Graded carbon dioxide laser-induced subglottic injury in the rabbit model.

OBJECTIVE: To conduct an endoscopic and histologic analysis of the subglottic effects of various carbon dioxide laser-induced injuries in the rabbit model. DESIGN: Animals were assigned to either a control (cricothyroidotomy only) group or 4 (cricothyroidotomy and posterior subglottic laser) groups that were injured using varying systematically controlled carbon dioxide laser power exposures (5 W, 8 W, and 12 W), with durations of 2 or 4 seconds, and surface area exposures (25% or 40%). SUBJECTS: Twenty-seven New Zealand white rabbits. INTERVENTIONS: The subglottis was approached via cricothyroidotomy. Control airways were immediately closed, while injured airways were subjected to graded carbon dioxide laser exposures prior to closure. Airways were endoscopically monitored preoperatively, immediately postoperatively, and on postoperative days 1, 7, 14, and 21, after which the animals were humanely killed and subglottic tissue harvested for histological evaluation. RESULTS: Clinical observation revealed no significantly obstructive (acute) stenosis during the duration of the study. Endoscopic visualization revealed the formation of posterior subglottic scarring. Histological analysis of the mucosa revealed that use of carbon dioxide laser resulted in a statistically significant (unpaired, 2-tailed t test, P<.05) proportional thickening of the lamina propria layer, without significant changes in the epithelial and cartilaginous layers. In addition, mucosal blood vessel size increased proportional to the power of the laser delivered to the area (P<.05). CONCLUSIONS: Carbon dioxide laser-induced injury to the subglottis caused localized scarring, lamina propria thickening, and increased vascularity, which resolved with time and was not associated with significant airway obstruction. This model describes a systematic, controlled, and reproducible method of investigating subglottic injury.

Elucidating the role of interleukin 1beta and prostaglandin E2 in upper airway mucosal wound healing.

OBJECTIVES: To determine whether (1) inflammatory mediators IL-1beta (interleukin 1beta) and prostaglandin E2 (PGE2) in mucosal secretions correlate with subglottic mucosal injury; and (2) mucosal fibroblasts contribute to PGE2 production during mucosal healing. DESIGN: The subglottic mucosa in rabbits was wounded by means of varied carbon dioxide laser power and duration. Subglottic fibroblasts were exposed to IL-1beta and assayed for production of PGE2. SUBJECTS: Thirty-eight New Zealand white rabbits were used. Fibroblasts from normal and pathologic human subglottic tissues were grown in culture. INTERVENTIONS: Subglottic injury was established in 29 rabbits, and 9 rabbits were sham-wounded. Subglottic mucosal secretions were collected at baseline and days 1, 3, 7, 14, and 21 postoperatively and assayed for IL-1beta and PGE2 by enzyme-linked immunosorbent assay. Tissue was analyzed using quantitative polymerase chain reaction. Fibroblast cultures were exposed to IL-1beta and analyzed for PGE2 and its synthetic enzymes. RESULTS: Subglottic injury was associated with increased levels of IL-1beta and PGE2 in secretions. More extensive mucosal injury resulted in higher PGE2 levels at earlier times. Levels of IL-1beta were maximal after lesser damage. Expression of IL-beta and cyclo-oxygenase 2 was elevated after mucosal injury. Fibroblast treatment with IL-1beta resulted in translocation of nuclear factor kappaB, up-regulation of PGE2 synthetic enzymes, and increased production of endogenous PGE2. CONCLUSIONS: Mucosal injury is associated with up-regulation of inflammatory genes and parallel increases in secretion levels of IL-1beta and PGE2, key mediators of inflammation and healing. Subglottic mucosal fibroblasts are a potential source of inflammatory mediators after injury or other trauma.