It is thought that the primary mechanism of cell death from IRE is apoptosis (programmed cell death), in contrast to coagulative necrosis (death by ischemia or infarction), which is the primary mechanism in radiofrequency and microwave ablation. However, the exact molecular mechanism of cell death after IRE is unknown, and both necrosis and apoptosis are likely to occur. Initially,it was thought that the poration of the membrane, which leads to increased permeability, was the primary trigger of cell death.
After the application of the electric field, the enhanced transmembrane molecular transport with rapid membrane discharge induces the cell to attempt to recover its membrane potential by conducting small ions, including sodium and chloride, through the transient pores. Cells under extensive chemical or osmotic stress from excessive molecular transport may then undergo lysis. Additionally, if one or more critical pores expand, the membrane may be destroyed, leading to complete dissolution of the cell.
Newer studies have shown that apoptosis after the application of electrical fields can occur without pore formation,although when pores are induced,apoptotic markers appear faster. Short electrical pulses induce an intracellular calcium release, most likely by the poration of the endoplasmic reticulum membrane, which in turn may initiate apoptosis. Electrical pulses may also increase the mitochondrial permeability, releasing cytochromec, which is a small protein involved in the initiation of apoptosis. Finally,electric pulses may cause DNA damage and elevated levels of reactive oxygen species, inducing oxidative stress-mediated apoptosis.Reports on the pathways that lead to cell death are contradictory. For instance,one study reported extensive caspase-3 activation 24 hours after the IRE of rat hepatocellular carcinoma,suggesting apoptosis , while another did not detect any caspase-3 positive cells in the treated area of pancreatic carcinoma . Contradictory reports may reflect differences in the tumor model used, among other experimental factors.
In summary, the proposed mechanisms of apoptotic cell death due to IRE include cell rupture from pore expansion and osmotic/chemical stress, intracellular calcium release from the endoplasmic reticulum, cytochromec release from mitochondria, and oxidative stress. Irreversibly permeabilized cells that undergo apoptosis are then removed by the immune system, and the IRE may potentiate an immune reaction to the ablated tissue, enhancing the treatment effect.
來源：Irreversible electroporation: evolution of a laboratory technique in interventional oncology
(Diagn Interv Radiol 2014; 20: 147-154) DOI: 10.5152/dir.2013.13304