title: Low-frequency sonophoresis: pathologic and thermal effects in dogs.
abstract: OBJECTIVE
  Low-frequency sonophoresis has recently been shown to significantly facilitate transdermal permeability of various substances (e.g., insulin) in animal models, thus eliminating the need to inject such agents. Prior to human trials, the authors studied the safety profile of low-frequency sonophoresis in dogs by evaluating microscopic and temperature changes in the skin after sonophoresis.
  
  
  METHODS
  An evaluator-blinded canine study of sonophoresis using different energy intensities 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 KHz with a maximal energy output of 400 W. The sonicator was immersed in normal saline, and intensities of 4%, 10%, 20%, 30%, and 50% were applied during 600 msec of every second (pulsed mode). Three probes, 1-cm cylindrical, 5-cm cylindrical, and 10-cm disc-shaped, were evaluated. Each experimental condition was performed twice. Subcutaneous temperatures were measured by temperature probe before and after sonophoresis. At 30 minutes post-sonophoresis, full-thickness skin biopsies were taken for blinded histopathologic evaluation.
  
  
  RESULTS
  Minimal urticarial reactions were noted with the 1-cm probe at intensities of < or = 20% and with the 5-cm probe at 4% intensity. With higher intensity, thermal injuries were observed grossly with erythema and vesicles. The microscopic correlates were papillary and dermal edema with neutrophils and telangiectasia. The conditions producing vesicles grossly had foci of epidermal necrosis, subepidermal vesicles, and degeneration 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-intensity conditions resulted in second-degree burns, most likely attributable to localized heating.
authors.affiliation: Department of Emergency Medicine, State University of New York, University Medical Center, Stony Brook, NY, USA. asinger@epo.som.sunysb.edu
authors.forename: A J
authors.initials: AJ
authors.lastname: Singer
authors.forename: C S
authors.initials: CS
authors.lastname: Homan
authors.forename: A L
authors.initials: AL
authors.lastname: Church
authors.forename: S A
authors.initials: SA
authors.lastname: McClain
mesh_terms: D000279:Administration, Cutaneous; D000704:Analysis of Variance; D000818:Animals; D002056:Burns / Q000209:etiology*; D004285:Dogs; D015612:Phonophoresis / Q000009:adverse effects*; D011446:Prospective Studies; D012867:Skin / Q000473:pathology*; D012881:Skin Temperature; D014581:Urticaria / Q000209:etiology*