victims of electrical shock were more than just thermal has widely taught (J.Theor. Biol. 133:223-237, 1988, Plast. Reconstr. Surg. 86(1):1-11; 1990). Electroporation has been demonstrated (J. Burn Care and Rehab. 16(6):581-588, 1995) and efforts are ongoing to evaluate the role of electroconformational denaturation of membrane ion channels (Biophys. J. 67(2): 603-612, 1994). Additional efforts are directed at the factors which determine if electropermeabilized cells spontaneously seal or undergo necrosis. (more information is available on the ETRP WEB page: http://http.bsd.uchicago.edu/~btc/etrp)

Sealing of Permeabilized Cell Membranes with Surfactant Copolymers

Permeabilization of cell membranes is one of the most common causes of tissue injury in humans. The most common cause of this is free radical mediated peroxidation of membrane phospholipids which is the dominant cause of tissue injury after transient oxygen deprivation. Myocardial infarction, many strokes, limb reattachment after a prolonged period and radiation injury are examples. Other common causes of cell membrane damage include electroporation of muscle and nerve in electrical shock or lightning injury; thermal burns, frostbite and a variety of chemical injuries. Our group has worked to develop clinically acceptable strategies to seal permeabilized cell membranes and limit tissue damage after electrical shock, thermal injury and ionizing irradiation. We demonstrated the feasibility of this strategy several years ago (Proc. Natl. Acad. Sci. 89(10):4524-4528, 1992) and since have been working on methods to enhance efficacy. Recent reports from many other labs have corroborated our initial observations.

Biophysical (mechanical and electrical) control of cellular biosynthetic processes and proliferation

Understanding the transductive coupling mechanisms which permit electric field regulation of tissue repair and remodeling had been a long standing interest. Ongoing collaborative studies have focused on effects of low frequency electroquasistatic fields on signal transduction processes in connective tissue cells and examining the field frequency dependence of cellular responses such as reorganization of cytoskeletal proteins (FASEB J. 10:1552-1558; 1996 ) and cell surface glycoproteins (Biophysical J. 64(1):44-57, 1993).

Regulation of Dermal Scar Formation

Control of scar formation is one of the most important aspects of our research. Scar deformities can be very deforming and disabling following trauma and burns. We have developed pharmaceutical strategies to trigger matrix degradation responses in fibroblasts using calcium antagonists (J. Surg. Res. 49(5):463-466, 1990 ) and PKC inhibitors. In addition, we are developing clinically practical methods to regulate skin temperature to maximize the activity of collagenase and other metalloproteases which are very temperature dependent.

Neurobiological basis of the human aesthetic sense

Many philosophers have postulated that beauty has basic biological meaning. People who have experienced major disfigurement of the face secondary to trauma or burns are not usually successful in reintegrating back into the workplace or society at the pre-injury level. Our goal is understand the basic rules of human aesthetics so that rational approaches to surgical reconstruction of damaged faces can be developed and taught.

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