Pharmacologic inhibition of collagen in an experimental model of subglottic stenosis.
Subglottic stenosis occurs as a complication of prolonged endotracheal intubation secondary to inflammation with development of scar tissue and subsequent fibrosis. Collagen I and III levels increase during the healing process. Steroids alter the inflammatory response, decreasing recruitment of macrophages and fibroblasts. Beta-aminopropionitrile (betaAPN) inhibits the development of collagen cross-linking. A mechanism that would minimize hypertrophic scarring was sought. Eighteen dogs were anesthetized, had tracheostomies performed, and later had cautery of the mucosa and inner layer of the cricoid cartilage. Of 18 survivors, 6 animals were used as controls, 6 animals received oral Decadron, 2 mg/d, and 6 animals received oral betaAPN, 40 mg/d. There were 9 early deaths--5 in the steroid group. Animals were painlessly sacrificed, and the specimens were sectioned at the cricoid cartilage level and were stained immunohistochemically for antibodies to collagen types I to VI. Analysis of the area of scar and the intensity of stain was performed with Mocha image analysis software. Collagen III increased in control animals to 14.38 +/- 1.85 (intensity stain index), but this reaction was reduced by betaAPN (5.77 +/- 1.78, p < .01). Steroids had no significant effect on formation of any type of collagen. Lathyrogens (betaAPN) may offer a pharmacologic tool to reduce scar tissue.
Doolin
E J
EJ
Department of Surgery, Robert Wood Johnson Medical School at Camden, New Jersey, USA.
Tsuno
K
K
Strande
L F
LF
Santos
M C
MC
D000629:Aminopropionitrile / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002921:Cicatrix / Q000473:pathology; D003094:Collagen / Q000037:antagonists & inhibitors*; D003907:Dexamethasone / Q000494:pharmacology*; D004285:Dogs; D005931:Glottis; D007150:Immunohistochemistry; D007829:Laryngostenosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D000629:Aminopropionitrile; D003907:Dexamethasone; D003094:Collagen