Biomechanical monitoring of cutaneous sulfur mustard-induced lesions in the weanling pig model for depth of injury.
OBJECTIVE
A sulfur mustard (SM)-induced cutaneous injury model was developed in weanling swine to evaluate the efficacy of candidate treatment regimens. Lesions were assessed clinically and histopathologically. Histopathologic evaluation of lesions was a subjective and invasive assessment. Biomechanical engineering methods offer an objective and less invasive method to evaluate lesions. The purpose of this study was to use biomechanical engineering instruments to assess SM-induced lesions for depth of injury and to correlate those assessments with histopathology.


METHODS
Two groups of six animals each were exposed to 400 microL undiluted SM applied at each of six abdominal sites for either 2 or 30 min. An additional seven animals received a sham treatment (control; 400 microL deionized water applied to each of six sites for 30 min). Each site was evaluated before exposure and 2 days after exposure. Biomechanical engineering techniques used to assess each lesion were reflectance colorimetry, evaporimetry [transepidermal water loss (TEWL)], laser Doppler perfusion imaging, and high-frequency (20 MHz) two-dimensional ultrasound. Injury depth and lesion severity were assessed and correlated to biomechanical methods using special histopathologic staining techniques.


RESULTS
Two- and 30-min cutaneous lesions were significantly different from controls at the 0.05 probability level for redness (chroma meter) and TEWL (evaporimeter), but were not significantly different from each other. The 2-min lesions had a significant increase (2.11 AU, SE=0.06) and the 30-min lesions had a decrease (0.96 AU, SE=0.04) from controls (1.31 AU, SE=0.03) in microcirculatory blood flux (laser Doppler). The 2-min lesions and controls were significantly different at the 0.05 level from 30-min lesions in skin thickness (ultrasound). The 2- and 30-min groups were significantly different from controls and from each other at the 0.05 level in histopathologic assessment of injury depth, basal cell necrosis, depth of necrosis, and vascular necrosis, with the 30-min injuries being most severe.


CONCLUSIONS
There was mixed evidence that the bioengineering techniques tested could differentiate between controls, 2-min (partial-thickness) cutaneous injuries and 30-min (full-thickness) cutaneous injuries at day 2. Both biomechanical and histopathologic assessments are useful methods of characterizing SM lesions in the weanling pig model. Biomechanical methods are non-invasive and quantitative, and multiple readings over shorter and longer periods of time may improve differentiation in depth of injury. Histopathologic assessments are important for confirmation of lesion depth and severity, and for assisting interpretation when a single assessment using bioengineering methods is used.
Reid
Frances M
FM
Medical Research and Evaluation Facility, Battelle, Columbus, OH, USA. reidf@battelle.org
Niemuth
Nancy A
NA
Shumaker
Shawn M
SM
Waugh
Jack D
JD
Graham
John S
JS
D000818:Animals; D001696:Biomechanical Phenomena / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D009151:Mustard Gas / Q000633:toxicity*; D012720:Severity of Illness Index; D012867:Skin / Q000187:drug effects* / Q000503:physiopathology*; D012871:Skin Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology*; D013552:Swine
D009151:Mustard Gas