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Electromagnetic Fields in Biological Systems
(Pakhomov et al. 2006). The facilitation could be the result of calcium release from
internal stores followed by biochemical reactions involving troponin (Wexler, Ding,
and Binder-Macleod 1997). Inhibition at higher fields, on the other hand, could be due
to localized nerve membrane poration. With localized poration, the outer membrane
could have the effect of attenuating voltage waves traveling down the neurons. More
recently, Despa et al. (2009) showed electromuscular effects linked to direct nerve excitation by external electric fields. A common theme in their observations seems to be that
neuromuscular bioresponses can be stimulated or modulated by direct electrical pulsing
at remote sites.
2.4 Temperature Changes Due to Electric Pulsing
In dealing with in vivo biological tissues exposed to an electric field, it is important to
consider the SAR and AD because these quantities influence the biological outcomes.
More importantly, perhaps, the temperature rise associated with Joule heating is an
important indicator because most internal processes are energy driven. The severity of
this temperature rise is dependent on the electric pulse input parameters and tissue electrical properties. In some cases, such as electrochemotherapy, pulse parameters are deliberately chosen to ensure negligible changes in temperature with complete reversibility.
Electrochemotherapy incorporates electroporation with chemotherapeutic drugs
such as bleomycin and has been shown to be an effective technique in treating tumors
in vivo (Gothelf, Mir, and Gehl 2003; Heller, Gilbert, and Jaroszeski 1999). Clinical electroporation pulse parameters are typically short (∼100 μs), with fields in the 1–2 kV/cm
range with pulse repetition rates of 1 Hz (Belehradek et al. 1993; Rols et al. 2000). Due to
the relatively short-pulse durations of these “electroporation pulses,” the resulting temperature increases and associated thermal damage to the tissue are generally negligible.
For large molecule electroporation such as electrogene and DNA transfer, longer pulses
are required to utilize electrophoretic effects (Rols and Teissie 1998; Mir et al. 1999).
Pulse parameters in such cases may result in noticeable tissue heating. An in vivo study
of electrogene transfer conducted on rat liver cells (Suzuki et al. 1998) has shown that the
highest rate of gene transfer occurs at locations on the border between the necrotized and
surviving cells. It has also been shown (Muramatsu, Nakamura, and Park 1998) that the
amount of gene transfer is strongly tied to the amount of heat generated, below the threshold of tissue damage. Another innovative application of electroporation has been proposed
(Davalos, Mir, and Rubinsky 2005), in which irreversible electroporation (requiring longer,
more intense pulses than reversible electroporation) is used to induce nonthermal killing
of cancerous tissue. In that study, a numerical study was conducted exploring electroporation parameters that maximized irreversible electroporation (while minimizing thermal
damage) in order to isolate cell killing by electroporation from cell killing by heating.
The temperature distribution in the context of in vivo electroporation is affected by
several factors such as the presence of a blood vessel, external convective influences,
metabolic heat generation, perfusion influences, and electrode geometry or spacing.
Given the experimental difficulties of obtaining both spatially and temporally resolved
data on heating, these issues have often been probed through simulations. For example, Davalos, Rubinsky, and Mir (2003) have implemented one- and two-dimensional
Electromagnetic Fields in Biological Systems
(Pakhomov et al. 2006). The facilitation could be the result of calcium release from
internal stores followed by biochemical reactions involving troponin (Wexler, Ding,
and Binder-Macleod 1997). Inhibition at higher fields, on the other hand, could be due
to localized nerve membrane poration. With localized poration, the outer membrane
could have the effect of attenuating voltage waves traveling down the neurons. More
recently, Despa et al. (2009) showed electromuscular effects linked to direct nerve excitation by external electric fields. A common theme in their observations seems to be that
neuromuscular bioresponses can be stimulated or modulated by direct electrical pulsing
at remote sites.
2.4 Temperature Changes Due to Electric Pulsing
In dealing with in vivo biological tissues exposed to an electric field, it is important to
consider the SAR and AD because these quantities influence the biological outcomes.
More importantly, perhaps, the temperature rise associated with Joule heating is an
important indicator because most internal processes are energy driven. The severity of
this temperature rise is dependent on the electric pulse input parameters and tissue electrical properties. In some cases, such as electrochemotherapy, pulse parameters are deliberately chosen to ensure negligible changes in temperature with complete reversibility.
Electrochemotherapy incorporates electroporation with chemotherapeutic drugs
such as bleomycin and has been shown to be an effective technique in treating tumors
in vivo (Gothelf, Mir, and Gehl 2003; Heller, Gilbert, and Jaroszeski 1999). Clinical electroporation pulse parameters are typically short (∼100 μs), with fields in the 1–2 kV/cm
range with pulse repetition rates of 1 Hz (Belehradek et al. 1993; Rols et al. 2000). Due to
the relatively short-pulse durations of these “electroporation pulses,” the resulting temperature increases and associated thermal damage to the tissue are generally negligible.
For large molecule electroporation such as electrogene and DNA transfer, longer pulses
are required to utilize electrophoretic effects (Rols and Teissie 1998; Mir et al. 1999).
Pulse parameters in such cases may result in noticeable tissue heating. An in vivo study
of electrogene transfer conducted on rat liver cells (Suzuki et al. 1998) has shown that the
highest rate of gene transfer occurs at locations on the border between the necrotized and
surviving cells. It has also been shown (Muramatsu, Nakamura, and Park 1998) that the
amount of gene transfer is strongly tied to the amount of heat generated, below the threshold of tissue damage. Another innovative application of electroporation has been proposed
(Davalos, Mir, and Rubinsky 2005), in which irreversible electroporation (requiring longer,
more intense pulses than reversible electroporation) is used to induce nonthermal killing
of cancerous tissue. In that study, a numerical study was conducted exploring electroporation parameters that maximized irreversible electroporation (while minimizing thermal
damage) in order to isolate cell killing by electroporation from cell killing by heating.
The temperature distribution in the context of in vivo electroporation is affected by
several factors such as the presence of a blood vessel, external convective influences,
metabolic heat generation, perfusion influences, and electrode geometry or spacing.
Given the experimental difficulties of obtaining both spatially and temporally resolved
data on heating, these issues have often been probed through simulations. For example, Davalos, Rubinsky, and Mir (2003) have implemented one- and two-dimensional