LOW-FREQUENCY SONOPHORESIS - PATHOLOGICAL AND THERMAL EFFECTS IN DOGS

Objective: Low-frequency sonophoresis has recently been shown to signi ficantly facilitate transdermal permeability of various substances (e. g., insulin) in animal models, thus eliminating the need to inject suc h agents. Prior to human trials, the authors studied the safety profil e of low-frequency sonophoresis in dogs by evaluating microscopic and temperature changes in the skin after sonophoresis. Methods: An evalua tor-blinded canine study of sonophoresis using different energy intens ities and probe diameters was performed. Low-frequency ultrasound was applied for 60 seconds to the clipped abdominal skin of 3 anesthetized adult mongrel dogs using a sonicator operating at a frequency of 20 K Hz with a maximal energy output of 400 W. The sonicator was immersed i n normal saline, and intensities of 4%, 10%, 20%, 30%, and 50% were ap plied during 600 msec of every second (pulsed mode), Three probes, l-c m cylindrical, 5-cm cylindrical, and 10-cm disc-shaped, were evaluated . Each experimental condition was performed twice. Subcutaneous temper atures were measured by temperature probe before and after sonophoresi s. At 30 minutes post-sonophoresis, full-thickness skin biopsies were taken for blinded histopathologic evaluation. Results: Minimal urticar ial reactions were noted with the 1-cm probe at intensities of less th an or equal to 20% and with the 5-cm probe at 4% intensity. With highe r intensity, thermal injuries were observed grossly with erythema and vesicles. The microscopic correlates were papillary and dermal edema w ith neutrophils and telangiectasia, The conditions producing vesicles grossly had foci of epidermal necrosis, subepidermal vesicles, and deg eneration of papillary dermal collagen. With still higher intensities, confluent epidermal necrosis became apparent. Use of the 10-cm probe did not result in any injury, Conclusions: Low-frequency ultrasound at low intensities appears safe for use to enhance the topical delivery of medications, producing only minimal urticarial reactions. Higher-in tensity conditions resulted in second-degree burns, most likely attrib utable to localized heating.