Optimization of enhancement of therapeutic efficacy of ultrasound: Frequency-dependent effects on iodine formation from KI-starch solutions and ultrasound-induced killing of rat thymocytes.

We investigated liberation of iodine from solutions of KI-starch and cell lysis of rat thymocytes in argon-and nitrous oxide-saturated aqueous solutions induced by ultrasound at frequencies of 38 and 500 kHz and 1 and 2 MHz. Iodine was liberated in argon-saturated solutions exposed to ultrasound at 38 kHz, 500 kHz, and 1 MHz but not at 2 MHz. Lysis occurred in argon-saturated solutions at all four frequencies, but only at 38 kHz in nitrous oxide-saturated cell suspensions. No iodine was liberated in the other nitrous oxide-saturated samples. Relative ratio of the chemical effect versus 70-percent cell survival (an example of the physical effect) was, in order of frequency, 500 kHz>1.0 MHz>38 kHz>2.0 MHz. Partial protection was observed for cell lysis and cell viability after sonication with 500 kHz in argon-saturated solution containing cysteamine, a free radical scavenger. These results suggest that the chemical effects of ultrasound are prominent at specific frequencies, and that free radicals induced by ultrasonic cavitation partially affect lysis and the loss of viability of rat thymocytes.