ELECTRICAL SHOCK TRAUMA

Colin McFaul, PhD, Mei Li, MD, Ze Liang, and Raphael C. Lee, MD, ScD

Chicago Electrical Trauma Research Institute

Shanghai Power Hospital

Peking Union Medical College

Pritzker School of Medicine, The University of Chicago,

Chicago, Illinois 60637, U.S.A.

KEY WORDS: electrical injury, burn, membrane, electroporation, denaturation, tissue

Shortened Title: Electrical Injury

Send Proofs to: Raphael C. Lee, M.D., Sc.D.Department of Surgery, MC 6035The University of Chicago5841 South Maryland AvenueChicago, IL 60637Phone: (773) 702-6302 Fax: (773) 702-0661e-mail: rlee@surgery.bsd.uchicago.edu

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Contents

Contents 2

Introduction 4

Electrical Transport within Tissues 6

Physicochemistry of Tissue Injury 9

Low Frequency Electric Shocks 9

Direct Electric Force Damage. 10

Thermal “Burn” Injury 17

Electro-conformational Denaturation of Transmembrane Proteins 20

Radiofrequency (RF) and Microwave Burns 22

Lightning Injury 23

Common Clinical Syndromes Following Electrical Injury 24

Diagnostic Imaging of Electrical Injury 25

Summary and Conclusions 27

Acknowledgements 28

References 29

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Introduction

The development of electrical power has been one of the most impactful engineering feats of

modern humanity. As electric power penetrates further into society, it poses greater risk to

human society in terms of safety. Many citizens have experienced electric shock at least once in

their lifetime. The pain and fear generated from encounters with electricity usually prevents us

from further tampering with such a dangerous force. However, no matter how careful, accidents

can and do occur, especially among electrical workers who handle commercial electrical power

lines every day. Recently, use of electrical power in non-lethal weapons carried by law

enforcement has made it into the mainstream in some countries. The purpose of this chapter is to

provide a basic overview of the harmful effects of electrical force from both the engineering and

medical perspectives.

The range of clinical manifestations of electrical shock is not well documented. Many survivors

of accidental electrical shock never seek medical attention. The data that exists is from those who

do seek attention or from a few case studies of electrical workers. Furthermore, there is

considerable variation in how electrical injury and safety is managed across various countries. In

industrializing countries safety practices are often not the top priority, resulting in high rates of

injury. A study of burn injuries by Nursal et al. during a one-year (2000-2001) period indicated

that 21% of burn patients were victims of electrical injury (1). In highly industrialized nations,

electrical shock rates are on the decline. In the United States, electrocution remains the fifth

leading cause of fatal occupational injury with an estimated economic impact of more than 1

billion dollars annually (2). The rates of injury are highest among electrical workers, mostly

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caused by ‘live’ electrical equipment, such as wiring, light fixtures, and overhead power lines

(3). A study in Virginia suggested that public utilities have the highest rate of fatal electrical

injuries among all industrial sectors. More than 90% of these injuries occur in men, mostly

between the ages of 20 and 34, with 4 to 8 years of experience on the job (4). Another study

found that the average age of victims was 37.5 years and the average experience was 11.3 years.

In yet another study, the incidence in a 9-year period was 8.3%, 96% of victims were male, and

the mean age was 32.7 years (5). For survivors, the injury pattern is very complex, with a high

disability rate due to accompanying neurologic damages and/or loss of limbs.

Away from the workplace, most electrical injuries are due to either indoor household low-

voltage (<1000 V) electrical contact or outdoor lightning strikes (6). An etiology study

conducted in India reveals that 60% of high-voltage electric burns were due to exposed electric

wires on farm or agricultural land, while low-voltage electric shocks happened mainly at home

(47%) and at professional utility places (29%) (3). Domestic household 60 Hz electrical shocks

are common and usually result in minor peripheral neurological symptoms or occasionally skin

surface burns. However, more complex injuries may result depending on the current path,

particularly following oral contact with household appliance cord disclosures or outlets by small

children (6). Compared to a high-voltage shock that is usually mediated by an arc, low-voltage

shocks are more likely to produce a prolonged, “no-let-go” contact with the power source. This

“no-let-go” phenomenon is caused by an involuntary, current-induced, muscle spasm (7). For

60 Hz electrical current, the “no-let-go” threshold for axial current passage through the forearm

is 16 mA for males and 11 mA for females (7,8).

There are roughly 30 human deaths annually in the United States due to lightning strikes and

approximately ten times that number of injuries (9,10). The range of lightning injury extent is

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quite broad, depending upon the magnitude of exposure and the condition of the victim. Usually

lightning hits result in surface burns, complex neurological damage similar to blunt head trauma,

peripheral neurologic injury, and cardiac damage (11). Radiofrequency and microwave injuries

are less common. Nonetheless, they represent an important medical problem to understand. At

higher frequencies, when the wavelength is short enough to couple at the atomic level, the fields

can be ionizing as well as can cause molecular heating. Electrical trauma may produce such

complex patterns of injury because of variations in the source of the electricity, differences in

tissue-current interactions by electrical frequency, the variation in current density along its

pathway through the body, and variations in body size, body position and use of protective gear.

No two cases are the same.

Electrical Transport within Tissues

The fundamental bioengineering perspective is that the human body is considered to be a

compartmentalized (or lumped element) conducting dielectric. It consists of about 60% water by

weight: 33% intracellular and 27% extracellular (12). Body fluid in both the intracellular and

extracellular compartments is highly electrolytic, and these two compartments are separated by a

relatively impermeable, highly resistive plasma membrane. Current within the body is carried by

mobile ions in the body fluid. The concentration of mobile ions results in a conductivity of

approximately 1.4 S m-1 in physiological saline. While electrons are the charge carriers in

metallic conductors or electrical arcs, in the human body the charge carriers are ions. The

conversion from one to the other occurs at the skin surface through electrochemical reactions

(13).

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At low frequencies (i.e., below radio frequencies), the electric current passing across the body

distributes such that the electric field strength is nearly uniform throughout any plane

perpendicular to the current path (14–16). As a consequence, the current density distribution

depends on the relative electrical conductivity of various tissues and the frequency of the current.

Experimental data support this basic concept. Sances et al. measured the current distribution in

the hind limb of anesthetized hogs (16). They found that major arteries and nerves experienced

the largest current density because of their higher conductivity. It was also observed that skeletal

muscles carried the majority of the current due to their predominant volumetric proportions.

At a macroscopic scale, upper limbs are mostly involved in electric shocks, especially the right

upper limb, as would be expected from dominant hand interactions with electrical sources (17).

Cela et al. modeled this using a multiresolution admittance method. In this method, a human arm

was initially split into uniformly-sized voxels. Within regions of uniform composition, voxels

were combined, greatly reducing the number of voxels in the model. Fine resolution was

maintained at material boundaries (18). The voxels were then connected as a network of

conductors, allowing the calculation of current density at each voxel. This model was applied to

predict the damage in skeletal muscle caused by cell lysis, and to simulate the injury pattern. The

simulation found that current density increases towards the distal part of the arm as the cross

sectional area decreases. The wrist has particularly high current density and damage due to the

constriction and the high fraction of less conductive bone. The overall impedance of this arm

model is 599 Ω, which is consistent with the estimated resistance of the human body (18).

Computational models of human high-voltage electrical shock suggest that the induced tissue

electric field strength in the extremities is high enough to electroporate skeletal muscle and

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peripheral nerve cell membranes (19–22) and to possibly cause electroconformational

denaturation of membrane proteins.

At a more microscopic scale, low frequency current distribution within tissue is determined by

the density, shape and size of cells. The cell membrane acts as an insulating ion transport barrier

that mostly shields the cytoplasmic fluid from low frequency electrical current. In addition, the

presence of cells diminishes the area available for ionic current and, in effect, makes tissues less

conductive. As cell size increases, the membrane has less impact on a cell’s electrical properties,

because the volume fraction of the cell occupied by the membrane is inversely proportional to

the total cell radius (23). Similarly, the conductivity of skeletal muscle parallel to the long axis of

the muscle cells is greater than that perpendicular to this axis. Solid volume fraction of the

extracellular matrix can also be important in certain tissues and anatomic locations. For example,

the resistivity of cortical bone and epidermis is higher than other tissues because their free water

content is lower, as evidenced in the recent work by Kalkan et al. (24).

At higher frequencies, in RF and microwave ranges, the current distribution is dependent on

different parameters. The cell membrane is no longer an effective barrier to current passage, and

capacitive coupling of power across the membrane readily permits current passage into the

cytoplasm. Frequency-dependent factors like energy absorption and skin-depth effects govern

the field distribution in tissues. At the highest frequency ranges, including light and shorter

wavelengths, other effects such as scattering and quantum absorption effects become important

in governing field distribution in tissues. Table 1 provides a categorization of frequency regimes,

with the corresponding wavelength spectrum, their common applications, and their effects on

tissues as a result of electrical injury. Mechanisms of biological effects are different in each

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regime. A discussion of injury mechanisms must also be separated according to the frequency

regime.

Table 1 Frequency - wavelength regimes with general applications and harmful effects

Field Frequency(cycles/sec)

Energy Coupling Mechanism

Tissue Damage

D.C. to 103 Ionic Currents Forces on Cell Structures

Joule Heating Membrane Poration

103 to 107 Ionic Currents Field Energy Absorption by

cells

Joule Heating Cell spinning

107 to 109 Field Energy Absorption by proteins

Macromolecular Heating

109 to 1011 Field energy absorption by water

Microwave Heating of water

1011 to 1015 Field Energy Absorption by atomic bonds

Photo-optical protein damage

Physicochemistry of Tissue Injury

Low Frequency Electric Shocks

The biophysical mechanism of injuries caused by contacting electrical power sources remain

controversial (5). It has been shown that the pathophysiology of tissue electrical injury is

complex, involving thermal, electroporation, and electrochemical interactions (24–27), and blunt

mechanical trauma secondary to thermoacoustic blast from high-energy arc (28). The various

modes of trauma lead to complex patterns of injury which remain incompletely described.

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Different conductivities in different tissues causes tissue damages to vary from swelling to full-

thickness burns in electric shock. According to Ohm’s law, tissue damage in electric shock

shows typical patterns in which tissues with higher conductivity presenting more severe clinical

outcomes. Nerves, blood, mucous membranes, and muscles or moist hands possess the lowest

resistance in the human body. Thus the appearance may not reflect the situations of patients

properly; internal injuries can be severe, even when skin burns seem moderate. It is worth

mentioning one unique complication of electric shock: rhythmic disturbances of the heart.

Cardiac muscles are specialized smooth muscles that contract constantly. This synchronization of

muscle movement is governed by the sinus node, a group of cells within the heart that

spontaneously produce electrical impulses. A current of more than 50–100 mA can disturb these

impulses and develop ventricular fibrillation.

The understanding of electric injuries has deepened from simple burns by Joule heating to

complicated models of cell damages. These new concepts are helping physicians with better

management of electrical injury patients (29). In the most general terms, tissue damage exists

when proteins and other biomolecules, cellular organelle membranes or water content is altered.

Among all the components of the cells and tissues which can be damaged by an electrical shock,

it is the thin cell membrane which has the greatest vulnerability. Thus, the cell membrane

appears to be most important determinate of tissue injury accumulation.

The most important function of the cell membrane is to provide a diffusion barrier against free

ion diffusion (30). Because most metabolic energy of mammalian cells is used in maintaining

transmembrane ionic concentration differences (31), the importance of the structural integrity of

the lipid bilayer is apparent. The conductance of electropermeabilized membranes may increase

by several orders of magnitude. ATP production and in turn, ATP-fueled protein ionic pumps,

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cannot keep pace, leading to metabolic energy exhaustion. Cell necrosis results if the membrane

is not sealed. Thus, in discussing tissue injury resulting from electrical shock, the principal focus

is directed at kinetics of cell membrane injury and the reversibility of that process. A simulation

study of membranes by Tarek (32) explains the electroporation phenomena in bilayers.

Direct Electric Force Damage.A cell within an applied DC or low-frequency electric field will experience electric forces which

will act most forcefully across and along the surface of the cell membrane. The forces acting

across the membrane can alter membrane protein conformation and disrupt the structural

integrity of the lipid bilayer. The magnitude of the forces acting across the membrane is related

to the induced transmembrane potential Vm. Vm depends on a variety of factors, such as the intra-

and extracellular medium conductivity, cell shape and size, the external electric field strength E

as well as how the electric field vector orients with respect to the point of interest on the cell

membrane (22–24).

Given that most cells are either somewhat spheroidal or cylindrical in shape, the relationship

between the externally applied electric field and the induced transmembrane potential can be

simplified to either of two simple forms. Under physiologic tissue conditions, the peak

magnitude of induced transmembrane potential Vm (VPm) at the electrode-facing poles of spherical

cells can be expressed as:

V pm = 1.5 Rcell cos (· (1+(f / fs)2)-1/2 · Epeak, (1)

Where Rcell is the radius of the cell, Epeak is the peak field strength in the tissue surrounding the

cell, is the angle off axis from the field direction, fs is the sub--dispersion frequency limit

below which the cell charging time is short compared to rate of field change, and f is the field

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frequency (23). For cylindrical shaped cells, such as skeletal muscle and nerve cells, aligned in

the direction of the field (herein assigned the z coordinate), the induced transmembrane potential

takes a different form. Under these circumstances an electrical space constant parameter

becomes useful in describing the electrical properties of the cell. The induced transmembrane

potential can be expressed as a function of z:

Vpm (z)  A m sinh (z / m) (1+(f / fs)2)-1/2 Epeak (2)

Where m is the electrical space constant of the cell, A is a variable that depends on cell length,

the position z = 0 corresponds to the mid-point of the cell (34). The bottom of Figure 1 illustrates

schematically the spatial variation of Vpm (z) on the cell size for both of these cases. Of course,

physically larger cells like skeletal muscle and peripheral nerve oriented in the direction of the

electrical field would experience an induced transmembrane potential of greater magnitude than

smaller cells.

Under normal physiological conditions, the cell’s outer plasma membrane is an electrical

transport barrier, restricting current passage through the cell. That leads to an induced

transmembrane potential (23). Thus larger cells are more vulnerable to membrane disruption by

electrical shock current.

Equations (1) and (2) are valid as long as the electrical properties of the cell membrane remain

constant. The natural transmembrane potential of mammalian cells has a magnitude of less than

100 mV (36). When an extracellular imposed electric field results in an induced transmembrane

potential difference magnitude of greater than 200-300 mV across a mammalian cell membrane,

molecular alterations occur that can lead to membrane disruption with subsequent loss of

membrane transport barrier function (23). Gaylor et al. also showed that crowding of cells

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increases the induced transmembrane potential by preventing the electric field lines from

diverting around a given cell. One effect of this is that cells in the interior of a muscle are more

susceptible to direct damage from an applied electric field than are cells that are adjacent to more

conductive tissue.

Figure 1. Top: Dependence of the induced transmembrane potential difference on cell size and

position when cells are exposed to the same electric field. Electrical current lines are the same as

electric field lines (shown as stream lines with arrows). Constant voltage lines are shown in

darker color without arrows. Bottom: the transmembrane potential difference as a function of

position along the direction of the applied electric field. The longer cell has a much larger

transmembrane potential at its ends than the shorter cell.

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The principal mechanisms of damage are electroporation of the lipid bilayer and electro-

conformational denaturation of the membrane proteins. Electro-conformational damage to

membrane proteins has been well documented for voltage-gated membrane protein channels

(37,38). The processes occur quickly, on the order of milliseconds, after strong fields are applied.

Electroporation is the biophysical process of cell membrane disruption resulting from an

electrical field in the plasma membrane of such magnitude that re-ordering of lipids in the lipid

bilayer takes place (33,37,38). Investigation of electroporation of many cells within a tissue was

initially driven by the need for a better understanding of the pathophysiology of electrical injury

(39–41). In the early 90’s, it was studied in connection with cardiac defibrillation shocks (42,43).

More recently, tissue electroporation has begun to be envisioned as a potential therapeutic tool in

the medical field. It has found useful applications at both the single and multicellular level in 1)

enhanced cancer tumor chemotherapy (electrochemotherapy, (44,45); 2) localized gene therapy

((46,47); 3) transdermal drug delivery and body fluid sampling (48–50); 4) introduction of

foreign DNA into cells; 5) introduction of enzymes, antibodies, viruses, and other agents or

particles for intracellular assays; 6) cell fusion; 7) to insert or embed macromolecules into the

cell membrane; 8) to sample microenvironments across membranes (51); 9) gene delivery in

human embryonic stem cells (52), gene transfer in whole embryos (53) and gene repair in

mammalian cells (54). Recent reviews and books published have extensively treated this subject

(33–35,50,55–58).

The process of cell membrane electroporation can be simulated as a chemical reaction that

involves the rearrangement of phospholipids in the bilayer portion of the cell membrane. Bier et

al. constructed a thermodynamic model of this process. It is driven by energy differences of the

minimum energy state in pore formation and the bilayer state equaling the line tension minus the

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Kelvin Polarization stresses within the defect. This leads to an estimate of pore radius of

0.36 nm, consistent with previous reports (59).

Whether cells survive electroporation depends on whether the defects are transient or stable.

Stability of defects is governed by the magnitude of the imposed transmembrane potential, the

duration for which it is imposed, membrane composition and the membrane temperature. The

time required to electroporate a cell is also dependent on these same variables and typically

ranges from tens of microseconds to milliseconds. After application of a brief electroporating

field pulse, the transiently electroporated membrane will spontaneously seal. Sealing follows

removal of water from the membrane defects. Sealing kinetics are often orders of magnitude

slower than the field relaxation because the forces driving the molecular sealing events are not as

strong as those caused by the electroporating electric field. Sealing of electropores requires

reordering of membrane lipids and removal of water molecules from the pore, both time and

energy consuming processes (44–46).

The threshold transmembrane potential for induction of membrane electroporation is remarkably

similar across cell types. The threshold Vm for electroporation has been found to be in the range

300-350 mV (60–63). Several authors have developed models to explain the experimentally

observed values of Vm required for electroporation and associated transmembrane aqueous

dynamics (40,64). Using empirical data as parameters in an asymptotic approximation (39), the

threshold Vm is predicted to be approximately 250 mV, consistent with reported experimental

data.

Generally, for most media-suspended, isolated cells with a typical diameter of 10 - 20 µm, the

DC field strength threshold for electroporation is in the range of 1 kV cm-1. By comparison, the

fields required to alter large cells are much less. Due to their relatively long length, skeletal

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muscle cells, up to 8 cm long in large animals, and nerve cells, up to 2 m long, have much lower

electroporation thresholds. Therefore, muscle and nerve cell membranes are likely to be damaged

with electrical fields as small as 60 V cm-1.

The distribution of electropore formation in a cell placed in an applied field was addressed by

DeBruin and Krassowska (65,66). Expanding from previous theoretical models, and including

the fact that the membrane charging time of about 1 µs is very short compared to a 1 ms field

duration, they concluded that supraphysiological Vm at the pole caps is large enough to create

pores, and thereby effectively prevent a further increase in Vm in these areas. This confirms early

experimental findings which show a saturation of Vm that is independent of the field strength for

high-voltage shocks (52–54). After the effect of ionic concentrations is included, DeBruin and

Krassowska’s model is able to confirm asymmetries in Vm observed in respect to the

hyperpolarized (anode-facing) and hypopolarized (cathode-facing) pole of a cell (61,62,70).

Although the pore sealing time in the range of seconds predicted by the model is in agreement

with some published experimental results (71), others have found longer sealing times in the

range of several minutes (60,61,72). This might be explained by the fact that: 1) this model is

based on pure lipid bilayers instead of cell membranes embedded with proteins, and 2) it only

considers primary pores formed by Vm during the shock and not the secondary pores formed after

the external field pulse ends, that provide transport routes for macromolecules.

Bhatt et al measured electroporation damage accumulation using isolated, cooled in vitro rat

biceps femoris muscles (25). After the initial impedance measurement, an electric field pulse was

delivered to the muscle creating tissue field pulse amplitudes ranging between 30-120 V cm-1, in

the range of typical forearm field strengths in high-voltage electrical shock. The duration of the

DC pulses ranged from 0.5-10 ms. These short pulses reduce Joule heating to insignificant

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levels. Field pulses were separated by 10 s to allow thermal relaxation. The drop in the low

frequency electrical impedance in the muscle tissue following the application of short-duration

DC pulses indicated skeletal muscle membrane damage. A decrease in muscle impedance

magnitude occurs following DC electric field pulses that exceed 60 V cm-1 magnitude and 1 ms

duration. These results indicate that the field strength, pulse duration, and number of pulses are

all factors that determine the extent of electroporation damage.

Based on these results, Block et al. (27) electrically shocked fully anesthetized female Sprague-

Dawley rats through cuff-type electrodes wrapped around the base of the tail and one ankle using

a current-regulated DC power supply. The objective was to determine whether electroporation of

skeletal muscle tissue in-situ could lead to substantial necrosis. The study involved

histopathological analysis and diagnostic imaging of an anesthetized animal hind limb. A series

of 4 ms DC-current pulses, each separated by 10 s to allow complete thermal relaxation back to

baseline temperature before the next field pulse, was applied. The electric field strength

produced in the thigh muscle was estimated to range from 37-150 V cm-1, corresponding to

applied currents ranging from 0.5 – 2 A. These tissue fields were suggested to be on the same

level as that experienced by many victims of high-voltage electrical shock. Muscle biopsies were

obtained from the injured as well as the collateral control legs six hours post shock, and

subjected to histopathological analysis. Sections of electrically shocked muscle revealed

extensive vacuolization and hypercontraction-induced degeneration band patterns which were

not found in un-shocked contra-lateral controls (Figure 2 of (27)). The fraction of

hypercontracted muscle cells increased with the number of applied pulses. These results are

consistent with the investigators’ hypothesis that non-thermal electrical effects alone can induce

cellular necrosis. The pathologic appearance of the shocked muscle was similar to that seen in

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malignant hyperthermia, indicating that electroporation may lead to Ca2+-influx into the

sarcoplasm. A similar muscle injury pattern has been described in a human electrical injury

victim published by deBono in a clinical case report (73). These results suggested that direct

electrical injury of skeletal muscle in-situ can lead to the commonly seen pattern of injury in

electrical shock victims even in the absence of pathologically significant Joule heating.

Thermal “Burn” Injury Passage of electrical current through electrically conducting media leads to Joule heating that can

lead to severe burn injury in electrical shock victims. Burn injury is used here to specifically

refer to tissue injury by damaging supraphysiological temperatures. Burn effects are related to

lysis of cell membranes and protein denaturation often followed by recognizable changes in the

optical properties of tissue. There are two different potential outcomes for the denatured protein,

which depend on the initial molecular structure and configuration. The first occurs when the

native folded conformational state of the protein, held by intra-molecular bonds, is different from

the most favored conformation without intramolecular bonds (the thermodynamically lowest

energy level). When this protein is heated, the intramolecular bonds are broken and it denatures

to one of several preferred lower energy states from which it will not spontaneously return to the

native conformation. Conceivably, if the primary structure of the protein is undamaged it may be

plausible to reconfigure the protein using chaperone-assisted mechanisms similar to those which

establish its initial folding after biosynthesis. The second possibility occurs when the native

folded state of the protein is the same as the most energetically preferred conformation in the

absence of intramolecular crosslinks. In this case, the protein is able to spontaneously refold to

its native state.

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The speed of the transition from natural to denatured states is governed by the Arrhenius rate

equation which states that when the kinetic energy of the molecule exceeds a threshold

magnitude Eia (for activation energy), the transition to the ith state will occur (in this case from

natural to denatured state). For a large number of molecules at temperature T the fraction Γ with

a kinetic energy above Ea is governed by the Maxwell-Boltzmann relation (65),

Γi = exp(-Eia / kBT) (4)

where kB is Boltzmann's constant. Because the strength of bonds retaining the folding

conformation of macromolecules is dependent on the nature of the chemical bond, the value of

Eia is dependent on molecular structure. Despite this complexity the net rate of denaturation of

cellular structures containing many different proteins is also often describable in terms of

Equation 4. For example, the accuracy of this equation in describing thermal damage to cell

membranes has been reported to be reasonable (74–76). Even the thermal injury to intact tissues

like human skin is reasonably described by the simple Equation 4. It has been known for more

than 50 years that the rate at which damage accumulates in heated skin can be estimated by

convolving Equation 4 with the temperature history. The resulting expression is called the "heat

damage" equation (77),

d / dt = A (5)

where Ω is a parameter reflective of the extent of damage, and A is a frequency factor that

describes how often a configuration from which reaction is energetically possible occurs, which

is also dependent on molecular structure. The shape of the temperature-time curve predicted by

Equation 5 is the same as the human skin temperature vs. time scald burn curve measured by

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Henriques and Moritz (78). This temperature-time curve shape has also been obtained for heat

damage to isolated cells (76).

Because the lipid bilayer components of the cell membranes are held together only by forces of

hydration, the lipid bilayer is the most vulnerable to heat damage (79). Even at temperatures of

only 6°C above normal (i.e. 43°C) the structural integrity of the lipid bilayer is lost (80). In

effect, the warmed lipid bilayer goes into solution, rendering the membrane freely permeable to

small ions. At slightly higher temperatures, published reports indicate that the contractile

mechanism of muscle cells is destroyed immediately following exposure to 45°C and above (81).

Experiments on fibroblasts demonstrated that heat-induced membrane permeabilization also

begins to appear above 45°C (82).

Bischof et al investigated the effect of supraphysiological temperatures on isolated rat muscle

cells using a thermally controlled microperfusion stage (83). Cells were loaded with the

membrane permeable fluorescent dye precursor calcein-AM. After entering the cell, the

precursor is converted by nonspecific esterases into the membrane impermeable fluorescent

Calcein. Using quantitative fluorescent microscopy, these authors measured time-resolved dye

leakage from the muscle cells at several supraphysiological temperatures. In addition, using

Equations 4 and 5, the authors determined the activation energy necessary to thermally induce

membrane permeabilization in the isolated muscle cells to be 32.9 kcal mol-1 (83). Reported

activation energy values for thermal damage in other cell types are in the range from

30 – 140 kcal mol-1 (76).

Figure 2 illustrates the difference between electroporation damage and thermal damage. Panel A

shows the development of electrical lysis of cells in the muscle caused by a model shock (18). In

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this case, a 0.5 s, 4.5 kV alternating current shock was applied between the palm and the

shoulder, modeling a worst-case scenario 10 kV shock between the hands. Panel B shows the

thermal injury function Ω resulting from a similar 1 s model shock. Joule heating is highest in the

regions of highest current density. These are the regions where the current is constrained to a

smaller cross section area. The most notable such regions are the wrist and the point of electrical

contact (the palm in this case). Figure 2 shows the difference between electroporation and

thermal damage: regions that show no thermal damage can show electroporation damage, and

regions that show significant thermal damage can show little to no electroporation injury. It is

important to point out that a thermal injury function value Ω=1 in a given region does not

correspond to thermal injury of all cells in that region. Ω can take on any positive value.

Specifically, Ω=1 corresponds to approximately 63% of cells being thermally damaged.

Figure 2. Typical electric injury pattern of an electrical shock in a human arm. (A) Injury due to

electrical lysis of muscle cells after a 0.5 s shock. Reprinted from (18) with permission (© 2011

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IEEE). (B) Thermal injury function Ω due to joule heating after a 1 s shock. Thermal damage is

highest at the point of electrical in the palm and the wrist (red), due to lower cross sections

increasing the local current density. Note that the two damage scales are not directly comparable,

because a value of Ω=1 does not correspond to injury of all cells in that volume.

Electro-conformational Denaturation of Transmembrane Proteins Imposed supraphysiologic transmembrane potential differences can produce

electroconformational changes of membrane proteins, ion channels, and ion pumps.

Approximately 30% of cell membrane consists of proteins, some of them embedded into the

bilayer, others spanning across the entire membrane. Many of them carry electric charges from

amino acids with acidic or basic side groups that can be acted on directly by an intense Vm

(charge separation or charge induction through dissociation). In addition, each amino acid has an

electrical dipole moment of about 3.5 D (1 Debye = 3.336×10-30 C m) giving the proteins an

overall dipole moment that, in the case of an -helical protein structure, can reach 120 D (84). In

a strong external electric field those molecules will orient themselves and thereby change their

conformation to increase the effective dipole moment in the direction of that field.

If the field strength becomes sufficiently intense, those field-induced changes can cause

irreversible damage to membrane proteins. In particular ion channels and pumps with their

selective voltage-gated charge transport mechanisms (e.g., Ca2+ specific channel) are highly

sensitive to differences in Vm. Chen et al. investigated the effects of large magnitude Vm pulses

on voltage-gated Na+ and K+ channel behavior in frog skeletal muscle membrane using a

modified double vaseline-gap voltage clamp. They found in both channel types, but more

drastically in K+ channels, reductions of channel conductance and ionic selectivity by the

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imposed Vm (37). Further, these authors were able to demonstrate that these changes are not

caused by the field-induced channel currents (Joule heating damage) but rather by the magnitude

and polarity of the imposed Vm (85). In the most recent work, Clausen et al. (86) studied the

effects of shock and electroporation on the acute loss of force in skeletal muscles and the role of

the Na+ and K+ pumps in the force recovery after electroporation. Ionic pumps alone are

sufficient to compensate a simple mechanical leakage. They report that electroporation induces

reversible depolarization, partial rundown of Na+, K+ gradients, cell membrane leakage and loss

of force. The consequences of this effect may underlie the transient nerve and muscle paralysis in

electrical injury victims.

Radiofrequency (RF) and Microwave Burns

Every year a few cases of RF (radio frequency) or microwave field injuries require medical

attention in the United States. The victims are usually industrial workers. Above the low

frequency regime (>10 kHz), tissue response strongly depends upon the field frequency. In the

10 - 100 MHz RF range, two types of tissue heating occur, Joule and dielectric heating, with

Joule heating outweighing dielectric heating. Small molecules like water, when not bound, are

able to follow the field up to the gigahertz range (87). However, at microwave frequencies

(100 MHz - 100 GHz), dielectric heating is more significant than Joule heating because both

bound and free water is excited by microwave radiation. Molecular dipoles of macromolecules

have lower natural frequencies, so that their most efficient induction frequency is in the

radiofrequency range.

Exposure to ambient microwave fields is known to cause burn trauma. Microwave burns have

different clinical manifestations than low frequency electrical shocks (88–91). At low frequency,

22

the epidermis is a highly resistive barrier, whereas in the microwave regime, electrical power

readily passes the epidermis in the form of capacitive coupling with very little energy

dissipation. Consequently, the epidermis may not be burned unless it is very moist. The

microwave field penetration into tissue has a characteristic depth in the range of 1 cm, resulting

in direct heating of sub-epidermal tissue water. The rate of tissue heating is dependent not only

on the amplitude of tissue electric field, but also on the density of dipoles. For example,

microwave heating is much slower in fatty tissues (91,92).

Lightning Injury

Lightning arcs result from dielectric breakdown in air caused by buildup of free electrical

charges on the surface of clouds. The current through an arc can be enormous, but the duration is

quite brief (1 - 10 ms). The primary current is confined to the surface of conducting objects

connected by the arc. Peak lightning current range between 30,000 - 50,000 A, which is able to

generate temperatures near 30,000 K. This abrupt heating generates a high-pressure

thermoacoustic blast wave known as thunder.

An individual directly struck by lightning will experience current for a brief period of time.

Initially, the surface of the body is charged by the high electric field in the air. This can cause

breakdown of the epidermis, and several hundred amperes to flow through the body for a

1 - 10 µs period, which is long enough to induce electroporation. Following this, a much smaller

current persists for several milliseconds, in which time the body is discharging into the ground.

The duration of current flow is relatively short, so there is no substantial heating except a

breakdown of the epidermis. However, disruption of cell membrane can wreak havoc on nerve

and muscle tissues.

23

When lightning reaches the ground, it spreads out radially from the contact point. A substantial

shock current can be experienced by a person walking nearby, if their feet are widely separated.

For example, with an average lightning current of 20,000 A, a step length of 50 cm, and an

individual located 10 m away from strike point, the voltage drops between the legs can reach

1500 V. This can induce a 2 - 3 A current flow through the body between the legs for a 10 µs

period.

Common Clinical Syndromes Following Electrical Injury

Clinical manifestations of electrical shock depend on the magnitude, frequency and duration of

the imposed fields within the tissues that exist in the current path through the body. It is no

surprise that workers coming in contact with high energy industrial electrical power sources

experience rapid Joule heating of tissues throughout the current path. Total thermal destruction

of tissues throughout the current path can result. Because of the high heat capacity of water,

thermal injury dynamics accrue on a time frame of seconds in most cases. With more rapid

kinetics, electroporation of tissues, especially skeletal muscle and peripheral nerve can occur.

Brief accidental electrical shocks involving several hundred volts are common among

electricians and others working with electrical power. This may not result in a large thermal burn

but will result in neuromuscular dysfunction and pain. Electroporation is the most likely

pathophysiologic process linking the neuromuscular dysfunction to the electrical shock. Acute

symptoms most often resolve in a few days. However, many of these shock victims will develop

late generalized musculoskeletal pain, loss of balance control, and neuropsychological

symptoms. Although the precise mechanisms linking a local brief electrical shock to generalized

24

peripheral and central neurological problems remains under investigation, it is clear that this

sequalae is common (93–96).

The most common anatomical contact point with of electrical current is to the arm and hand.

Regarding the pattern of thermal injury, Joule heating is mostly concentrated at the wrist because

of the small cross-sectional area and the lower conductivity of skin and bone. The second skin

burn wound is usually at the flexor aspect of the elbow, and the third at the armpit. As the energy

decreases along the arm, so does the damage. The skin burn wound varies depending on the

condition of the victim when the incident happens. Where the skin is burned along the current

path, the deeper tissues are as well. Patients can suffer from long term rarefaction of bone and

protracted residual wounds for months to years after recovery.

Electrical injury causes damage to the peripheral nerves and spinal cord, which can lead to

cognitive and emotional changes. Patients exhibit lower attention, verbal memory, learning

ability, and executive function, while experiencing higher incidents of depression and poor anger

control. Research shows the relationship with changes in both cerebra and cognitive circuits, for

example including hypermetabolism in the cerebellum-limbic system.

Diagnostic Imaging of Electrical Injury

Because most of the damage caused by electrical shock occurs beneath the skin, it is important to

discuss how to achieve tissue injury detection and localization. There are two basic cellular

abnormalities in electrical injury: altered protein structure and disrupted cell membranes. In

addition, there can be blood coagulation, tissue edema, elevated tissue pressures and other

25

abnormalities that affect molecular transport. From the clinical perspective, it is important to

recognize areas of damaged cells and interrupted blood flow.

Magnetic resonance imaging (MRI) methods are particularly well suited for detection of changes

in protein folding, disruption of cell membranes and tissue edema. Most useful are MRI methods

based upon measurement of water proton behavior. Since water behavior will change in the

presence of denatured proteins, and osmotic swelling will follow disruption of cell membranes,

the typical MRI equipment in hospitals can measure these changes associated with electrical

injury.

Technetium99m-PYP (pyrophosphate) is widely used as a radiolabel tracer for various forms of

soft tissue injury including electrical trauma because it is believed to follow the calcium

movement in cellular function (97). Increased tracer accumulation in muscle tissue indicates loss

of cell membrane integrity, tissue edema and is predictive of tissue injury. The in vivo rat hind

limb electrical injury model described by Block et al. monitored the uptake of Tc99m-PYP in the

electrically shocked tissue as a function of the magnitude of DC current (27). Either 0.5, 1.0 or

1.85 A of direct current was applied to the rat’s hind limb, and compared to intravenous saline

infusions as the sham-treatment. Their results indicated that Tc99m-PYP does accumulate in

electroporated tissue and the level of the tracer accumulation is positively correlated to the tissue

field pulses applied. This indicates that quantitative imaging of Tc99m-PYP uptake may be

developed further as an indicator of the extent of electroporation or other membrane injury.

A recent report by Park et al. measured cerebral blood volume (CBV) of electrical injury patients

(98). In that study, electric injury patients exhibiting cognitive dysfunction were imaged to

measure CBV. It was found that greater CBV correlated with various clinical measures of

26

cognitive function. Because CBV can be measured with gadolinium contrast enhanced MRI, this

may allow more quantitative means of diagnosing electrical injury and the concomitant cognitive

impairment, as well as leading to more effective treatment.

Summary and Conclusions

Given the importance of electrical power to human culture, the problem of electrical injury is one

that will continue to exist for the foreseeable future. Electrical injury has been poorly understood

and less than optimally managed in the past. Better understanding of injury mechanisms,

anatomical patterns of injury, and therapy are required. A prompt, accurate clinical diagnosis of

electrical injury is one of the most difficult tasks in the medical field (6) because it usually calls

upon an understanding of the complex interactions between the electric current and human

tissue. Specifically an accurate and complete diagnosis is complicated by:

1. The exact tissue damage mechanism and damage level, which depend on a host of

parameters including the characteristics of the power source (DC or AC current, voltage,

frequency, etc.), path and duration of the closed circuit, area and impedance of the contact

spot. Correspondingly, there is a whole spectrum of damage characteristics depending on the

values of these parameters. The physician needs to do 4-dimensional (spatial plus temporal)

detective work in order to arrive at a correct diagnosis.

2. Electrical damage to the tissues is not easily detectable by visual inspection or physical

examination. Often sequelae will not manifest themselves for a while: electrically injured

tissue may initially appear viable, only to become visibly necrotic at a later point (in a

number of days) (99–101).

27

The molecular structure of biological systems can be severely altered by the effects of high-

energy commercial frequency electrical power. The mechanisms of damage include cell

membrane electroporation, Joule heating, and electroconformational changes (denaturation) of

proteins and other macromolecules. Rehabilitation and reconstruction needs in the electrically

injured are usually not obvious at the initial evaluation. The reintegration of the individual into

their pre-injury living situation often becomes a real challenge. Aside from physically obvious

impairments (loss of limb etc.) it is not uncommon for an electrician to develop a phobia towards

electricity after being injured. The more in-depth understanding of the underlying mechanism of

injury will lead to a more specific treatment regime that may prevent some of the late sequelae of

electrical injury.

Acknowledgements

Parts of the research presented were funded by grants from the Electric Power Research Institute

(RP WO-2914 and RP WO-9038), the National Institutes of Health (NIGMS 5-R01 GM53113)

and Commonwealth Edison. The authors thank Zhou-xian Pan for assistance in editing this

chapter.

28

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