The interphase interval within a bipolar nanosecond electric pulse modulates bipolar cancellation.

Nanosecond electric pulse (nsEP) exposure generates an array of physiological effects. The extent of these effects is impacted by whether the nsEP is a unipolar (UP) or bipolar (BP) exposure. A 600 ns pulse can generate 71% more YO-PRO-1 uptake compared to a 600 ns + 600 ns pulse exposure. This observation is termed "bipolar cancellation" (BPC) because despite the BP nsEP consisting of an additional 600 ns pulse, it generates reduced membrane perturbation. BPC is achieved by varying pulse amplitudes, and symmetrical and asymmetric pulse widths. The effect appears to reverse by increasing the interphase interval between symmetric BP pulses, suggesting membrane recovery is a BPC factor. To date, the impact of the interphase interval between asymmetrical BP and other BPC-inducing symmetrical BP nsEPs has not been fully explored. Additionally, interpulse intervals beyond 50 μs have not been explored to understand the impact of time between the BP nsEP phases. Here, we surveyed different interphase intervals among symmetrical and asymmetrical BP nsEPs to monitor their impact on BPC of YO-PRO-1 uptake. We identified that a 10 microsecond (ms) interphase interval within a symmetrical 600 ns + 600 ns, and 900 ns + 900 ns pulse can resolve BPC. Furthermore, the interphase interval to resolve asymmetric BPC from a 300 ns + 900 ns pulse versus 600 ns pulse exposure is greater (<10 ms) compared to symmetrical BP nsEPs. From these findings, we extended on our conceptual model that BPC is balanced by localized charging and discharging events across the membrane. Bioelectromagnetics. 39:441-450, 2018. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.