Tissue Ablation by Rapid and Sustained Alteration in Membrane Potential (TARSAMP)
TARSAMP is a method for the ablation of undesirable tissue, such as cells of a cancerous or non-cancerous tumor, infected tissue, adipose tissue, wound, etc., comprising the injection of at least one ion channel blocker and/or ion pump blocker into said undesirable tissue then applying a low voltage electrical current (alternatively, ultrasound or osmotic pressure) into said undesirable tissue to trigger a rapid and sustained change in membrane potential (Vm) of the targeted cells, causing said undesirable tissue to die by a process of programmed cell death (apoptosis) followed by immune system action on any surviving or recurring cells of the undesirable tissue.
BACKGROUND OF THE INVENTION
- Field of the Invention
The present invention relates to tissue ablation devices and methods, particularly the ablation of undesirable tissue, such as a cancerous or non-cancerous tumor, infected tissue, adipose tissue, wound, etc.
- Brief Discussion of the Related Art
Each cell in the human body has a potential difference with its extracellular milieu owing to a difference in the concentrations of the main physiological ions (Na+, K+, Ca2+, and Cl–) between the cell and the extracellular milieu. The potential difference can be measured across the plasma membrane and represents the membrane potential (Vm) of the cell. Vm changes in response to a change in conductance (or permeability) of one or more of the major ion types, and also depends on the concentrations of the major ions inside the cell and in the extracellular milieu, as shown in the Goldman–Hodgkin–Katz equation below (Goldman, 1943; Hodgkin and Katz, 1949):
Vm = RT/F ln ((PNa+ [Na+]o + PK+ [K+]o + PCl− [Cl−]o) / (PNa+ [Na+]i + PK+ [K+]i + PCl− [Cl−]i))
where R is the ideal gas constant, T is the temperature, and F is the Faraday constant. The role of Vm is different in excitable and non-excitable cells.
Excitable cells, such as neurons and muscle fibers, function primarily by rapid changes in Vm that are followed by an immediate return to the resting Vm. The role of Vm in non-excitable cells is not as clear. There is, however, an increasing body of knowledge that suggests that Vm may have important regulatory roles in non-excitable cells.
It is known that different tissues have different resting Vm values, and abnormal tissues, such as cancer and wounds, have Vm values that are vastly different from those of the corresponding normal tissues. The Vm of adipose tissue is also vastly different from those of normal tissues. Some examples of the differences in Vm between normal and abnormal tissues include the following:
- The Vm of cells in proliferating breast cancer is more depolarized than cells in normal breast tissue (Marino et al., 1994);
- The Vm of proliferating hepatocellular carcinoma cells is more depolarized than normal hepatocytes (Binggeli and Cameron, 1980; Stevenson et al., 1989);
- The Vm of cells in proliferating, neoplastic adrenocortical tissue is more depolarized than cells in normal adrenocortical tissue (Lymangrover et al., 1975);
- The Vm of proliferating fibrosarcoma cells is more depolarized than normal fibroblasts (Binggeli and Weinstein, 1985);
- The Vm of cells in proliferating skin cancer is more depolarized than benign skin cells (Melczer and Kiss, 1957; Woodrough et al., 1975);
- The Vm of cells in proliferating ovarian cancer cells is more depolarized than normal ovarian cells (Redmann et al., 1972); and
- The Vm of adipocytes, at 34 mV, is significantly more depolarized than other cells in normal human tissue (Al-Hilli and Willander, 2009).